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Biomedical subjects

R C Puche

Publications and source records attributed to R C Puche.

At least 19 recordsLinked to original sources
PubMed2001

Intestinal absorption of fluoride at high luminal concentration of fluoride.

The paper reports that high fluoride concentrations in the intestinal lumen hinders the absorption of this anion. This conclusion was verified with three different experimental models. Pharmacokinetic experiments done in human volunteers revealed that the bioavailability of fluoride from sodium fluoride (NaF, CAS 7681-49-4) enteric coated tablets was 33% of that of plain (immediate release) tablets. The latter findings were confirmed in rats receiving 1 ml of NaF solutions (40, 80 or 160 mmol/l) by gavage. The greatest AUC (area under the curve of fluoremia as a function of time) was obtained with an oral dose of 80 mumol of NaF. This parameter was significantly greater (p < 0.01) with 80 mumol than with 40 mumol NaF, but similar to that observed with 160 mumol. Fecal fluoride excretions (in the 24 h following a single dose of NaF) and the bone fluoride contents (found at the end of 30 days of treatment with 40, 80 or 160 mumol NaF/day), agreed with the AUC values. The rate of fluoride absorption (v, mumol/10 min) through the intestinal wall was investigated with perfused, isolated rat duodenum in vivo. Fluoride absorption increased between 0 and 10 mmol/l luminal fluoride and decreased with higher concentrations. Oxygen consumption of duodenal-tissue decreased exponentially between zero (1.12 mumol O2 min-1 g-1) and 10 mmol/l fluoride (0.45 mumol O2 min-1 g-1).

Adult↗
PubMed2000

Diet and nutrition of prehistoric populations at the alluvial banks of the Parana River.

This study attempts to characterize the health status and diet of prehistoric populations (1,000-2,000 years BP), dwelling at both banks of Parana River, between 29 degrees S and 32 degrees S. The data obtained suggest that these prehistoric populations had an adequate nutritional status, with complete proteins in the diet, as suggested by the ratio strontium/calcium in their bone mineral (0.71 +/- 0.04 microgram Srx1,000/mg Ca). The overall frequency of dental caries (4.9%) coincides with that reported for hunters-gatherers. The average mineral densities of the tibiae of adult subjects exhumed at two sites (males: 1.51 +/- 0.07 gr/cm2; females: 1.24 +/- 0.06 gr/cm2) suggested that they had significant bone mass, an asset compatible with adequate nutrition. In metacarpals, the amount of cortical tissue also suggests bone mass comparable to contemporaneous controls. The growth and development of the prehistoric populations studied are deemed normal as shown by the clear sexual dimorphism of their estimated heights at adult age (males: 177-183 cm; females 152-166 cm) and their bone mass.

Anthropology, Physical↗
PubMed2000

Effects of depot medroxyprogesterone acetate on the calcium metabolism of adult ovariectomized rats.

This paper describes experiments designed to test the effect of depot medroxyprogesterone acetate (DMPA) on calcium metabolism of adult ovariectomized rats. The 24 animals were randomly assigned to control or treated groups. Treated rats received 15 mg of DMPA i.m. per week, during four or twelve weeks. Controls received solvent alone. The variables characterizing the metabolism of Ca (daily rates of intestinal absorption and excretion, bone accretion and resorption and the sizes of the exchangeable pools and their rate constants) were measured with the aid of 45Ca according to Aubert and Milhaud. No effects were observed at four weeks of treatment. After twelve weeks, treatment produced serum levels of 46.5 +/- 5.6 nmoles of medroxyprogesterone/L, reduction of bone turnover (Ca accretion and resorption rates) and of the size of the slow exchanging Ca compartment. The increase in true Ca intestinal absorption was compensated by the increased endogenous fecal Ca excretion. The mass of body Ca was not affected by treatment.

Animals↗
PubMed1999

Metabolism of the complex monofluorophosphate-alpha 2-macroglobulin in the rat.

