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Biomedical subjects

L Miravet

Publications and source records attributed to L Miravet.

At least 73 records · Page 4Linked to original sources

Calcium phosphate metabolism and bone disease in patients with homozygous thalassemia.

Calcium and phosphate metabolism were studied in 22 patients with homozygous thalassemia. The overall results showed no significant difference for serum calcium, phosphorus, alkaline phosphatase, immunoreactive parathyroid hormone, or 25-hydroxyvitamin D between thalassemic and control children. However, during the winter, serum 25-hydroxycholecalciferol levels were very significantly decreased in thalassemic children. A study of the hands showed thin metacarpal cortices related to increased resorption. Histomorphometric study of four iliac bone biopsies showed normal osteoclastic resorption and decreased bone formation. Prussian blue staining and x-ray electron microprobe analysis showed iron deposits inside the bone. Whether this finding is critical in the pathogenesis of the bone disease in unknown.

Adolescent↗

[Effects of the dihydroxyl metabolites of vitamin D3 and their ethanol solvent on parathyroid secretion: in vivo study in the rat].

The regulation of parathyroid secretion by the vitamin D3 dihydroxylated metabolites was studied by differents authors. In vitro experiments showed that 1 alpha (OH)2 D3 and 24 R 25 (OH)2 D3 inhibited the PTH release. In Rats maintained in a normal calcium diet or calcium and/or vitamin D deficient diet, 1 alpha 25(OH)2 D3 and 24 R 25 (OH)2 D3 inhibited the PTH release, whereas 24 S 25 (OH)2 D3, 25 S 26 and 25 R 26(OH)2 D3 had no effect.

Animals↗

Action of vitamin D metabolites on PTH secretion in man.

We have examined the effects of metabolites of vitamin D [25OHD3, 1,25(OH)2D3, 24,25(OH)2D3, and 25,26(OH)2D3] on serum calcium and iPTH in human deficient-D osteomalacia. The four metabolites decreased iPTH, but only for 1,25(OH)2D3 was a significant correlation between increase of serum calcium and decrease of iPTH observed. The 24,25(OH)2D3 and 25,26(OH)2D3 decreased iPTH despite a decrease of serum calcium at the beginning of treatment. The 25OHD decreased iPTH before increased serum calcium. These results could be interpreted as a direct effect of metabolites of vitamin D on PTH secretion. However, the conversion of other metabolites and the calcium concentration in parathyroid cells must be determined before this hypothesis can be accepted.

24,25-Dihydroxyvitamin D 3↗

Bone histomorphometric reproducibility in normal patients.

To study bone histomorphometry reproducibility in normal subjects, we performed during orthopedic surgery bone biopsies in 16 postmenopausal women. Each woman had four bone biopsies, two at the usual site in the iliac crest, one on the left and one on the right side, and two other biopsies just behind the usual site, one at each side. We performed measurements of trabecular bone volume, relative osteoid volume, osteoid surfaces, osteoclastic resorption surfaces and calcification front. The average values of the 16 patients were compared, on the one hand, two by two, by a student test, and on the other hand, by a variance analysis. By these two methods the results showed no significant difference between the average values of the 16 patients at each location for any of the histomorphometric parameters studied. However, there was a location variation which was estimated by the intra-individual variation for a given patient. On the other hand, we calculated from the variance analysis the location variance for a group of 10 to 100 patients. In any case all the parameters had a location variation which was high for osteoclastic resorption surfaces and relative osteoid volume when expressed in % of the absolute value of these parameters. The variation of the trabecular bone volume was 0--46. 15% (95% confident limit interval) in a single patient and the hypothetical value of the location variation was 41.6% for a group of 10 patients and 13.0% for a group of 100 patients.

Aged↗

Bone histomorphometry in hemodialysed patients.

