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Biomedical subjects

M Brazier

Publications and source records attributed to M Brazier.

At least 55 records · Page 3Linked to original sources
PubMed1996

Different responses of free and peptide-bound cross-links to vitamin D and calcium supplementation in elderly women with vitamin D insufficiency.

Recent findings have shown that bisphosphonates had different effects on the urinary excretion of free and peptide-bound cross-links. Because of this discrepancy, we investigated the effects of another antiresorptive therapy, i.e. vitamin D (vitD) and calcium (Ca) supplementation (800 IU vit D3 and 1 g elemental calcium daily for 6 months) in elderly women (n = 21, age: 83.5 +/- 1.5 yr) with vitD insufficiency and secondary hyperparathyroidism (mean level 25 hydroxy vitamin D = 3.17 +/- 1.2 ng/mL, mean level of intact parathormone = 45.3 +/- 22.7 pg/mL) on the urinary excretion of free and peptide-bound cross-links. A group of free-living, healthy elderly women (n = 25, age: 76.6 +/- 3.1 yr) with a normal vitD status (mean level of 25 OH D = 23.4 +/- 8.9 ng/mL, intact parathormone = 30.2 +/- 11.2 pg/mL) was simultaneously studied. Bone resorption was assessed by total (T), free (F), peptidyl (P) hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) measured with high performance liquid chromatography, by F-LP determined with enzyme linked immunosorbent assay (iF-LP) and by the N- and C-terminal telopeptides of type I collagen (NTX and Cross-laps) before and after (3 and 6 months) therapy. Comparison of the two groups of elderly women at baseline showed that the urinary excretion of pyridinoline cross-links (T, F, and peptide-bound forms) and of telopeptide fragment of type I collagen were all increased in patients with a low vitD status. Highly significant differences were seen principally for T-HP, F-HP, and F-LP (P < 0.001). Correlation studies between each marker showed that the values of pyridinoline cross-links (T and peptide-bound forms) and of the telopeptide fragments of type I collagen correlated well, but the correlation was slightly less pronounced between free pyridinolines and the other markers. After treatment, the response to therapy was greatest for peptide-bound cross-links assessed by high performance liquid chromatography and for telopeptide fragments of type I collagen (percent change at 6 months: -21% for P-HP P < 0.05, -26% for P-LP P < 0.05, -31% for NTX P < 0.01, and -51% for CLaps P < 0.001). In contrast, free pyridinolines excretion (F-HP and F-LP) assessed by high performance liquid chromatography as well as by immunoassay remained unchanged at 3 and 6 months. Because marked and significant changes were seen with peptide-bound cross-links only and not with free forms, we conclude that vitD and Ca therapy has the same effects as bisphosphonates on the urinary excretion of free and peptide-bound cross-links. So far, no rational mechanism can be given to explain this discrepancy, and further studies are needed before routine application of these bone collagen degradation products as bone resorption markers.

Aged↗
PubMed1996

[Urinary excretion of free and total deoxypyridinoline during secondary hyperparathyroidism in the elderly. Comparison of chromatographic (HPLC) and immunoenzymatic (Pyrilinks-D) methods].

