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Biomedical subjects

S Gaspar

Publications and source records attributed to S Gaspar.

At least 19 recordsLinked to original sources

Prevention of osteoporosis with nasal salmon calcitonin: effect of anti-salmon calcitonin antibody formation.

The amino acid sequence of salmon calcitonin (SCT) differs considerably from that of the human hormone and specific antibodies (Ab) develop in a significant proportion of patients after parenteral or nasal administration of SCT. Controversy remains regarding the functional importance of these Ab. We report on the development of specific anti-SCT Ab in a population of postmenopausal women receiving nasal SCT for prevention of postmenopausal bone loss, and compare the effects of nasal SCT in women with or without Ab. Thirty-nine per cent of women developed Ab after 6 months of treatment with SCT, 52% after 12 months, and 61% after 18 and 24 months. After 24 months the AB titre was 3.47-17.7 x 10(-9) M/l (mean +/- SD: 13.3 +/- 3.1 x 10(-9) M/l). No significant differences appeared between the changes in lumbar bone mineral density (BMD) measured in the whole population (n = 44) (mean +/- SD: +1.06 +/- 3.9%), the patients without Ab (n = 17) (+0.05 +/- 3.7%) or in those with Ab (n = 27) (+1.7 +/- 4.6%). During the same period, a control population randomly assigned to a 500 mg/day calcium intake showed a significant loss of lumbar BMD (-4.57 +/- 4.9%) (p < 0.01). In conclusion, in healthy postmenopausal women nasal SCT seems to maintain the same preventive effect against bone loss whether or not Ab are present.

Administration, Intranasal

Endogenous production of specific antibodies does not decrease hypocalcemic response to calcitonin in young rabbits.

In order to evaluate the potential inhibition of the acute anti-osteoclastic activity of salmon calcitonin (SCT) by specific antibodies (Ab), we compared the SCT-induced hypocalcemic effect in young male rabbits with significant titers of high affinity Ab and in matched animals without Ab. Immunization of rabbits was performed by repetitive s.c. injections of SCT and Freund adjuvant. Ab were present in four-fifths of SCT-treated rabbits (Ab+). Their titer varied from 0.8 x 10(-9) to 30 x 10(-9) M/liter and their constant of affinity from 0.97 x 10(9) to 4.2 x 10(9) L/M. Intravenous injection of 1 IU/kg SCT to Ab+ rabbits induced a significant decrease (P less than 0.01) of ionized serum calcium (Ca2+) after 30 minutes (mean +/- SD: -9 +/- 0.6%) and until the 240th minute of the test (-16.7 +/- 4.7%), with a maximum after 120 minutes (-22.6 +/- 2%). This was not significantly different from the hypocalcemic effect measured after the same procedure performed in matched animals without Ab (Ab-): significant decrease in Ca2+ (P less than 0.01) after 30 minutes (-8.2 +/- 2.2%), maximal after 150 minutes (-23.2 +/- 4.9%), and lasting until 210 minutes (-14.5 +/- 3.7%). We conclude that, in the particular model of the male young rabbit, specific anti-SCT Ab do not block or reduce the acute anti-osteoclastic activity of SCT.

Animals

Study of the formation of prechondral blastemas in the autopodium of normal and polydactyl rats.

The nuclear volume fractions in chosen mesenchymal and prechondral zones were examined during formation of the prechondral rays in the autopodium of 14- and 15-day rat embryos. A morphometric analysis showed that formation of the prechondral blastemas was accompanied by a significant increase in the nuclear volume fraction in relation to the adjacent distal mesenchyme in both normodactyl and polydactyl embryos. The mean nuclear volume fraction in the prechondral blastema (the third metatarsal ray) is somewhat larger in normodactyl embryos, but the differences (in progressive means) are not statistically significant. The nuclear volume fractions at chosen sites in the mesenchymal zones at 14 and 15 days do not differ significantly in either normodactyl or polydactyl embryos. There are, however, significant differences between the nuclear volume fractions of the mesenchymal cells at the chosen sites in normodactyl and polydactyl embryos at both 14 and 15 days. The degree of enlargement of the nuclear volume fraction in the prechondral (chondrogenic) ray in relation to the mesenchyme is relatively greater in polydactyl embryos than in normodactyl embryos.