We performed bone histomorphometry in thirty hemodialysed patients. Ten patients had a double iliac bone biopsy to estimate bone histomorphometry reproductibility. There was no difference between the mean results for each of the 10 patients at each site. However, there was an intra-individual variation which was small for the parameters of formation and particularly osteoid thickness and mineralizing rate and greater for resorption parameters. Mineralization rate appeared the most reliable and discriminant parameter. These 30 patients were separated in two groups according to their mineralizing rate (MR); patients with an MR greater than 0.3 mu/day were in group I and had severe hyperparathyroidism without major impairment of bone mineralization and high formation rate. They also had high serum alkaline phosphatases and high serum parathyroid levels measured with a COOH terminal antibody (iPTH). Patients with a low MR less than 0.3 mu/day (group II) had a severe mineralization defect with low formation rate, normal alkaline phosphatase and significantly lower levels of iPTH than in group I. This last type of histological bone lesion could not be due to aluminum intoxication since the level of serum aluminum was the same in the two groups. The mineralizing defect appeared to be inversely correlated with the percent of osteoid surfaces covered by osteoblast and with the iPTH level. These data suggest that during the course of renal osteodystrophy PTH stimulates not only bone resorption but also bone mineralization by increasing osteoblastic number.

Adolescent↗

Acute effects of Solanum malacoxylon on bone formation rates in growing rats.

The plant Solanum malacoxylon is responsible for a syndrome of hypercalcemia, soft tissue mineralization, and progressive wasting in South American cattle known as enteque seco or espichamento. There is evidence that a glycoside of 1,25-dihydroxycholecalciferol is the active principle in the plant. The basis for the hyperostosis seen in the disease is unclear. To study the acute effects on bone formation rates, 8-week-old rats were given an aqueous extract equivalent to 250 or 1000 mg of Solanum daily per os for 7 days. Bones were labeled by injection of fluochrome 2 days before the start of treatment and 2 days prior to sacrifice. Morphometric evaluation of undecalcified sections of caudal vertebrae revealed an increased amount of trabecular bone in both Solanum treated groups with no difference due to dose level. This was associated with an increase in the bone apposition rate on trabecular surfaces. No differences were found in the amount of osteoid seam width. Periosteal apposition rate and endochondral bone formation were also measured and no significant differences found. The findings indicate that acute stimulation of cell level bone formation on trabecular surfaces may play a role in the hyperostosis seen in the naturally occurring condition.

Animals↗

[Vitamin D3 sulfoconjugate distribution and evolution in pregnant or lactating rats].

24 hrs after intravenous injection of vitamin D3 35S sulfoconjugate the radioactivity in kidney is about twice as much in pregnant Rats as in lactating Rats. It decreases from 24 to 48 hrs in pregnant but increases in lactating Rats kidneys. Hydrolysis of vitamin 3H D3 sulfate is detected in kidney and liver extracts, the ratio of free vitamin D3 on vitamin D3 sulfate is higher in pregnant than in lactating animals. Mammary glands of lactating Rats contain mainly the unchanged vitamin D3 sulfate which can be hydrolysed by new born suckling pups.

Animals↗

[Magnesium and several metabolic osteopathies].

Magnesium is a constituant of the bone minerals. Changes in its intra-bone distribution have repercussions on the distribution of calcium and on the hormonal regulators of calcium. The importance of magnesium in bone pathology is far from being completely elucidated. Certain factors are now commonly admitted, for example the inhibition of the parathyroid secretion during magnesium deficiency. Others merit more complete and thorough study, it being highly unlikely that the bone is unaffected by changes in the organic magnesium content, given the multiple roles that magnesium plays in the bone. In this report, the authors provide well-known data on the physiology of magnesium, and discuss some of the relationships between magnesium disturbances and certain osteopathies.

Animals↗

[The Solanum molacoxylon: from the toxic plant to the therapeutic agent (author's transl)].

The solanum molacoxylon (SM) is a plant which grows in South America, whose leaves produce a calcinosis on animal farms. In the aquous extract of the leaves a glycoside of 1, 25 (OH)2D3 has been found. The aquous extracts of the leaves of SM provokes an increase of intestinal calcium absorption without any transformation, because it is active in total nephrectomized animal. If this extract is given during a short time the bone resorption is dramatically increased, nevertheless if it is given chronically an increase of bone formation with an osteosclerosis is observed. This plant increases the plasma and urinary calcium and sometimes the plasma phosphorus. In acute administration the urinary hydroxyproline increases. A few therapeutic assays were done in humans with similar results. These assays suggest that SM could be a natural source of 1,25 dihydroxycholecalciferol.