The measurement of urinary deoxypyridinoline (DPD) constitutes a specific and sensitive marker of bone resorption. Total and free forms of DPD are determined by chromatographic method (HPLC) after or without hydrolysis of urine, respectively. Pyrilinks-D, a new immunoassay, allows to assess directly the free forms and needs an appropriate hydrolysis step for measuring the total form. We have compared the values of free (F), total (T) and conjugated (NF) forms of DPD determined by HPLC and Pyrilinks-D, in elderly women (n = 21, mean age: 83.5 +/- 1.5 years) with vitamin D insufficiency (25 OH D < 6 ng/mL) and Ca insufficiency responsible for a secondary hyperparathyroidism (iPTH = 45.3 +/- 22.7 pg/mL) and in healthy elderly women (n = 25, mean age: 76.6 +/- 3.1 years) with a normal vit D status (25 OH D > 10 ng/mL) as control group. We have also measured DPD during the course of vit D and Ca supplementation. At baseline, the HPLC and Pyrilinks-D values of DPD/Cr are highly correlated (DPD-T: r = 0.92, p < 0.001 and DPD-F: r = 0.76, p < 0.001), DPD-F and -NF values are correlated with those of DPD-T, while DPD-F and -NF are not correlated between themselves. In elderly with vit D insufficiency, the values obtained with Pyrilinks-D as compared to control subjects, show a significant increase of urinary excretion of DPD-F (8.5 +/- 3.1 vs 5.7 +/- 1.9 nmol/mmol, Cr, p < 0.0001), DPD-T (16.8 +/- 10.2 vs 9.9 +/- 3.5 nmol/mmol, Cr; p < 0.001) and DPD-NF (8.3 +/- 9.0 vs 4.5 +/- 3.3 nmol/mmol, Cr, p < 0.05). The administration of 800 IU of vit D and 1 g of elemental Ca during a course of 6 months normalize the iPTH values (24.4 +/- 11.8 and 30.9 +/- 14.6 pg/mL at 3 and 6 months). Simultaneously, the urinary excretion at 3 and 6 months of DPD-T (12.9 +/- 6.0 and 13.6 +/- 6.5 nmol/mmol, Cr) and of DPD-NF (4.5 +/- 3.3 and 5.5 +/- 4.8 nmol/mmol Cr) assessed by Pyrilinks-D as well as by HPLC decreased significantly, while no change was seen with DPD-F assessed by both methods. The decreases expressed as percent of baseline values were about 20% for DPD-T and more than 30% for DPD-NF, while DPD-F levels remain unchanged. We conclude that the Pyrilinks-D immunoassay presents reliable characteristics and allows to assess either free or total forms of DPD, like the HPLC technique. It constitutes an excellent reflection of bone resorption in elderly with vit D insufficiency. However its application to monitor therapy like vit D and Ca supplementation, needs a hydrolysis step to determine DPD-T which appears in this study more sensitive to the treatment than DPD-F.

Aged↗
PubMed1995

A simple and automated HPLC method for determination of total hydroxyproline in urine. Comparison with excretion of pyridinolines.

An HPLC method for measuring total hydroxyproline in human urine was validated. Hydroxyproline derivatization was achieved with 9-fluorenylmethyl chloroformate after blocking primary amino acids with orthophthaldialdehyde. The derivatives (hydroxyproline and internal standard) were separated by reversed phase high-performance liquid chromatography and detected by absorbance at 254 nm. Duplicate measurements of hydroxyproline have a coefficient of variation of 3.9% and the recovery in spiked urine samples is between 99.5 and 100.8%. We have compared the HPLC procedure with a commercial colorimetric assay. Analytical criteria of these methods are identical. Regression analysis, involving 50 samples, shows an excellent correlation between hydroxyproline chromatographic (y) and colorimetric (x) procedures: y = 0.989x + 2.99 (r = 0.976). Hydroxyproline excretion was determined in urine samples from 76 women more than 5 years post-menopause. The mean hydroxyproline/creatinine ratio in this group was 19.3 +/- 5.6 mumol/mmol (range 10.6-34.7). Finally, we compared in the same urinary samples hydroxyproline excretion with pyridinoline excretion (hydroxylysylpyridinoline and lysylpyridinoline), a new marker of bone resorption. The values show a significant correlation, with r = 0.417 for hydroxylysylpyridinoline and r = 0.443 for lysylpyridinoline.

Aged↗
PubMed1995

Multiple molecular forms of pyridinolines cross-links excreted in human urine evaluated by chromatographic and immunoassay methods.

The measurement of the collagen cross-links, hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP), excreted in urine either in free or peptide-bound forms represents the most extensively investigated biochemical marker of bone collagen degradation. We studied the urinary molecular forms of pyridinolines after separation in free and peptide-linked fractions by chromatography and serial dialysis. The pyridinoline amounts of molecular species (free, < 1000 D, 1000-3500 D, 3500-10,000 D, and > 10,000 D) were evaluated by high performance liquid chromatography (HPLC) as well as with the two newly introduced enzyme-linked immunosorbent assay (ELISA) methods for determination of free pyridinolines (collagen Pyrilinks and collagen Pyrilinks-D). The variability of urinary pyridinoline forms were studied in healthy adult control subjects (n = 10, 38.4 +/- 7.5) years), in adolescents (n = 10, 16 +/- 3.3 years), and in elderly subjects with vitamin D insufficiency (n = 10, 87.3 +/- 4.3 years). Free and peptide-conjugated pyridinolines with MW < 1000 D constitute the major part of urinary cross-links in all groups, with a significantly lesser excretion in elderly patients than in adolescent groups. Expressed as a percent of total cross-links, urinary free pyridinolines assessed by direct HPLC are less in elderly subjects (HP = 34.2 +/- 6.2%, LP = 32.7 +/- 7.6%) than in adolescents (HP = 45.8 +/- 10.8%, p = 0.0065 and LP = 47.8 +/- 12.1%, p = 0.012) and in healthy adults (HP = 39.3 +/- 11.5%, NS and LP = 38.1 +/- 9.3%, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Markers of bone remodeling in the elderly subject: effects of vitamin D insufficiency and its correction.

