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Biomedical subjects

M Azria

Publications and source records attributed to M Azria.

At least 19 recordsLinked to original sources
PubMed1996

The effect of intranasal salmon calcitonin on postmenopausal bone turnover as assessed by biochemical markers: evidence of maximal effect after 8 weeks of continuous treatment.

Although treatment with intranasal salmon calcitonin (sCT) has been shown to effectively inhibit postmenopausal bone loss, there is still controversy over both timing and the duration of its application. In an open prospective study, we therefore assessed the effect of shortterm intranasal sCT on postmenopausal bone turnover, employing biochemical markers of bone metabolism. Ten early postmenopausal, previously untreated women (1-5 years after menopause) with biochemical evidence of increased bone resorption and a low bone mineral density at baseline were treated with intranasal sCT (100 IU B.I.D.) for a period of 3 months. Oral calcium (500 mg/day) was administered simultaneously, and during a further 3 month follow-up interval. Treatment with sCT resulted in a pronounced suppression of bone resorption markers with a maximum effect reached after 8 weeks of therapy: as compared to the respective baseline values, mean levels decreased by -26.2% +/- 3.4% (P < 0.001) for pyridinoline, -32.7% +/- 3.5% (P < 0.001) for deoxypyridinoline, -32.7% +/- 3.3% (P < 0.001) for hydroxyproline, and -24.1% +/- 8.2% (P < 0.001) for the amino-terminal telopeptide. In contrast, changes in bone formation markers of osteocalcin (-14.4% +/- 4.8%, P < 0.05) and C-terminal procollagen type I propetide (-7.9% +/- 3.9%, ns) were much less pronounced. Unexpectedly, after week 8 of the study all resorption markers showed a plateau and a trend to increase, although intranasal sCT was continued for a total of 12 weeks. This effect could not be attributed to the formation of anti-sCT antibodies. After cessation of treatment, both bone formation and resorption markers rapidly returned to baseline levels. Bone mineral density of both spine and hip showed no significant change during the observation period. Our results demonstrate that in postmenopausal women with a high bone turnover, intranasal treatment with 200 IU of sCT effectively reduces bone turnover and maintains bone mass, the maximum effect being reached after 8 weeks of treatment.

Administration, Intranasal↗
PubMed1995

Osteoporosis.

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Aerosols↗
PubMed1994

Comparison of the acute biological action of injectable salmon calcitonin and an injectable and oral calcitonin analogue.

In most countries, calcitonin is available in the form of injections, and less frequently as an intranasal spray. An oral route of administration should improve compliance. In a preliminary feasibility study, we have compared the acute biological action of injectable salmon calcitonin (50 IU), with the injectable calcitonin analogue ASC 710 (0.2 mg) and oral ASC 710 (20 mg) in 6 patients suffering from active Paget's disease of bone. The intensity and duration of the biological response were not significantly different in the 3 modes of therapy. In conclusion, the oral calcitonin analogue ASC 710 possesses an antiresorbing activity in Paget's disease comparable to that of an injection of salmon calcitonin which demonstrates that it can cross the intestinal barrier.

Administration, Intranasal↗
PubMed1993

Lack of effect of ipriflavone on osteoclast motility and bone resorption in in vitro and ex vivo studies.

Using in vitro and ex vivo experimental procedures specifically designed to visualize pharmacological effects on parameters of bone resorption, studies were performed to elucidate whether ipriflavone's reported effect in osteoporosis is due to an effect on the motility and resorptive activity of osteoclasts, as has been shown to be the case with salmon calcitonin. Concentrations of ipriflavone used were higher by a factor of > 100 than peak blood levels measured in patients given standard therapeutic doses. Despite this, neither quantitative nor qualitative changes were observed in the motility of isolated rat osteoclasts or in their resorptive activity when incubated with bone slices. The conclusion is that ipriflavone does not possess antiosteoclastic and antiresorptive activity of the type documented for salmon calcitonin in the models employed and that further investigation of its mode of action is therefore necessary.

Animals↗
PubMed1992

N-terminal truncation of salmon calcitonin leads to calcitonin antagonists. Structure activity relationship of N-terminally truncated salmon calcitonin fragments in vitro and in vivo.