Sodium monofluorophosphate (MFP) is a drug used in the treatment of primary osteoporosis. Following the intake of MFP, a small fraction of the drug is absorbed intact and forms a complex with alpha 2-macroglobulin (MFP-alpha 2M) inactivating the antiproteasic activity of the globulin. The complex has been shown to occur in the serum of rats and human being. This paper reports data on the metabolism of this complex in the rat. In vitro experiments showed that liver and bone tissue remove MFP-alpha 2M from the incubation medium. When the experiments were pursued beyond the time needed to reduce the complex concentration to very low levels, fluorine (F) reappears in the medium in two forms: bound to low molecular weight macromolecule/s (2,200 +/- 600 Da) and as ionic F. Concentrations of these F fractions increase while that of the complex decreases as a function of time. In vitro, uptake of the complex by liver or bone tissue was not affected by the presence of colchicine or methylamine. These drugs, however, inhibited intracellular metabolism of the complex, as indicated by the impairment of the return of F species to the extracellular space and the increase in F content of the tissue. The cellular receptors responsible for the uptake of the complex in liver and bone are insensitive to low concentration of calcium and inhibited by polyinosinic acid[5']. These features characterize the "scavenger" receptor, one of the two receptor types known to remove inactive alpha 2M from the circulation. Injection of polyinosinic acid [5'] to living rats also hindered the disappearance of the complex from serum. It is concluded that the metabolism of the MFP-alpha 2M complex involves binding to receptors, uptake by cells, lysosomal degradation and return of F bound to low molecular weight macromolecule/s to the extracellular space. It is assumed, however, that inorganic F is the final product of lysosomal hydrolysis of the protein moiety.

Animals↗
PubMed1999

In postmenopausal osteoporosis the bone increasing effect of monofluorophosphate is not dependent on serum fluoride.

According to previous pharmacokinetic studies the bioavailability of fluorine (F) from sodium monofluorophosphate (MFP) doubles that of sodium fluoride (NaF). This paper reports a study designed to verify whether the vertebral bone mass increasing effect of NaF (30 mg F/day) was comparable to that of MFP (15 mg F/day), given for 18 months to osteoporotic postmenopausal women. The BMD of lumbar vertebrae of both groups showed significant increases (MFP: 60 +/- 15 mg/cm2, NaF: and 71 +/- 12 mg/cm2) over basal levels (P < 0.001). The difference between treatments was not significant (P = 0.532). The serum levels of ionic F (the mitogenic species on osteoblasts) were not related to the above mentioned effects. In NaF-treated patients, the fasting levels of total serum F increased significantly (6.7 +/- 0.9 microM vs. Basal: 2.0 +/- 0.8 microM; P < 0.001). This phenomenon was accounted for by ionic fluoride that increased over 20-fold (6.5 +/- 1.9 microM vs. Basal: 0.3 +/- 0.04 microM). In MFP-treated patients the fasting serum levels of total (7.0 +/- 0.7 microM vs. Basal: 2.2 +/- 0.9 M) and diffusible F (0.5 +/- 0.02 microM vs. Basal 0.2 +/- 0.02 microM) increased significantly (P < 0.001). The increase in the non diffusible F fraction is accounted for by protein-bound F, probably by the complexes formed between MFP and alpha 2-macroglobulin and C3. Serum diffusible F was formed by two fractions: ionic F and F bound to low molecular weight macromolecule/s (2,200 +/- 600 Da), in approximately equal amounts. The general information afforded by the present observations support the hypothesis that ionic F is released progressively during the metabolism of MFP bound to alpha 2-macroglobulin and C3. These phenomena explain why comparable effects to those obtained with 30 mg F/d of NaF could by obtained with one half the dose of MFP.

Bone Density↗
PubMed1999

Measurement of total and diffusible serum fluoride.