The elderly subject is prone to both vitamin B insufficiency and calcium insufficiency due to a low calcium intake and calcium malabsorption. These two alterations may lead to secondary hyperparathyroidism, and thus to increased bone loss. We investigated 72 elderly subjects (16 men and 56 women) with vitamin D insufficiency and 25 healthy elderly women with normal vitamin D status, with respect to their indices of calcium metabolism and of bone remodeling: serum total alkaline phosphates (phosphatases), bone AP (BAP), osteocalcin (BGP), tartrate-resistant acid phosphatase (TRAP), urine hydroxyproline (HYP), and the 3-OH-pyridinium derivatives pyridinoline (PYD) and deoxypyridinoline (DPD), which are new markers of bone resorption. We then studied the modifications of these markers in the patients with vitamin D insufficiency at 3 months and 6 months after onset of a daily vitamin D and calcium supplementation. When compared with elderly subjects with normal vitamin D status, patients with vitamin D insufficiency had increased intact parathyroid hormone (iPTH) levels (60.1 +/- 10.2 vs 30.2 +/- 4.5, p < 0.001) and a high bone turnover as reflected by increased values of most serum and urine markers of bone remodeling. PYD and DPD levels were significantly correlated with all indices of bone turnover, unlike HYP, which showed no correlation with bone formation markers (AP, BAP, and BGP). A daily supplement of 800 IU vitamin D3 and 1 g of elemental calcium increased 25(OH)D levels and induced a dramatic decrease of iPTH levels; at 3 and 6 months, the mean iPTH level decreased by 50% (p < 0.0001), reaching the mean value of healthy vitamin D sufficient elderly women. All markers of bone turnover, except TRAP, decreased significantly at 3 and 6 months. The PYD/DPD ratio increased significantly at 3 and 6 months. The decrease of bone markers was more marked in patients with more severe hyperparathyroidism, the greatest variations being obtained with BAP (45%, p = 0.006) and DPD (43%, p = 0.036) levels. Most markers of bone remodeling are increased in elderly subjects with vitamin D insufficiently and vary with its correction. However, BAP and DPD are the most sensitive indicators of increased bone turnover due to secondary hyperparathyroidism.

Aged↗
PubMed1995

Cytokine-mediated bone resorption in patients with the hyperimmunoglobulin E syndrome.

Hyperimmunoglobulin E syndrome (HIES) is a rare immunodeficiency disorder characterized by increased serum immunoglobulin E levels. Bone fragility is part of this syndrome, which has recently been reported to be also associated with an imbalance in cytokine-secreting lymphocyte subpopulation. It has recently been shown that some cytokines can play a role in the bone fragility following menopause. We therefore investigated six patients (mean age 16.5 +/- 8.5 years) affected by this rare syndrome in order to study their bone remodeling and the possible involvement of cytokines in causing the bone fragility associated with this disease. Three of six patients had suffered long bone fractures; in four of six patients the cortical bone mass measured at the distal radius was two standard deviations below that of the aged-matched controls. Urinary pyridinoline excretion, a marker of bone resorption, was markedly increased in the two youngest patients. Adherent mononuclear cells derived from these patients were cultured in vitro and the bone resorbing activity (BRA) of the culture supernatant was measured by means of a fetal rat long bone assay. The BRA was up to 28% above the basal value. We compared the BRA and the cytokine production by the mononuclear cells of these patients to that of postmenopausal women. The BRA, and the IL1 beta, IL6, and TNF alpha levels in the mononuclear cell culture supernatants were identical for both HIES and postmenopausal women. However, the levels of PGE2 were higher and the levels of interferon-gamma were lower in the HIES patients. In conclusion, increased bone resorption in young patients with the HIES is responsible for the cortical bone loss that leads to a higher incidence of fractures. The high BRA secreted by the mononuclear cells of these patients is similar to that found in mononuclear cells from postmenopausal women. These data provide evidence of potent mononuclear cell activation leading to bone loss in HIES, which could be related to IgE-dependent mechanisms.