Animals

Influence of the nature of calcium salts on serum calcium, phosphorus, calcitonin, growth hormone, and somatomedin C.

Twenty healthy males were randomly divided into three groups. Each subject received either 405 mg elemental calcium (Ca) as a salt linked to an amino acid precursor, 405 mg CaC12 or 1000 mg Ca as Ca gluconolactate and carbonate. In all three cases, Ca intake led to an increase of serum Ca and TCT production and a decrease of PTH liberation. However, when Ca is linked to the amino acid precursor, an elective stimulation of growth hormone (GH) and somatomedin C (SmC) occurs. Due to the nature of its amino acid precursor, this salt seems to stimulate GH and SmC liberation through hypophysis. This could be a major pathway in decoupling of the sequence resorption-formation and therapy of metabolic bone diseases.

Adult

Measurement of proteoglycans, elastase, collagenase and protein in synovial fluid in inflammatory and degenerative arthropathies.

The number of leucocytes and the concentrations of protein, proteoglycans (PG), elastase a1 proteinase inhibitor complexes (E-alpha 1 Pi) and collagenolytic activity were measured in the synovial fluid (SF) of 15 patients with rheumatoid arthritis (RA) and 18 with osteoarthritis (OA). The mean levels of protein, E-alpha 1 Pi and collagenase and the number of leucocytes were higher in RA than in OA SF. However, the mean level of PG was higher of OA SF than in RA. In the latter, they were principally in the form of monomers and fragments while in the former they were in the form of aggregates and monomers. There was a direct relationship between the concentration of E-alpha 1 Pi and either the number of white cells or the concentration of synovial proteins, suggesting that the measurement of E-alpha 1 Pi complexes is a biochemical index of the local inflammatory reaction. There was an inverse correlation between the concentrations of PG and E-alpha 1 Pi which may reflect the effect of degradation in PG of elastase and other enzymes released at the same time. Finally, there was a direct relationship between the concentration of E-alpha 1Pi and collagenase which may be the reflection of a simultaneous release of various enzymes from leucocytes and macrophages.

Arthritis, Rheumatoid

[In vitro incorporation of radioactive sulfur into proteoglycans of cartilage. Effects of various nonsteroidal anti-inflammatory agents].

Radioactive sulphur (35SO4) is incorporated in the proteoglycans of chicken embryonic cartilage. In fact, the molecular weight of the macromolecules which bind the sulphur corresponds to monomeric proteoglycans and proteoglycan-hyaluronic acid complexes. This incorporation does not take place when the cartilage has been previously killed. The capture of 35S is stimulated by human serum, in a dose-dependent way. At doses less then, equal to and greater than the maximal plasma concentrations observed following a single oral dose (600 mg), acetyl salicylic acid and sodium salicylate inhibit the incorporation of radioactive sulphur in the cartilage. Under the same conditions, tiaprofenic acid and oxametacine have no effect on this metabolic parameter.

Animals

Responses to salmon calcitonin in chronic renal failure: relation to histological and biochemical indices of bone turnover.

Twenty-one patients with chronic renal failure and bone disease or hypercalcaemia were studied before and following single (twenty patients) or repeated (fourteen patients) intravenous injection of synthetic salmon calcitonin. Significant correlations were noted before treatment between bone surfaces occupied by osteoblasts or osteoclasts and plasma levels of immunoreactive parathyroid hormone, alkaline phosphatase and hydroxyproline. Following a single injection of 2--200 i.u. salmon calcitonin, plasma levels of calcium and phosphate fell for 6--8 h, but rose subsequently to pre-injection levels at 24 h. The magnitude and duration of the hypocalcaemic response was not clearly dose-dependent, but correlated with measured indices of bone cell activity. Repeated administration of calcitonin (10--200 i.u. thrice weekly for up to 2 months) lowered plasma calcium in the majority of patients and restored plasma calcium to normal in four previously hypercalcaemic patients. Mean levels of alkaline phosphatase increased but no significant changes in plasma phosphate, immunoreactive parathyroid hormone and calcitonin, or hydroxyproline occurred. Calcium absorption (six studies) did not change during treatment. We conclude that synthetic salmon calcitonin is an effective short-term inhibitor of bone resorption in patients with chronic renal failure. Its use as a possible treatment for hypercalcaemia and hyperparathyroid bone disease in chronic renal failure is discussed.