Structural requirements for binding to the bone calcitonin (CT) receptor and for CT bioactivity both in vitro and in vivo were assessed for a series of N-terminally truncated, N alpha-acetylated, fragments of salmon calcitonin (sCT). Sequential deletion of amino acid residues from the amino-terminus of [Ala7]sCT-(2-32) peptide amide first led to partial agonists and, upon deletion of residues 1 to 7, to a high affinity antagonist, N alpha-acetyl-sCT-(8-32)-NH2. The presence of two separate domains within the sCT sequence is proposed: (I) a binding domain comprising residues 9-32 and (II) an activation domain requiring residues 3 to 6. N alpha-acetyl-sCT-(8-32)-NH2, in several bioassays including plasminogen activator release from LLC-PK1 cells (pA2 = 7.31), cAMP production in UMR-106-06 cells (pA2 = 7.81) and in the fetal rat long bone resorption assay showed potent antagonistic properties.

Acetylation↗
PubMed1992

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↗
PubMed1987

The effect of rectal and nasal administration of salmon calcitonin in normal subjects.

In order to ascertain the blood levels and the biologic responses obtained after administration of two noninjectable forms of salmon calcitonin (SCT) (i.e., a nasal spray and a suppository), two doses of 200 IU each were administered at 3 hour intervals nasally to 8 normal subjects, and rectally to 9 normal subjects. Five untreated subjects served as controls. All were given a standardized diet for 2 days before the test. Plasma salmon-calcitonin, ionized calcium, phosphate, sodium, proteins, creatinine, and alkaline phosphatase were measured repeatedly after the administration of the drug. Modifications in fractionated urinary calcium, phosphate, sodium, and creatinine excretions (and hydroxyproline for the 8 subjects treated by the nasal spray) were compared with the values measured on the previous day. Plasma concentrations of SCT were found to increase sharply with both routes of administration, the peaks being high and short after rectal administration, low but more sustained after nasal application. Despite these differences, almost similar biologic effects could be demonstrated: transient hypocalcemia, increased calciuria, phosphaturia, and natriuria. Urinary hydroxyproline excretion decreased. Plasma sodium did not increase, whereas it did in the controls. In conclusion, nasal sprays and suppositories of SCT appear to exert the known biologic effects of SCT, and might be favored for long-term treatment in diseases representing indications for calcitonin therapy.

Administration, Intranasal↗
PubMed1987

Effectiveness of salmon calcitonin administered as suppositories in tumor-induced hypercalcemia.

Although calcitonin is a natural, nontoxic, and rapid inhibitor of bone resorption, its use in the treatment of hypercalcemia is limited because of its transient efficacy and the need for repeated parenteral administration. In normal subjects, suppositories of calcitonin have been shown to be biologically active. Peak plasma concentrations of salmon calcitonin after rectal administration in six normal subjects were similar to those measured after parenteral administration. To evaluate the efficacy of calcitonin suppositories in disease states, 10 patients with moderate hypercalcemia due to malignancy were treated with salmon calcitonin, administered as suppositories containing 300 MRC units, three times a day for seven days. The mean plasma calcium level decreased significantly from 2.96 +/- 0.09 mmol/liter to 2.57 +/- 0.09 after one week (p less than 0.005) and rose again after discontinuation of treatment to 2.86 +/- 0.09 mmol/liter one week later. Urinary calcium and hydroxyproline values decreased during treatment and rose after discontinuation of treatment. The plasma calcium level decreased rapidly in six patients, becoming normal in five; three patients showed only a partial response, and one patient had no response at all. No side effects were observed, and clinical improvement was noted in nine of the 10 patients. Little or no response was observed in patients with extremely high urinary calcium or, to a lesser extent, high hydroxyproline excretion. There was a significant negative correlation between the maximal decrease in plasma calcium concentration and initial urinary calcium excretion (r -0.78, p less than 0.01). Thus, salmon calcitonin administered by the rectal route appears to be an easy, safe, and effective treatment of moderate hypercalcemia without apparent side effects.