Animals↗

Chromatographic separation of vitamin D3 sulfate and vitamin D3.

This paper describes a simple chromatographic technique on Sephadex LH20 for the separation of vitamin D3 sulfate from free vitamin D3 and its metabolites. This technique has been used in the study of vitamin D3 sulfate metabolism in rats. Seven hours after injection of vitamin D3 sulfate (35S or 35S and 3H) only the peak of vitamin D sulfoconjugate was found in chromatographic elution of serum extracts.

Animals↗

Vitamin D metabolites and bone mineralization in man.

A comparison was made of the biochemical and osseous effects of 25-hydroxyvitamin D3 [25(OH)D3], 1 alpha-25-hydroxyvitamin D3 [1 alpha, 25(OH)2D3], and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] in adult vitamin D-deficient man. Administration of 50 micrograms/d of 25(OH)D3 for 8 weeks led to a return of the mineralization front to normal associated with a return of TmPO4/GFR to normal, an increase in serum phosphate and calcium concentrations, a fall in serum IPTH, and a rise in serum alkaline phosphatase activity. Giving 2.5 micrograms/d of 1 alpha,25(OH)2D3 did not produce these effects. Administration of 1 alpha, 25 (OH)2D3 caused an increase in intestinal calcium absorption, and a rise in serum calcium associated with a fall in serum immunoreactive parathormone (IPTH) concentrations but no sustained rise in either alkaline phosphatase, serum phosphate concentration, nor in TmPO4/GFR. Its administration caused an increase in the extent of the osteoclastic bone resorption surface but the extent of the mineralization front remained subnormal. Administration of 20 micrograms/d of 24,25(OH)2D3 caused a fall in urinary calcium excretion and in serum IPTH, and a rise in serum alkaline phosphatase, but no change in TmPO4/GFR or serum phosphate, and only a slight increase in the extent of the mineralization front. Combined treatment with 1 alpha, 25(OH)2D3 and 24,25(OH)2D3 led to a return of the mineralization front of normal even though both TmPO4/GFR and serum phosphate concentration remained low. It is concluded that 1alpha,25(OH)2D3 is not the sole biologically active metabolite of vitamin D in man. It is apparent that either 25(OH)D3 or some as yet unidentified metabolite of 25(OH)D3 stimulates the renal tubular reabsorption of calcium and phosphate, and that the subsequent rise in serum phosphate concentrations along with the direct actions of 1 alpha-25(OH)2D3, 24,25(OH)2D3, and possibly 25(OH)D3 on bone cells all participate in the restoration of normal bone formation and bone mineralization in vitamin D-deficient man.

Alkaline Phosphatase↗

Adult coeliac disease, osteomalacia, hyperparathyroidism and acromegaly. Evidence for urinary losses of hydrosoluble metabolites of vitamin D3.

Vitamin D-deficient osteomalacia with pronounced secondary hyperparathyroidism was observed in an acromegalic patient suffering from adult celiac disease. Two oral tests with tritiated vitamin D3 showed a nearly normal absorption coefficient, contrasting with a marked steatorrhea mainly due to functional and reversible pancreatic insufficiency. The urinary excretion of the radioactive label was strikingly increased and accounted for the completely flat curve of plasma radioactivity. This urinary loss of mainly water-soluble metabolite(s) of vitamin D3 represents a unique and presently unexplained feature.

Acromegaly↗

[Synthetic and biological activity of 25R and 25S diastereoisomers of dihydroxy-25,26 cholecalciferol (25,25(OH)2D3)].

The separation of 5-cholestene-3 beta, 25 (RS), 25-triol 3,26-diacetate into the diastereoisomers 25R and 25S by means of high pressure liquid chromatography (HPLC) is described. Their absolute configuration cannot be yet established. The less polar diastereoisomer is arbitrarily called 25 zeta1 and the more polar one 25 zeta2. Bromination, dehydrobromination and ultraviolet irradiation conducted to 25 zeta1, 26(OH2D3 and 25 zeta2, 26(OH)2D3 respectively. Their biological activity is described.

Animals↗