This article describes a technique for the measurement of total and diffusible F content of serum, at clinical significant concentrations of F (1-10 microM). The proposed procedure avoids the interference of unknown serum components with the ion-specific electrode. Sample F is concentrated fivefold through distillation of hydrofluoric acid (Taves' method). Ionic fluoride is presented to the electrode in a simple solution at concentrations within the linear response of the electrode. Average recoveries of F from serum or its ultrafiltrate were 96+/-7% (21%) and 97+/-12% (53%) (mean+/-SEM [CV]), respectively. With four replicates of each sample, the technique produce within-run standard deviations of 0.6 microM and 2.2 microM at 1 and 10 microM F, respectively. Total precision assessment gave standard deviations of 0.6 microM and 2.6 microM at 1 and 10 microM F, respectively. The fasting serum F levels of normal climacteric women, 45 to 65 years, showed an asymmetric distribution. The data obtained started at the detection limit of the technique (0.1 mM). The 75 percentile was 1.85 microM for total and 0.5 microM for diffusible F. In patients (n = 25) treated with NaF (30 mg F/day) the fasting levels of total serum F (4.5 +/-1.7 microM) did not differ from those of diffusible F (4.2+/-1.5 microM). In patients (n = 50) treated with sodium monofluorophosphate (15 mg F/day) the fasting levels of total and diffusible serum F were 6.5+/-1.7 microM and 0.5+/-0.03 microM, respectively. In conclusion, this paper establishes the presence of two fractions of serum fluorine: diffusible and nondiffusible (or protein bound) and describes a technique for their clinical estimation. In untreated subjects and in patients receiving NaF, the former fraction contains ionic fluoride. In patients treated with MFP, diffusible serum fluorine is composed by ionic fluoride and low molecular weight, peptide-bound, acid-labile fluorine.

Aged↗
PubMed1997

Binding of monofluorophosphate to alpha2-macroglobulin and C3.

After administering an oral dose of monofluorophosphate (MFP) to human beings or rats, a fraction of the drug appears in plasma that is bound to proteins, establishing a previously undetected compartment of nondiffusible fluoride. This article documents experiments performed in vitro, describing the binding of MFP to two plasma globulins: alpha2-macroglobulin and C3 (a beta-globulin). MFP binds irreversibly to these proteins through a stable bond. MFP binds to purified alpha2-macroglobulin or to C3 with a molar ratio MFP: protein close to unity. MFP binding reduces significantly the biological activity of these proteins, which share in common a macrocyclic 4-residue ring thiolactone (Cys-Gly-Glu-Glu). The binding site of MFP is as yet unknown. Protein-bound MFP appeared in the plasma of volunteers during the 5-7 hours following intake. Peak concentration of protein-bound MFP and maximal reduction of alpha2-macroglobulin activity was observed 2 hours after intake. Clearance of protein-bound MFP coincided with the return of alpha2-macroglobulin to basal levels.

Animals↗
PubMed1997

Relative weight of glucose, insulin and parathyroid hormone in the urinary loss of phosphate by chronically diabetic rats.