Administration, Rectal↗
PubMed1985

Decreased responsiveness to chronic salmon calcitonin treatment in rat kidney and calvaria studied using quantitative enzyme cytochemistry.

Growing rats were treated with daily im doses of salmon calcitonin (sCT) (2, 15 and 100 IU/kg) for various times (1, 4 and 24 weeks). The effects on intracellular enzyme activities in bone and kidney were monitored using quantitative cytochemical methods previously developed for the identification of specific target tissue responses to calcitonins. The basal alkaline phosphatase activities in both kidney and bone were decreased by long-term treatment at all time periods and doses tested. No change was noted in basal Ca ATPase activities in kidney after treatment. The capacity of target tissues in chronically treated and control rats to respond to an acute iv dose of sCT was also compared. Acute provocation tests in treated and control rats showed that the renal alkaline phosphatase response was decreased in the rats receiving long-term treatment. Moreover, the direction of response was reversed in chronically treated rats when bone alkaline phosphatase and renal Ca-dependent ATPase activity was measured after acute provocation with sCT, i.e. bone alkaline phosphatase was stimulated instead of being inhibited and renal Ca ATPase was inhibited instead of being stimulated. The application of quantitative cytochemical techniques has demonstrated intracellular changes in enzyme activities in both kidney and bone. The impaired sCT responsiveness can be detected at shorter times of treatment (1 week) and lower doses (2 IU/kg) than has previously been possible by measurement of indices of mineral metabolism in plasma or urine.

Alkaline Phosphatase↗
PubMed1984

The myotropic and plasma-calcium modulating effects of calcitonin gene-related peptide (CGRP).

Human and rat calcitonin gene-related peptides cause a dose-related contraction of guinea pig ileum, which is antagonised by an anti-histamine, mepyramine, and an anticholinergic compound, hyoscine. Both peptides also cause a positive inotropic and a positive chronotropic effect in the rat isolated auricle and these responses are antagonised by propranolol, a B adrenoceptor blocker. Further, the peptides lower plasma calcium levels in both rats and rabbits in a dose-related manner resembling calcitonin; in the rabbit, but not in the rat, the initial calcium lowering effect is succeeded by hypercalcaemia at higher doses, while in the chick, only the parathyroid hormone-like calcium-raising effect is seen.

Animals↗
PubMed1983

Quantitative cytochemical responses to exogenously administered calcitonins in rat kidney and bone cells.

Time- and dose-dependent changes in intracellular enzyme activities in kidney and bone from rats injected with calcitonin have been assessed by quantitative cytochemistry. The doses of salmon calcitonin given were similar to those suggested in the Pharmacopoeial rat hypocalcaemia bioassay (1-50 mIU/50 g body weight). The highest doses produced 30% inhibition of alkaline phosphatase activity, maximal within 20 min after injection, in cells of renal proximal tubules and a stimulation of calcium-dependent adenosine triphosphatase activity in kidney cortical and outer medullary cells. Alkaline phosphatase activity in the periosteal bone cells was markedly inhibited at the lowest doses. When doses of human and porcine calcitonins were given which would be equipotent with that of salmon calcitonin in the rat hypocalcaemia bioassay, the effect of the non-mammalian peptide on renal alkaline phosphatase activity was relatively greater than that of the mammalian peptides. Oxidized human calcitonin did not inhibit renal alkaline phosphatase activity even when an amount equivalent to 10 times the highest dose of the unmodified peptide was injected.

Alkaline Phosphatase↗
PubMed1982

Flow measurement of blood radioactivity in animals.

In order to permit flow measurement of blood radioactivity in an animal after establishing extracorporeal circulation, counting cells were constructed of various plastic scintillator materials. The cell was placed in a liquid scintillation spectrometer replacing the sample vial. Stable and reproducible counting rates were obtained only with cells made of blue Altustipe plastic. The counting efficiency was 1.8%. Using this detection system, continuous records were produced of blood radioactivity in miniature pigs after administration of 14C-urethane and [14C]methyl-piperazinyl pyrazino benzoxazepine maleate.

Animals↗