Biomedical subjects

L Miravet

Publications and source records attributed to L Miravet.

At least 37 records · Page 2Linked to original sources

PubMed1989

Cyclosporin A induces in vivo inhibition of resorption and stimulation of formation in rat bone.

We investigated a possible "in vivo" effect of cyclosporin A, an immunosuppressive agent, on normal rat bone remodeling. At an oral daily dose of 7 mg/kg for 14 days, the blood level of cyclosporin A was in the usual effective range and no change in renal function or magnesium metabolism was observed. Treated rats had decreased bone resorption: urinary hydroxyproline, plasma acid phosphatase, and the number of osteoclasts in caudal vertebrae were significantly reduced. By contrast, bone formation assessed by dynamic histomorphometry after double tetracycline labeling was increased. No modification of calciotropic hormones (vitamin D metabolites and parathyroid hormone as assessed by urinary cyclic AMP) was observed at the end of the treatment. These results suggest that in vivo cyclosporin A treatment induces bone remodeling modifications related to either a direct or a lymphokine-mediated effect on bone cells.

Acid Phosphatase↗

PubMed1989

Decreased bone formation in osteoporotic patients compared with age-matched controls.

In order to study trabecular bone remodeling in postmenopausal osteoporosis we compared bone biopsies of 44 osteoporotic women aged 50-70 to those of 23 nonosteoporotic women, matched for age, who had a bone biopsy during anesthesia for knee arthritis. Trabecular bone volume, mean wall thickness, osteoblastic surfaces, labeled surfaces, and bone formation rate were decreased in osteoporotic women compared with control women. The osteoclast number and the osteoclastic surfaces were the same in the two groups. The normal distribution of the histomorphometric static parameters in osteoporotic patients did not allow the separation of subgroups. These data indicate that decreased bone formations is a major contributing factor leading to trabecular bone loss in postmenopausal osteoporosis.

Age Factors↗

PubMed1988

Osteocalcin and bone morphometric parameters in adults without bone disease.

Serum bone Gla-protein (s-BGP or osteocalcin) and other serum biochemical parameters were measured in 19 subjects (8 women and 11 men, aged 20-82 years) without any bone disease. Each subject simultaneously underwent an iliac crest biopsy; tetracycline double-labeling was performed in 11 subjects, allowing correlations between s-BGP and bone histomorphometric parameters. s-BGP was significantly correlated with static bone parameters: trabecular bone volume (r = 0.74; P less than 0.001), osteoid surfaces (r = 0.69; P less than 0.001), osteoblastic surfaces (r = 0.68; P less than 0.002); dynamic bone formation parameters: total labeled surfaces (r = 0.72; P less than 0.01); and the bone formation rate (r = 0.69; P less than 0.01). We conclude that s-BGP is a valuable marker for evaluating bone formation in healthy adult subjects.

Adult↗

PubMed1988

[Primary hyperparathyroidism seen in rheumatology. Clinical symptoms and the relation between bone histologic signs and biological parameters].

We report the clinical and biological picture of 34 primary hyperparathyroidism (PHT) cases, diagnosed in rheumatology. It concerned 25 women and 9 men, aged 61 + 11 years. The PHT was often asymptomatic (47 p. cent of cases) at the time of diagnosis. The clinical manifestations were dominated by asthenia (50 p. cent) and renal lithiasis (47 p. cent). We found a chondrocalcinosis in 29 p. cent of patients. No patient presented any bony manifestations of cystic osteitis; 7 out of 34 patients (including 6 women between 57 and 74 years) presented vertebral compression. The mean calcemia was 117 +/- 9 mg/l. There were no hypercalcemic attack. The dosage of PTH and cyclic AMP were elevated in 29 out of 32 and 28 out of 31 patients respectively. In all patients, the level of either of these two tests was increased. The chloremia/phosphoremia ratio was also extremely predictive of HBP, since it was increased, exceeding 3.3 in 33 out of 34 patients. The 25-hydroxyvitamin D levels (25 (OH) D) were normal. The levels of 1,25 (OH) 2D were markedly spread (37 +/- 16 pg/ml) and not significantly different from the reference group. Patients with lithiasis did not present a higher level of 1,25 (OH) 2D. A bone histomorphometry carried out in 15 patients showed a bone trabecular volume similar to that of the reference with the same age. The osteoclastic resorption was increased in all cases and was not correlated with the PTH level, but was significantly correlated with the level of 1,25 (OH) 2D (r = 0.79 p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1988

The prevalence of chondrocalcinosis in the human knee joint. An autopsy survey.