This report deals with the relationships between glucose (G) and insulin on the tubular transport of phosphate (P) in chronically diabetic rats with high plasma levels of parathyroid hormone (PTH). Alloxan-induced diabetes leads to phosphorus depletion of the soft tissues. This phenomenon appears associated with weight loss and negative P balances caused by the increased urinary P excretion. Administration of 2 IU of insulin/100 g body weight (bw) to diabetic rats normalized their P balance and body weight. The effect of parathyroid function on the P metabolism of diabetic rats was investigated with balance experiments. Diabetic rats, intact or thyroparathyroidectomized (TPTX), have a greater urinary excretion of P than their controls. However, in control rats, the ratio intact:TPTX for urinary P is 1.0:0.76, showing the antiphosphaturic effect of parathyroid ablation. For diabetic animals, on the other hand, the ratio is 1.0:1.44. The simultaneous deficit of insulin and PTH thus quadruples the urinary P loss, instead of compensating for each other. The contribution of insulin deficit and hyperglycemia to the defect in tubular reabsorption (TRP) was investigated with clearance experiments (done on anesthetized, perfused rats). Five experimental groups were used: Controls (C), diabetics (D), controls + glucose (C + G), diabetics + insulin (D + I) and diabetics + insulin + glucose (D + I + G). All experimental groups showed a linear relationship between the TRP of P and G. The regression equation for C is significantly different (F = 40.1, P < 0.001) from that of D animals. The slope value measure the number of mumoles of P per mumol of G reabsorbed. For C and D rats, the ratio P:G approximates 1:4 and 1:20, respectively. The increase in P:G ratios represents the competition between both substrates for tubular resorption. Glycemias up to 11 mM (C and D + I) exist concurrent with the P:G ratio 1:4 Glycemias above 25 mM (D, C + G and D + I + G) produce a P:G ratio of 1:20. Fractional excretion of P (FEP) increased significantly in untreated, chronically diabetic rats (0.47 +/- 0.12 vs controls = 0.05 +/- 0.01, P < 0.001). After a single intramuscular injection of insulin, the FEP decreased as a function of insulin levels. To normalize the FEP of diabetic rats in short-term experiments, insulin had to be administered in doses that produce plasma insulin levels 25 times greater than normal. The general information afforded by the present experiments shows that in untreated, chronically diabetic rats, insulin deficit plays an indirect role. The absence of PTH enhances the effect of hyperglycemia. The latter and the concurrent tubular overload of glucose are the cause of hyperphosphaturia in these animals.

Animals↗
PubMed1997

Outcome of hip fractures among elderly subjects.

This paper reports a retrospective study (1979-1995) on 200 patients (154 women and 46 men), 50-101 years old, who received medical attention because of unilateral hip fracture. Nine women and four men fractured twice. In 75% of women and 90% of men, surgery was carried out between one and five days after fracture. A non significant greater proportion of women (14/154) than men (6/46) died in the first year after injury (chi 2 = 3.459, P = 0.062). Survival was assessed using Cox proportional hazards model. Survival was a function of age (P = 0.000) and sex (P = 0.008). After adjustment to a common mean age (79 years), the median survivals for men and women were 3.9 and 8.4 years, respectively. Controlled concurrent life-threatening diseases, the kind of fracture [medial (subcapital and transcervical) or lateral (inter- and subtrochanteric)] and the type of prosthesis (total/partial articulation replacement) had no significant impact on survival. No differences in evolution were observed: 80% returned to their ambulatory status before injury, 8.5% required walking aids and 5.5% could not walk. The overall information afforded by this study suggests that with worldwide improvement of hip fracture outcome, the cost/effectiveness of surgical treatment of hip fracture may become, from the standpoint of public health investment, a favorable alternative with respect to cost/effectiveness of prevention-treatment measures.

Aged↗
PubMed1996

Bioavailability of fluoride administered as sodium fluoride or sodium monofluorophosphate to human volunteers.

This paper reports a reassessment of the bioavailability of fluoride from monofluorophosphate (MFP, CAS 10163-15-2). It was prompted by recent work from this laboratory reporting that, following an oral dose of MFP, a fraction of the drug appears in plasma bound to globulins forming a previously undetected compartment of non-diffusible fluoride. The presence of protein-bound MFP in plasma after the intake of this drug hinders its straightforward comparison with NaF (CAS 7681-49-4). After an oral of NaF, all plasma fluoride is diffusible. After intake of MFP, on the other hand, plasma contains diffusible fluoride and protein-bound fluoride during the 6-8 h following intake. The area under the curve of total plasma fluoride for MFP (1540 +/- 117 mumol.min/l) doubles that of NaF (811 +/- 52 mumol.min/l p < 0.001). On this basis, in agreement with findings previously reported for the rat, it is concluded that the bioavailability of fluoride for MFP doubles that of NaF.

Adult↗
PubMed1995

The natural history of kyphosis in postmenopausal women.