Adolescent↗
PubMed1995

[Bone involvement in idiopathic calcium lithiasis].

Bone involvement in idiopathic calcium nephrolithiasis is characterized by the following abnormalities: a) the bone density is decreased, the severity of bone loss being dependent upon the existence of hypercalciuria and upon the pathophysiology of this latter: it is inconsistent in the absence of hypercalciuria or when hypercalciuria is of the absorptive type I or II, whereas it is almost constant in fasting hypercalciuria without secondary hyperparathyroidism and constant and severe in the rare true renal hypercalciuria. b) The bone histology (which has been evaluated only in idiopathic hypercalciuric patients) mainly shows a defect in bone formation at the exception of the rare renal hypercalciuria. Osteoclastic hyperresorption is only seen in this latter type of hypercalciuria whereas in the other types of hypercalciuria only an increase of the total or inactive resorption surface is observed. This phenomenon is possibly explained only by a delayed refilling of the resorption lacunae secondary to the decreased bone formation. The osteoid thickness is either normal or decreased despite decrease in mineralization apposition rate which seems therefore to be secondary to the decreased bone formation. c) Symptomatic bone disease in hypercalciuric stone formers is exceptional and always related to a severe long term calcium restriction. d) The biochemical markers of bone resorption tend to be increased in idiopathic hypercalciuria. Hydroxyprolinuria is more often elevated than pyridinolinuria. However pyridinolinuria is negatively correlated to bone density. The contrast between the increase of these bone resorption markers and the usual normality of plasma PTH and of the osteoclastic resorptive surfaces, suggest the role of meat induced acid load which may favor inactive resorption by dissolution of bone buffers. A disturbed profile synthesis of cytokines which induce differentiation and proliferation of the osteoclasts and which modulate the osteoblastic proliferation and function (IL-1, IL-6, TNF-alpha, GM-CSF...) may play a role in the bone loss of calcium stone formers but further studies are necessary to precise its transient or permanent involvement in their bone disease. e) The decrease of bone formation may be explained by the suppressed PTH secretion which may be explained by hypercalcitriolemia. This excess of calcitriol synthesis may be secondary either to monocyte increased synthesis of IL-1 which stimulates the renal 1 alpha-hydroxylase by the mean of an increased PGE2 synthesis or to the relative hypophosphatemia of the calcium stone formers comparatively to healthy controls. Hypercalcitriolemia may originate from the activated monocyte itself. The decrease in bone formation may also be secondary to the action of monokines on the osteoblast differentiation and/or function.

Animals↗
PubMed1995

Evaluation of a new solid formulation of calcium and vitamin D in institutionalized elderly subjects. A randomized comparative trial versus separate administration of both constituents.

Supplementation with 800 IU of vitamin D and 1 g of calcium each day is recommended in institutionalized elderly subjects to prevent secondary hyperparathyroidism and its adverse skeletal effects. An original formulation (IDEOS) combining vitamin D and calcium has been developed for use in this end. The aim of this study was to determine whether administration of this association, of which each tablet contains 500 mg calcium and 400 IU vitamin D3, produces the same beneficial effects on laboratory parameters as separate administration of both active agents. A multicenter randomized study was conducted in 91 elderly institutionalized subjects (mean age 83.1 years) who had vitamin D deficiency [25-(OH)D < 6 ng/ml] without severe renal failure. Subjects were randomly assigned to one of the two treatment groups. Treatment duration was six months. One group (G1, n = 46) received one tablet of the new formulation twice daily. The other (G2, n = 45) received 8 drops of vitamin D3 (800 IU/day) and one calcium carbonate 500 mg tablet twice daily. Blood tests were carried out at inclusion and after three and six months of treatment. In group G1, plasma 25-(OH)D levels increased from 2.6 ng/ml at inclusion to 14.6 ng/ml at month 6 (p < 0.001), and iPTH fell from 63.2 pg/ml at inclusion to 33.8 pg/ml at month 6 (p < 0.001). In group G2, 25-(OH)D rose from 2.8 ng/ml at inclusion to 13.5 ng/ml at month 6 (p < 0.001), and iPTH fell from 55.4 pg/ml at inclusion to 32.5 pg/ml at month 6 (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Prevalence and biological consequences of vitamin D deficiency in elderly institutionalized subjects.