The prevalence of pathological calcifications in the menisci and articular cartilage of both knees was investigated macroscopically and radiologically in 130 consecutive autopsies. The mean age of the subjects was 72 +/- 13 years. Only 8 subjects were less than 50 years old. All had been admitted to hospital and no patient had a history of joint disorders. Half of the patients were male. Calcifications were found in 27 (20.7%) cases, all over 60 years of age. There were 15.4% males and 26.1% females affected. The incidence of intraarticular calcifications in females increased from 11.1-37.5% and in males from 20-29.4% for the 60-69 year age group and the over 80-year age group, respectively. One third of affected cases had only meniscal and 2/3 had both meniscal and chondral calcifications. Isolated meniscal calcifications were found more often in 1 and mixed meniscal and chondral calcifications were found in both knees. Severe destructive articular cartilage lesions were observed significantly more often in joints with intraarticular calcifications than in joints of age matched subjects without calcifications. Joints with calcifications showed little evidence of synovial inflammation. Similarly, no specific relationship was found between the presence of crystal and amyloid deposits in the knees examined.

Aged↗

PubMed1987

Different schedules of administration of (3 amino-1-hydroxypropylidene)-1, 1 bisphosphonate induce different changes in pig bone remodeling.

Intermittent administration of antiosteoclastic agents has been proposed in order to increase trabecular bone volume (TBV). We evaluated the effect of two different intermittent schedules of administration of (3 amino-1-hydroxypropylidene)-1, 1 bisphosphonate (AHPrBP) on pig bone remodeling for a period of 60 days. AHPrBP (1.6 mumol/kg/injection) was given subcutaneously daily (group A1), or 5 consecutive days out of 21 days (group A2), or 1 out of every fourth day (group A3). Compared to control animals, group A1 significantly increased trabecular bone volume (TBV) (+62%) with a marked decrease in bone resorption assessed by interstitial bone thickness. Bone formation assessed by mean wall thickness (MWT) was also decreased due to a decrease in the number and activity of osteoblasts. There was not a delay in the coupling mechanism as assessed by the reversal surfaces. The two groups receiving intermittent schedules had markedly different results. Group A2 had very similar changes to group A1 despite receiving four time less drug. Compared to group A1 and A2, group A3 had smaller decrease in resorption and higher bone formation rate with identical MWT. These differences between group A2 and A3 were associated with similar levels of parathyroid hormone and vitamin D metabolites. Different bone concentrations induced by the two different schedules of AHPrBP may explain the greater effect on bone resorption and osteoblast recruitment in group A2 and thus a milder effect of the AHPrBP administration once every fourth day.

Animals↗

PubMed1987

Bone histological heterogeneity in postmenopausal osteoporosis: a sequential histomorphometric study.

We studied sequential bone biopsies performed at 6 to 24 month intervals from 14 untreated osteoporotic women (64 +/- 7). Subgroups were defined, respectively, by increased osteoclastic resorption surfaces and decreased osteoblastic surfaces +/- 2 S.D. Normal values were obtained from bone biopsy of 23 normal women (61 +/- 8). When patients were divided into subgroups according to the above criteria the first biopsy showed that 3 out of the 14 patients had high resorption surfaces and 6 had low osteoblastic surfaces. Eight patients spontaneously changed during the study. In 2 patients there was a change in resorption surfaces, in 3 in osteoblastic surfaces and in 3 a change in both osteoblastic and resorption surfaces was observed. Considering the first or second bone biopsy results the patient variance was higher than the control subject's variance; however the variance between the first and second bone biopsy of one patient was not different from the variance inside the group of patients. The average intraindividual variation of the parameters on sequential biopsies was of the same order as the one we previously observed on simultaneous bone biopsies of normal and hemodialyzed patients. We concluded that if osteoporosis is a heterogeneous disorder, subgroups cannot be definitively defined on the basis of cellular parameters of bone remodelling assessed on bone biopsies.

Aged↗

PubMed1987

Lack of biological activity of vitamin D3-3 beta sulfate during lactation in vitamin D-deficient rats.