A cross-sectional study of vertebral morphometry in 449 unscreened postmenopausal women, from the ages of 40 to 80, is reported. The wedge angles of thoracic vertebrae T4-12 were found to increase exponentially as a function of age, up to 70 years. In addition to age, the wedging phenomenon was found to be accentuated by increased bone turnover due to low calcium intake, reduced physical activity, each successive delivery, and breast feeding. Most of these variables were not correlated with isolated vertebral wedge angles, but rather with the sum of them (Sigma, sigma), assumed to assess the impact of those variables on thoracic kyphosis. In a subset of women, sigma was found to be inversely correlated with low spinal mineral density at L2-4. T-11 and T-12 were the vertebrae most frequently deformed (wedge angle exceeding mean +/- 3 SD in a group of 50 young healthy women, 25-45 years old). The distribution of deformed vertebrae was found to be significantly different from those qualified as "fractured" according to Kleerekoper et al.'s (1984) and Melton et al.'s (1989) criteria. The overall information afforded by past and present data indicates that in postmenopausal women, vertebral deformation may occur with the help of mechanical solicitations plus high bone remodeling rates, as well as by structural collapse (fracture). The information obtained does not allow one to quantify the relative contribution of each set of factors to the wedging phenomenon.

Adult↗
PubMed1995

Comparative study of the effect of sodium fluoride and sodium monofluorophosphate on glucose homeostasis in the rat.

The effect of acute and chronic administration of sodium fluoride (NaF) or sodium monofluorophosphate (MFP) on the glucose homeostasis of the rat are compared. The oral administration of a single dose of 40 mumol/100 g b.w. of either compound produced similar increases in plasma glucose (up to 1.8 g/l) and diffusible fluoride (up to 130 mumol/l). In long-term experiments (three months of duration), treatment with NaF (a 5 mmol/l solution as the water supply) produced, in the first month of experiment, abnormal glucose tolerance tests and increased plasma diffusible fluoride levels (range: 2-12 mumol/l). Treatment with MFP, on the other hand, did not affect glucose homeostasis; plasma diffusible fluoride was always below 2 mumol/l. The results of these experiments indicate that glucose homeostasis is affected when plasma diffusible fluoride exceeds 5 mumol/l. The basal and glucose-stimulated insulin secretion of isolated Langerhans rat islets (incubated with solutions containing 2, 5, 10 and 20 mumol/l NaF) was significantly inhibited by 5 to 20 mumol/l fluoride. No effect was observed under similar conditions with MFP at concentrations of 2, 5, 10, 20 and 50 mumol/l.

Animals↗
PubMed1994

An articulated rotating brush for office endometrial evaluation of climacteric outpatients.

This paper reports the experience obtained in the last 8 years with an instrument (articulated rotative brush) that allows access to the entire endometrial surface, obtaining material for both histological and cytological study. The latter has the advantage of reducing the number of cases in which insufficient material frustrates endometrial assessment. In addition to the overall experience gained with this instrument, the proportion of agreement with anatomo-pathological diagnosis after hysterectomy in 61 patients was high (96%) and the unweighted kappa statistic (0.862) indicated very good accordance between these techniques. Comparison between the present method and hysteroscopic observations in 84 patients with perimenopausal bleeding revealed a general conformity of 0.65 and an unweighted kappa statistic of 0.368 (fair agreement). In a group of 72 cases with postmenopausal bleeding a general conformity value of 0.92 was obtained, with an unweighted kappa statistic of 0.84 (very good agreement). In 90% of the cases the procedure was well accepted. In 57.3% of the cases, no difficulties were encountered using the brushing technique; in 25.9% slight dilatation was deemed necessary, whereas in 16.8% technical difficulties could not be overcome and general anesthesia was indicated. A total of 769 outpatients were investigated, 75.3% of which had normal endometria, 12.7% benign hyperplasias, 2.6% precursor lesions, 1.7% suspect carcinoma, and 4.2% carcinomas. Insufficient material for diagnosis occurred in 3.5% of cases tested. The combined cytohistological and hysteroscopic assessment of the endometrium provides satisfactory results in the etiological diagnosis of peri and postmenopausal bleeding, and in the follow up of patients undergoing hormonal replacement therapy (HRT).