The prevalence of vitamin D deficiency was evaluated in a population of elderly institutionalized subjects in seven long-term geriatric care facilities in France (Amiens, Francheville, Ivry, Lille, Montpellier, Oissel and Villejuif). Residents whose functional capability was relatively good were entered into the study. There were 126 patients (99 females and 27 males) with a mean age +/- SD of 84 +/- 6.6 years. All subjects had been institutionalized for over six months and were capable of walking at least as far as the dining room. None had received vitamin D or other compounds known to affect the metabolism of phosphorus and calcium within six months before the study. Vitamin D status was evaluated by determining serum 25 hydroxyvitamin D (25 OH D) levels using a radiocompetition assay after extraction and chromatographic separation. Mean serum 25 OH D was 3.17 +/- 2.52 ng/ml (median 2.5). Eighty-five per cent of subjects had serum 25 OH D values of less than 5 ng/ml and 98% had values under 10 ng/ml, which is the cutoff usually taken to define vitamin D deficiency. Mean serum levels of intact parathyroid hormone were increased approximately two-fold as compared with values in healthy adults (70 +/- 39 pg/ml versus 33 +/- 12 pg/ml). Biochemical markers for bone formation (alkaline phosphatase, osteocalcin) and bone resorption (TRAP, hydroxyproline, pyridinoline) were all increased, with mean values 1.4-fold to 3.4-fold those seen in healthy adults. Serum 25 OH D levels were negatively correlated with serum intact parathyroid hormone levels (r = 0.41; p < 0.0001). Serum intact parathyroid hormone levels were positively correlated with alkaline phosphatase activity (r = 0.30; p < 0.001) and serum osteocalcin levels (r = 0.36; p < 0.0001) and negatively correlated with corrected serum calcium levels (r = -0.20; p < 0.02). Conclusion. Our data demonstrate that severe vitamin D deficiency is present in virtually all elderly institutionalized subjects and is accompanied with secondary hyperparathyroidism responsible for increases in markers of bone remodeling. Routine vitamin D supplementation is warranted in elderly institutionalized subjects.

Adult↗
PubMed1994

Urinary excretion of pyridinolines crosslinks measured by immunoassay and HPLC techniques in normal subjects and in elderly patients with vitamin D deficiency.

Hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) are specific constituents of mature skeletal collagens excreted in urine. Their measurement represents a sensitive index of bone resorption. In this study, we have measured urinary excretion of pyridinolines crosslinks by immunoassay (ELISA) and HPLC methods in 80 patients with different bone resorption rates. We chose a sample of 44 healthy adults (30 men and 14 women) and a sample of 36 elderly patients (7 men and 29 women) presenting a secondary hyperparathyroidism due to a vitamin D deficiency. The correlation between HPLC (x) and ELISA (y) was judged satisfactory (y = 0.794x + 6.947, r = 0.92). The sensitivity of pyridinolines estimation was 50 nmol/l for immunoassay and 20 nmol/l for HPLC. The intra-assay and inter-assay coefficients of variation for the two analytical methods was < 10%. The mean excretion of crosslinks (nmol/mmol of creatinine) measured by both methods in the sample of healthy adults was higher in women than in men. The amount of pyridinolines crosslinks excreted by elderly patients with vitamin D deficiency are three time higher than those of normal adults when measured by ELISA and HPLC methods. The distribution of different molecular forms of urinary pyridinoline crosslinks was investigated. Values of pyridinolines measured by HPLC in our samples of elderly patients have shown that free and peptide-bound pyridinolines with molecular weight (mol. wt.) smaller than 1000 Da represent approximately 80% of the total pyridinolines contained in urinary samples. A study on the evaluation of the antiserum used in the immunoassay for reacting with the different molecular forms isolated from urine showed a high affinity for free and peptide-bound pyridinolines with molecular weight smaller than 10,000 Da and that do not react strongly with peptide-bound with molecular weight greater than 10,000 Da. We conclude that, although this immunoassay does not measure total pyridinolines and does not distinguish between HP and LP, it seems convenient for diagnostic of metabolic bone diseases.

