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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
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↗
PubMed1993

Growth and development of bone mass in untreated alloxan diabetic rats. Effects of collagen glycosylation and parathyroid activity on bone turnover.

Body and skeletal growth and development were studied in alloxan-treated and age-matched control rats, between 3 and 23 weeks of age. For both groups the growth of the skeletal and body weights were in phase, with a maximum at 7 weeks of age. The growth data was assessed according to Parks' theory of feeding and growth. Alloxan-treated rats showed an important reduction in body and bone mass, with a greater impact on soft tissues. As expected, the asymptotic body and skeletal weights were reduced respect to controls. The time needed to attain 63% of mature food intake (Brody's 'time constant') was also reduced, indicating that maturation occurred at an earlier age than controls. The diabetic state is characterized by a reduced food conversion efficiency. Despite hyperfagia, alloxan-treated rats showed circa one-half the body and skeletal weights of age-matched controls. The following adverse effects of alloxan diabetes on bone tissue were observed: (a) a decrease in trabecular bone volume (femoral metaphyses) and cortical width (femoral diaphyses), (b) increased bone collagen glycosylation as a function of extracellular glucose concentration, (c) increased resistance of bone collagen to collagenase hydrolysis, (d) decreased rate of bone resorption except under strongly stimulated parathyroid function, (d) significantly lower ashes/bone matrix ratio in diabetic rats with more than 10 weeks of diabetes, and (e) no histological evidence of osteomalacia.

Alloxan↗
PubMed1993

Increased fractional excretion of sulphate in stone formers.

This study was performed to determine urinary sulphate excretion in patients with renal stone disease. Stone formers showed a significantly higher fractional excretion of sulphate than control subjects; 80% of stone formers had fractional excretions > 0.26. No significant relationship was established between increased urinary sulphate excretion and any identifiable metabolic disorder, or the recurrence rate of stone episodes. The increase in fractional excretion of sulphate appears to be a more prevalent tubular defect among stone formers than has hitherto been reported.

Adult↗
PubMed1993

Altered calcium-binding ability of plasma proteins as the cause of hypocalcemia in lepromatous leprosy.

This paper reports a study performed on 10 lepromatous leprosy outpatients and on the same number of age- and sex-matched contacts. All of the lepromatous patients were hypocalcemic, but plasma levels of ionized calcium and the acid-base status were normal. The average daily food intake assessed through a questionnaire revealed adequate nutrition of patients and controls. Plasma proteins and 1,25-dihydroxyvitamin D3 and intestinal absorption of calcium were discarded as the causes of the hypocalcemia. In vitro experiments designed to investigate the effect of hydrogen ion concentration on the equilibrium between calcium ion and proteins revealed that, at normal pH values, plasma proteins from lepromatous leprosy patients bind a smaller fraction of total plasma calcium than those from controls. This phenomenon produces a normal concentration of ionized calcium that determines a normal parathyroid status as indicated by the normal urinary excretion of hydroxyproline and plasma concentrations of alkaline phosphatase (total and bone isoenzyme) and tartrate-resistant acid phosphatase.

Absorption↗
PubMed1992

Bone mass increase and glucose tolerance in rats chronically treated with sodium fluoride.

Female rats were treated with fluoride for 100 days (between 21 and 121 days of age) replacing the water supply with a 5 mM NaF solution. Bone mass was assessed by destructive physical and chemical measurements on the whole skeleton, that gave an overall view not reported previously. Bone mass (dry, fat-free weight of the skeleton/100 g of body weight) increased 7% (P less than 0.001) with respect to control animals. This phenomenon was equally evident in the head, the axial and the appendicular skeleton. Fluoride treatment did not affect the ratio ashes/organic matrix. Treated animals showed a subtle disturbance of glucose tolerance as shown by glucose tolerance tests. The disturbance was manifest as high plasma and soft tissue levels of fluoride during the period of bone mass increase. Glucose tolerance was normalized when the maximum bone mass was achieved and plasma and soft tissue fluoride returned to control levels.

Animals↗
PubMed1992

Relative importance of urinary sulfate and net acid excretion as determinants of calciuria in normal subjects.

In normal subjects fed western-mixed diets, in the fasting state, 39.6% of the variance of calciuria is accounted for by net acid excretion and 4% by sulfaturia. In the postprandial period, net acid accounts for 6.9% and sulfaturia for 11.8% of the variance of calciuria. As expected, after a load of ammonium chloride, net acid excretion exceeded the importance of sulfaturia (36.2% vs. 8.4%) and the opposite was observed after DL-methionine load (1.5% and 46.2%). A group of normal subjects fed vegetarian diets was also investigated. The excretion of the three variables measured were significantly reduced in this group when compared with that of the former group. In the fasting state the variance of calciuria was accounted mainly by net acid excretion (85.7%). In the postprandial state net acid (4.9%) and sulfate (2.2%) had much less importance as determinants of calciuria. It is concluded that in spite of their metabolic relationship, net acid and sulfate excretions are independent determinants of calciuria. The relative importance of each variable changes as a function of metabolic circumstances.

Acids↗
PubMed1991

Estimation of bone turnover in climacteric women by the whole body retention of fluoride.

This paper reports the measurement of whole body retention using fluoride (WBRF) as an estimator of skeletal turnover in a group of climacteric women that received an oral dose of 700 mumol of sodium fluoride. WBRF is defined as 100(1-(urinary fluoride/fluoride load)). WBRF was significantly correlated with whole body retention of 99m-Tc-methylene-diphosphonate, the serum levels of the bone alkaline phosphatase and the urinary excretion of hydroxyproline. WBRF values ranged from 20% to 95% and were affected by calcium intake and the urinary calcium excretion. In normal subjects with high turnover, the measurement of serum alkaline phosphatase activity and/or urinary hydroxyproline excretion helps to distinguish these cases from patients with metabolic bone diseases due to metastases, Paget disease, etc. The fact that the fraction of fluoride not incorporated into bone is not further metabolized plus the accuracy, preciseness and rapidity of fluoride measurements in urine are the main advantages of this technique.

Alkaline Phosphatase↗