Sulfoconjugated vitamin D has been claimed to have an important antirachitic activity and to be present at higher amounts than free vitamin D in maternal milk. We have previously shown that vitamin D3-3 beta sulfate (SD3) administration has little effect on calcium and bone metabolism during pregnancy in rats. In the present work, we have compared the biological activity of free vitamin D3 (D3) and SD3 during the lactation period. After delivery, D-depleted (-D) female rats were orally treated with D3 or SD3 (1,300 pmoles/every two days) during 20 days of lactation. Vitamin D status was determined before, during and at the end of the treatment for mother rats and at days 1 and 20 of life in suckling pups. Both mothers and pups were sacrificed at day 20 of lactation and subjected to hormonal and mineral determinations and to histomorphometric analysis of bone metabolism. After 12 days of SD3 treatment, mother rats showed a slight but significant elevation in plasma concentrations of calcium phosphorus and vitamin D metabolites. This effect was reversed at the end of lactation; at this time most maternal plasma parameters did not differ from those observed in -D non-treated mothers. By contrast, 20 days of D3 administration in mothers normalized plasma biochemical parameters. These results were confirmed by analysis of both static and dynamic parameters of bone formation. Maternal SD3 treatment did not improve either plasma biochemical or histological parameters of bone formation and resorption in suckling pups which remained comparable to that of D-deficient pups; by contrast, pups from D3-treated mothers normalized most biochemical plasma parameters although bone metabolism remained abnormal. In conclusion, the biological activity of SD3 on bone and mineral metabolism during lactation in rats is as low as in the nonreproductive stages.

Animals↗

PubMed1986

Assessment of vitamin D sulphate in human milk using desorption chemical ionization mass spectrometry.

Vitamin D3 sulphate (SD3) identification in human milk was obtained using Desorption Chemical Ionization (DCI). The chemical ionization reagent gas used was nitrogen, molecules were ionized when the emitter was heated. SD3 was obtained from lactarium human milk and purified by high-performance liquid chromatography (HPLC). A selected ion monitoring (SIM) measurement was carried out with typical ions, m/z 366 for SD3 and m/z 384 for parent vitamin D3, the intensity ratio (I366/I384) greater than 1 being related to the presence of the sulphoconjugated form of vitamin D3 in the sample analysed. The detection of small quantities of SD3 in human milk is possible using this technique.

Chemical Phenomena↗

PubMed1986

Bone changes due to pregnancy and lactation: influence of vitamin D status.

The effects of pregnancy and lactation on endosteal bone formation and resorption were evaluated in vitamin D-depleted (-D) and vitamin D-repleted (+D) rats. Pregnancy induced a marked stimulation of osteoclastic bone resorption and of static and dynamic parameters of bone formation and mineralization. Bone resorption increased independently of vitamin D status and did not correlate with plasma 1,25-dihydroxyvitamin D3 [1,25(OH)2D] levels, but it was associated with increased plasma immunoreactive parathyroid hormone (iPTH) concentrations. Stimulation of the endosteal bone formation rate was mainly impaired in D-depleted rats, resulting in trabecular bone loss, which, in -D mother rats, was associated with decreased bone ash and total bone calcium. Lactation further stimulated bone resorption and reduced the trabecular bone volume; ash weight and bone calcium content were also decreased independently of the vitamin D status and changes in plasma iPTH levels. In presence of vitamin D, the bone formation rate increased fourfold during lactation but was unchanged in -D lactating rats. During lactation, vitamin D-depleted rats lost twofold more calcified bone than +D rats because of impaired mineralization. Thus, the present study shows that both the endosteal bone resorption and formation are stimulated by pregnancy and lactation and that vitamin D is required for normal bone mineralization during the reproductive period.

Animals↗

PubMed1986

Relationship between the vitamin D content of maternal milk and the vitamin D status of nursing women and breast-fed infants.

This work was designed to study the effect of the vitamin D content of human milk on the vitamin D status of exclusively breast-fed infants, and the relation between milk and maternal serum concentrations of vitamin D during the first month of lactation. Serum levels of calcium (Ca), phosphorus (P), magnesium (Mg) and 25-hydroxyvitamin D (25-OH-D) were determined in a racially heterogeneous population of nursing women, between days 3 and 5 (L3), 15 and 18 (L15) and 30 and 45 (L30) post partum. The same parameters were determined in the serum of 1-month-old breast-fed infants. Maternal milk samples were obtained at L3, L15 and L30 and analysed for Ca, P, Mg, vitamin D and 25-OH-D content. Milk levels of Ca, P and Mg were found to be within the range previously described by other authors. No correlation was found between serum and milk levels of vitamin D and 25-OH-D in nursing mothers. The 25-OH-D concentration in milk was related to its vitamin D content and strongly correlated (P less than 0.001) with the 25-OH-D levels in the serum of exclusively breast-fed infants. No significant changes were observed in maternal serum levels of 1,25-dihydroxyvitamin D (1,25-(OH)2D3) measured at L3 and L30, or between maternal and infant levels of 1,25-(OH)2D3 at L30. This study emphasizes the importance of the 25-OH-D content of maternal milk, in being primarily responsible for the vitamin D concentrations found in the serum of exclusively breast-fed infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Feeding↗

PubMed1986

Calcidiol in human milk. The effect of prohormone on vitamin D status of breast fed unsupplemented infants.