Adult↗
PubMed1994

Evaluation of iodide deficiency in Togo using an optimized potentiometric method for iodide estimation in urine.

A pilot study was carried out in two Togolese localities (Gobe, Moretan) situated in an endemic goiter area. The aim of this work was to collect laboratory and nutritional data to assess and follow up campaigns against iodide deficiency. Ninety-seven urine samples were analysed. We studied the urinary excretion and the iodine concentration of important diet substances (water and salt) using an optimized potentiometric method. Mean values of urinary iodide/creatinine ratios (microgram/g) observed in the two Togolese localities were respectively 34.1 +/- 6.3 in Gobe and 39.2 +/- 6.4 in Moretan. These low values differ significantly (P < 10(-9)) from the physiological values determined in Amiens, France (147.5 +/- 56.3). The drinking water of the two localities showed a low iodide concentration (2 micrograms/l). The iodide concentration of cooking salts was also low (< 0.2 mg/kg) compared with iodized salt used in France (11.2 +/- 0.2 mg/kg) These results show an iodide deficiency in both localities, probably due to the lack of iodide in the local diet. Iodide determination is specific, easy and inexpensive. It can be proposed for use in campaigns against goiters of nutritional origin.

Adult↗
PubMed1992

High-performance liquid chromatographic determination of 3-hydroxypyridinium derivatives as new markers of bone resorption.

Hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) are intermolecular cross-linking amino acids of collagen and their urinary excretion reflects bone resorption. An isocratic high-performance liquid chromatographic assay using a reversed-phase column with a prefractionation step and fluorescence detection was developed. The accuracy and reproducibility were assessed by loading experiments and by double analysis of urinary samples. The recoveries after various loads were above 90% for HP and between 87 and 94% for LP, with an intra-assay relative standard deviation (R.S.D.) of 5% for HP and 8% for LP. The inter-assay R.S.D.s were 8% for HP and 12.4% for LP. The fasting and 24-h urinary excretions of HP and LP were measured in 40 healthy subjects (mean age 35 years) of both sexes. There was no difference between males and females. Mean adult normal values were 33.6 +/- 8.1 pmol/mumol creatinine for HP and 7.0 +/- 2.5 pmol/mumol creatinine for LP in morning fasting urine and 2-.9 +/- 7.0 pmol/mumol creatinine for HP and 5.8 +/- 1.9 pmol/mumol creatinine for LP after 24-h urinary collection. HP and LP excretions were significantly higher in morning fasting urine than in 24-h collections, in agreement with the physiological circadian rythm of bone resorption. This simplified and optimized procedure is a good method for the determination of pyridinolines and should be useful for the evaluation of bone resorption.

Adult↗
PubMed1992

Control of predialytic hyperphosphatemia by oral calcium acetate and calcium carbonate. Comparable efficacy for half the dose of elemental calcium given as acetate without lower incidence of hypercalcemia.

Since Mai et al. found, with the intestinal lavage technique, that the same dose of elemental calcium given as acetate (Ca Ac) complexed in the gut of uremic patients twice as much phosphate as calcium carbonate (CaCO3) while inducing a rather low calcium absorption, we wanted to see if half the dose of elemental calcium given as Ca Ac could control, on medium term, the predialysis plasma phosphate as well as CaCO3 while inducing less frequent hypercalcemia. This was evaluated in a cross-over study of 3 periods of 10 weeks according to the sequence Ca Ac, CaCO3 and Ca Ac, in 12 compliant patients on chronic dialysis previously treated by CaCO3. Because of poor tolerance of Ca Ac during the first period, 4 patients were excluded and the results were assessed only on the 8 patients who completed the study. For half the doses of elemental calcium (620 +/- 250 mg versus 1,310 +/- 560 mg versus 710 +/- 200 mg/day), Ca Ac allowed the same control of predialytic hyperphosphatemia (1.67 +/- 0.34; 1.74 +/- 0.32; 1.75 +/- 0.38) with paradoxically comparable normal mean plasma calcium concentration (2.61 +/- 0.14; 2.56 +/- 0.13; 2.55 +/- 0.14 mmol/l). Plasma alkaline phosphatases and intact PTH concentrations remained also stable during the 3 periods. The frequency of hypercalcemia greater than 2.75 mmol/l (12; 9; 20%) and of hyperphosphatemia greater than 2 mmol/l (17; 22; 27%) were comparable with the 2 treatments. In conclusion, Ca Ac controls predialytic hyperphosphatemia as efficiently as CaCO3 for half the dose of elemental calcium without, however, decreasing the frequency of hypercalcemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗
PubMed1991

[Fluoride bioavailability from sodium fluoride alone or in association with different calcium salts].