Adult↗
PubMed1994

Gastric and intestinal absorption of monofluorophosphate and fluoride in the rat.

This paper reports data indicating that, in the rat, sodium monofluorophosphate (MFP, CAS 10163-15-2) is absorbed without hydrolysis through the stomach. This phenomenon and the fact that MFP binds to plasma globulins produce a prompt increase in protein-bound MFP concentration, significantly greater than the increase in plasma ultrafilterable fluoride. Intestinal absorption of MFP was investigated with the isolated duodenal loop in situ. The drug was hydrolyzed to fluoride at the intestinal lumen with a rate of approx. 3 times greater than that for fluoride absorption. After filling the duodenal loop with a MFP solution, ultrafiltrable fluoride accounts for the increase in plasma fluoride concentration, with no evidence of protein-bound MFP. This report also includes analytical techniques for the measurement of MFP in test solutions and in plasma.

Animals↗
PubMed1994

Pharmacokinetic differences between sodium fluoride and sodium monofluorophosphate and comparative bone mass increasing activity of both compounds in the rat.

After the administration of an oral dose of 80 mumol/l of NaF (CAS 7681-49-4) to rats, the area under the curve of total plasma fluoride equals 10,200 mumol.min/l. After an oral dose of 80 mumol of monofluorophosphate (MFP/CAS 10,163-15-2), two forms of fluoride appear in plasma: protein-bound MFP and diffusible fluoride. The areas under the curve of total (protein-bound + diffusible) and diffusible fluoride equal 22,200 and 8,850 mumol.min/l, respectively. The activity of MFP for increasing the bone mass of the rat was assessed with NaF as the standard. The animals were treated chronically for 100 days since weaning with food ad libitum and 5 mmol/l NaF, 5 or 2.5 mmol/l MFP solutions as the water supply. The effect obtained with 2.5 mmol/l MFP was similar to that produced by 5 mmol/l NaF, indicating a potency ratio MFP is twice as active as NaF.

Animals↗
PubMed1993

Hypercalciuria and urinary saturation measurements in climacteric women.

Fifteen percent (20/130) of a group of climacteric women on diets of their choice had urinary calcium (Ca) levels exceeding 4 mg/kg per day. Most of these hypercalciuric subjects had a daily Ca intake of 0.4-0.5 g. Their bone turnover rates were raised and high Ca absorption was observed in 4 cases. Serum Ca and total protein and glomerular filtration rates were normal in all the hypercalciuric patients. The calcium/creatinine (Ca/Cr) ratio (mg l-1/mg l-1, fasting, 09:00-10:00 h) was measured in 72 climacteric women, 35 of whom (49%) had ratios > 0.1. The latter defines a relative hypercalciuria as compared with premenopausal Ca excretion levels. Only 5 of the 35 subjects had calciuria levels above 4 mg/kg per day. The Ca/Cr ratio cannot replace daily urinary Ca measurements for the screening of subjects in whom calciuria may exceed net Ca absorption. Urinary saturation measurements were carried out in 70 women. Supersaturation was observed only in the case of Ca oxalate (CaOx) among several calcium salts usually found in urinary stones. CaOx supersaturation was observed in 95% of the hypercalciuric subjects and in 48% of the rest of the women investigated. The relatively high frequency of CaOx supersaturation can be attributed in part to the decreased excretion of citrate associated with ovarian failure. Oestrogen replacement therapy increased citrate excretion and lowered the level of CaOx supersaturation. Ca supplementation (1 g Ca/day) reduced the degree of supersaturation as a result of the concurrent reduction in oxalate excretion.

Absorption↗