Vitamin D, free or sulfoconjugated, and calcidiol (25(OH)vitamin D) levels were measured by competitive binding assay in breast milk samples of nursing mothers. Vitamin D status of their unsupplemented breast fed infants was determined. A strong correlation was established during the first month of the infant life only between calcidiol mother milk content and breast-fed infant serum. Calcidiol seems to be the vitamin D derivative mainly responsible for the maintainance of the vitamin D status of the newborn infant.

24,25-Dihydroxyvitamin D 3↗

PubMed1986

Relationship between bone GLA-protein (BGP) and calcidiol (25-hydroxycalciferol) in serum of breast-fed infants.

The aim of this investigation was to study the bone metabolism in early infancy by establishing the relationship between serum osteocalcin levels and the hormonal vitamin D status of exclusively breast-fed infants during their first month of life. Calcium, phosphorus, alkaline phosphatase, 25-hydroxycalciferol (calcidiol), 1,25-dihydroxycalciferol (calcitriol) and osteocalcin (BGP or GLA-protein) were measured in 22 healthy lactating women and their paired breast-fed infants before and after supplementation (400 IU vitamin D per day). Prior to supplementation calcidiol, calcitriol and osteocalcin remained unchanged. Following supplementation there was an increase in all the parameters with the exception of calcitriol. The administration of vitamin D to breast-fed infants should in fact have an effect on bone activity as reflected by the increase in osteocalcin levels.

25-Hydroxyvitamin D 2↗

PubMed1986

Reference intervals for vitamins B1, B2, E, D, retinol, beta-carotene, and folate in blood: usefulness of dietary selection criteria.

Reference intervals for normal concentrations in blood of vitamins B1, B2, E, D, retinol, beta-carotene, and folic acid were determined from a selected sample of people attending a Health Examination Center or being examined in occupational health services in France. This reference sample consisted of 362 men and women, ages 18 to 44 years, selected according to the main variation factors known for the vitamins studied: consumption of tobacco and alcohol, ponderal index (relating height and weight), use of drugs and oral contraceptives, and past history of surgical or medical treatment. Reference intervals were determined for each sex. Vitamin B1 (erythrocyte transketolase activity), plasma retinol, and folic acid values in whole blood are significantly higher in men than in women (p less than 0.001), but vitamin B2 (activation of erythrocyte glutathione reductase) and plasma beta-carotene values are significantly higher in women (p less than 0.001 and less than 0.01 respectively). Dietary intake of vitamins produced no significant displacement of the reference values. For each vitamin we discuss the other major sources of variation factors and the usual values reported in the literature.

Adolescent↗

PubMed1985

Osteoclast abnormalities in idiopathic osteopetrosis. Reference to the ultrastructural histochemistry study.

In order to investigate skeletal abnormalities in a case of idiopathic osteopetrosis, a bone biopsy was taken from the anterior iliac crest and prepared for ultrastructural and histochemical study. There was a drastic reduction in osteoclastic bone resorption. The ruffle border and sealing zone, which are the osteoclast cell surface markers of bone resorption, were absent. The cells were highly vacuolated, and the vacuoles contained large amounts of a residual organic material which reacted strongly with acid phosphatase. Acid phosphatase activity was never found outside the cell, and in particular, not at the bone-cell interface. This suggests that the defect in bone resorption is caused by cell membrane abnormalities and the lack of ruffle border formation, rather than the inability of the lysosomal enzymes to digest the bone matrix.

Acid Phosphatase↗

PubMed1985

Histomorphometric evidence of deleterious effect of aluminum on osteoblasts.

Bone histomorphometry was performed in 26 hemodialyzed patients to study the relation between the dynamic parameters of bone formation and aluminum deposition. Patients were divided into two groups according to whether bone formation rate at tissue level (Svft) was above or below normal: 0.089 mu 3/mu 2 per day. The 12 patients who constituted group II, defined by a Svft less than 0.089 mu 3/mu 2 per day, had markedly decreased extent of double-labeled surfaces (m = 1.3 +/- 6.5%), and these were absent in 8 of 12 patients. Osteomalacia, defined by decreased formation with increased mean osteoid thickness (greater than 15 micron), was present in only 3 of 12 patients in group II. The 14 patients who constituted group I, defined by a Svft greater than 0.089 mu 3/mu 2 per day, had both increased total labeled surfaces and mineralization rate. Osteomalacia was present in none of the group I patients. In trabecular bone, group II patients had increased stainable aluminum deposition, compared to group I patients, whether estimated as total stainable aluminum (2.16 +/- 1.34 vs 0.17 +/- 0.28 mm/mm2) or stainable percent of trabecular surfaces (42 +/- 19 vs 4 +/- 5%). This last parameter was inversely related to osteoblastic surfaces (r = -0.49, n = 26, P less than 0.01) and total labeled surfaces (r = -0.72, n = 26, P less than 0.01). Therefore, massive aluminum deposition was not invariably associated with impaired mineralization but with decreased formation due to decreased extent of active formation surfaces. In the group I patients, moderate aluminum deposition was not associated with the mineralization arrest observed in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1985