Adult

Lack of clinical and physiological relationship between gastrin and calcitonin in man.

The clinical and physiological relevance of the relationship between gastrin and calcitonin has been investigated in normal subjects and in patients suffering from gastritis or duodenal ulcer. Basal plasma levels of calcitonin are increased in these patients but there is no significant relationship between calcitonin and gastrin levels. Acute pentagastrin injection in normal male subjects increased significantly (P less than 0.05) plasma calcitonin levels whereas lower doses of pentagastrin which are known to stimulate gastric secretion are without effect on calcitonin levels. Moreover, stimulation of gastrin secretion by a protein test meal and by intragastric administration of a calcium chloride solution is not followed by any significant increase of plasma calcitonin levels. These results suggest that the stimulation of calcitonin secretion by gastrin and its synthetic analogue pentagastrin is a pharmacological rather than a physiological phenomenon.

Adult

Comparison of acute effects of 1.25- and 24.25-dihydroxy-vitamin D3 in normal subjects.

Effects of small iv doses of 1.25-dihydroxy- and 24.25-dihydroxy-vitamin D3 (a microgram) were studied in 10 normal subjects. Injection of 1.25 (OH)2D3 was associated with small but significant increases in plasma calcium and phosphate but plasma levels of immunoreactive parathyroid hormone (iPTH) and calcitonin (iCT) did not change. The administration of 24.25 (OH)2D3 was associated with comparable decreases in plasma calcium and a small and transient decrease in plasma iPTH. Plasma levels of iCT did not change. 24.25 (OH)2D3 also significantly increased glomerular filtration rate and decreased the urinary excretion of noradrenaline, in contrast to 1.25 (OH)2D3 which had no effect on these variables. The rapid infusion of calcium significantly decreased levels of iPTH. We conclude that small doses of 1.25 (OH)2D3 and 24.25 (OH)2D3 have little, if any, direct effect on the secretion of PTH and CT in man.

24,25-Dihydroxyvitamin D 3

[Radioimmunoassay for type II amino-terminal procollagen peptide. Technical note].

We have studied the immunoreactivity of human sera and synovial fluids in a radioimmunoassay which utilizes an anti-bovine procollagen type III antiserum and the bovine type III procollagen peptide as standard and tracer. We have noticed a complete cross reaction between bovine col 1-3 and human synovial fluid, which thus contains substance (s) having the same antigenic determinant (s) as col 1-3. On the contrary, we have demonstrated non parallelism between col 1-3 and human serum, whether the serum was obtained from normal subjects or patients suffering from various diseases. These results suggest that immunoreactive substances related to col 1-3 and detected in sera are at least partially different from those detected in synovial fluids.

Animals

[Demonstration of multiple forms of immunoreactive calcitonin (CTi) in human serum by isotachophoresis. Preliminary results].

Heterogeneity of immunoreactive calcitonin (iCT) in the serum has been studied by preparative isotachophoresis. Under the described technical conditions, it is possible to distinguish several molecular species of iCT characterized by a faster mobility than synthetic CT. Preliminary results suggest that immunoreactive CT profile is not similar in various hypercalcitonemic diseases.

Calcitonin

Ethanol induced secretion of calcitonin in chronic renal disease.

Whisky (25-50 ml) increased plasma levels of immunoreactive calcitonin (iCT) in seventeen of nineteen patients with chronic renal failure. The effect was greater in patients with high levels of iCT than in those with normal levels. Changes in plasma iCT were not related to changes in calcium, phosphate or immunoreactive gastrin, but were inhibited by the prior administration of propranolol.

Calcitonin

[The effects of 1 alphahydroxycholecalciferol in patients with renal osteodystrophy, Paget's disease of bone and in normal subjects (author's transl)].

The administration of 1 alpha hydroxycholecalciferol (1 alpha OHD3) (2 microgr. per day) increase the plasma immunoreactive calcitonin (i CT) concentration in normal subjects after six days. This effect is also observed in patients suffering from Paget's disease of bone, suggesting that the mechanism responsable for the secretion of CT following the administration of 1 alpha is not disturbed in that disease. By contrast, the absence of increase in plasma iCT in the patients suffering from chronic renal failure suggests an impaired secretion of CT in that disorder.

Calcitonin