Fluoride pharmacokinetics were studied in twelve healthy subjects after oral administration of one tablet of osteofluor-containing 25 mg of sodium fluoride alone or associated with different calcium salts (500 mg Ca element) given as microcrystalline hydroxyapatite compound or powdered tri-calcium phosphate. Fluoride was measured in plasma and urine with a specific electrode and fluoride bioavailability from the three drugs was compared. Calcium absorption after oral load was assessed by measuring variations from the fasting state of plasma calcium and parathyroid hormone and of the urinary calcium to creatinine ratio. The bioavailability of fluoride is significantly decreased by the association to sodium fluoride of hydroxyapatite but not of tri-calcium phosphate. Calcium absorption seems greater after administration of hydroxyapatite compound. The decrease of the fluoride bioavailability is probably dependent on the capacity of calcium absorption from the calcium salts. The association of calcium to fluoride is absolutely required for treatment of osteoporosis. The microcrystalline hydroxyapatite compound seems preferable in view of its greater calcium absorption and of its limited decrease in fluoride bioavailability.

Administration, Oral↗
PubMed1991

Pharmacokinetics of butyric acid derivative with xylitol.

The short chain fatty acids, especially butyric acid salts have interesting biological properties. In some cases, transformed cells can recover a normal phenotype and in animal, butyrate salts increase antitumor resistance. Butyrate may be considered as possibly useful for antitumor therapy. But these products exhibit two essential disadvantages which restrict their clinical use in man: high concentrations required to achieve therapeutic effects and rapid excretion with short half life. In order to optimize the clinical use of butyrate, we studied a n-butyric acid ester obtained with xylitol selected for its physiological and metabolic inertia. Structure determination of tributyryl xylitol was carried out by mass and NMR spectrometry (MW = 344). The low toxicity and the antitumor effects of this ester, especially in association with Corynebacterium parvum and interferon, confirm its therapeutic interest. The slow excretion of this prodrug should make butyrate clinical use easier by preventing extensive systemic metabolism and metabolic side-effects due to cations of butyrate salts.

Animals↗
PubMed1990

A new series of antiarrhythmic procainamide derivatives: toxicity and activity-simulated passive absorption relation.

Several compounds derived from benzamidines and nicotinic pyridinic amidines with a structure similar to that of procainamide, exhibit notable antiarrhythmic properties after injection into animals. The diffusion rate of these different compounds through a solid lipidic artificial membrane was studied with Dibbern's apparatus. A statistical relation was established between the diffusion rate and the principal pharmacological parameters obtained after intraperitoneal injection (toxicity and anthiarrhythmic activity). Essential structural elements seem to determine a better bioavailability than procainamide: character of the substitution (in para) of the benzenic cycle; length of the lateral chain.

Absorption↗
PubMed1989

Pharmacokinetic study of butyric acid administered in vivo as sodium and arginine butyrate salts.

Considering that butyrate-treated malignant cells can recover in a transitory fashion a non-cancerous phenotype, the authors carried out a pharmacokinetics study of butyric acid injected as sodium or arginine salts for possible antitumor therapies. In the case of 1-14C-labelled butyrate, the appearance of radioactivity in the blood of injected mice is rapid and some of it is maintained for relatively long periods in different organs, mainly the liver. However, no precision can be given about the structure of radioactive compounds in blood and tissues. Using gas-liquid chromatography, the authors studied the metabolism of butyrate in both animals and man. In mice and rabbits, the half-life is less than 5 min. In man, the butyric acid elimination curve can be divided into two parts corresponding to two half-lives: for the first (0.5 min), the slope suggests an accelerated excretion, while for the following (13.7 min), a slow plateau is observed. The rapid elimination of butyrate is a limiting factor for practical applications. However, the lack of toxicity supports its use in human therapy.

Adult↗