Increased bone aluminum deposition after subtotal parathyroidectomy in dialyzed patients.

Ten dialyzed patients underwent a systematic bone biopsy before and 19 +/- 9 months after subtotal parathyroidectomy (PTX). At the end of the follow-up period all the patients, except two, who complained of proximal myalgia, were asymptomatic. Compared to the bone biopsy specimen obtained prior surgery, decreased bone formation without mineralization impairment was observed after PTX. Despite an average decrease in aluminum gels intake after PTX, an increase in stained aluminum was observed (0.69 +/- 0.79 versus 1.20 +/- 0.95 mm/mm2, P less than 0.050). Aluminum accumulation depended on the pre-PTX bone aluminum load: pre- and post-PTX bone aluminum loads were correlated (r = 0.78, P less than 0.01). Bone aluminum accumulation was not related to the amount of aluminum gel intake after PTX; however, only two patients free of both bone aluminum deposit prior to PTX and aluminum gel intake after PTX had no stainable aluminum on the second bone biopsy after PTX. The only patient who had no decrease in bone formation after PTX had no increase in bone aluminum. Assuming that the patients had no aluminum deposit prior to dialysis, we measured the rate of bone aluminum accumulation. It rose from 0.11 +/- 0.09 mm/mm2/year prior to PTX to 0.40 +/- 0.25 mm/mm2/year after PTX (P less than 0.05) in the six patients who were maintained on phosphate binders and who had a decrease in bone formation after PTX. These six patients had unchanged aluminum gel intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1985

Effect of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 maternal loads on maternal and fetal vitamin D metabolite levels in the rat.

Two groups of female rats were used to investigate vitamin D metabolism in the pregnant animals and in their fetuses. In the first group, 3 micrograms of 25-hydroxyvitamin D3 (25-OH-D3) per kg of body weight were injected into intact or nephrectomized (NX) pregnant rats 3 h before sacrifice on day 21 of pregnancy; in the second group, 2 and 6 ng, respectively, of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) per day were infused continuously into pregnant rats between days 17 and 21 of pregnancy. The findings in the fetuses were obtained by quantitative analysis of extracts (Extrelut) of total fetal body lipids; the extracts were purified on Sep Pak and vitamin D sterols were further separated by high-pressure liquid chromatography. Three hours after the dams were injected with 25-OH-D3, the maternal plasma concentration (mean +/- SD) of 1,25(OH)2D3 was 221 +/- 84 pg/ml. In NX pregnant rats, the 1,25(OH)2D3 levels were still elevated: 95.6 +/- 49.0 pg/ml vs 45 +/- 22 pg/ml in control rats. In fetuses from intact or NX dams, the levels of 25-OH-D3 and 1,25(OH)2D3 were not different from the results obtained in the control fetuses but 24,25(OH)2D3 concentrations were increased (6.7 +/- 1.2 ng vs 2.2 +/- 0.7 ng/g body weight). After maternal infusion of 2 or 6 ng/day of 1,25(OH)2D3 (n = 8), plasma concentrations (mean +/- SD) of the metabolite were 64 +/- 31 and 517 +/- 356 pg/ml, respectively, the second being significantly higher than that of the control rats; 25-OH-D3 and 24,25(OH)2D3 levels did not change. 1,25(OH)2D3 contents (mean +/- SD) in fetuses from the treated dams were not different from those of control fetuses (10 +/- 2 pg/g body weight). Our results suggest that pregnant rats and their fetuses were protected against an excessive increase of 1,25(OH)2D3 concentrations in the maternal plasma; although there was some individual hypercalcemia, no significant increase in mean calcemia was detected in the dams, and 1,25(OH)2D3 either did not cross the placental barrier or was rapidly metabolized because we did not find any changes in the fetal content. As in intact or NX pregnant rats, 25-OH-D3 was metabolized into 1,25(OH)2D3, the increase of 24,25(OH)2D3 in the fetuses might be associated with a protective mechanism.

Acid Phosphatase↗