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Biomedical subjects

R C Puche

Publications and source records attributed to R C Puche.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Inhibitory effect of fluoride on the secretion of insulin.

The oral administration of sodium fluoride (NaF) (40 mumol/100 body weight [bw]) to fasting rats produced an immediate fall in insulin levels and the consequent increase in glycemia. These phenomena were observed with plasma fluoride concentrations 5-15 microM. Glycemia and insulin returned to normal levels within 4-5 hours, together with the washing out of fluoride from plasma and soft tissues. The insulin secretion of isolated Langerhans islets, perifused with solutions containing 5, 10, or 20 microM fluoride, was found to be significantly inhibited as a function of fluoride levels, both with basal and stimulatory concentrations of glucose. One hour after the intake of 60 mg of NaF, fasting human volunteers showed increased fluoride (5-15 microM) together with a significant fall of plasma insulin levels.

Administration, Oral↗

Calcium metabolism of rats with varying degrees of insulinopenia.

This paper reports an investigation designed to determine the influence of varying degrees of insulinopenia upon the calcium metabolism of actively growing, alloxan-treated rats fed diets with three levels of calcium. A significant reduction in the skeletal mass (in absolute terms) was observed one month after alloxan administration in rats fed diets with normal or high calcium contents. The impact of insulin deficiency was greater on bone collagen than on the mineral mass, as shown by the increased calcium/hydroxyproline ratio. Alloxan-treated rats showed rather increased levels of PTH which was at variance with respect to control animals and unrelated to the calcium content of the diet. In spite of the high PTH levels, diabetic rats showed significantly diminished rates of bone Ca accretion and resorption. In addition, the animals fed the diet with the normal Ca content, showed significantly reduced areas of osteocytes lacunae and hypocalcemia after 24 h of fasting. The overall information obtained indicates that, in the rat, insulin deficiency more pronouncedly affects organic matrix than mineral turnover. The diabetic state is characterized by an impaired response of bone tissue to physiological stimuli, which is attributed to defective cellular activity caused by insulin deficit. Diminished bone resorption is considered to be an adaptative response to preserve bone mass.

Alloxan↗

A clinical test for calcium absorption in climacteric women. A two tracer, single blood sample procedure with corrections for body size and skeletal turnover.

This paper reports a two tracers (45Ca for estimating calcium absorption and stable fluoride for assessing skeletal turnover), single blood sample procedure that estimates the absorption of calcium in climacteric women. The proposed technique determines the percentage (Ac) of the dose of 45Ca administered orally (in the fasting state, diluted with 150 ml of milk), present in the extracellular fluid (estimated as 15% of body wt) five hours after intake, corrected for skeletal turnover (assessed by the whole body retention of fluoride). In a series of 13 patients, Ac has been found to be operationally equivalent to the ratio: net Ca absorption/Ca intake, measured under balance conditions. The calcium balances of 60 climacteric women, estimated as: net Ca absorption (Ca intake factored by Ac) minus calciuria was found, as expected, to be correlated with skeletal turnover.

Body Weight↗

Growth and development of the bone mass of two strains of inbred rats.

The experiments reported in this paper were designed to gain information on the growth and development of the bone mass of the rat and to recognize genetically determined features of the growth phenomenon. The experimental model involved the study of the axial (AX, head excluded) and appendicular (AP) skeletons of two strains of inbred rats ('m' and 'e') from the 3rd to the 27th week of age. The contribution of the skeleton to body weight differed between strains ('m' greater than 'e'). The development of the skeleton was in phase with body growth (peak growth rate = 7th week of age). The AP skeleton of these strains of rats differed in the kinetics of matrix mineralization ('m' faster than 'e') and in the ash/matrix ratio of adult animals ('m' greater than 'e'). The AX skeleton, on the other hand, showed a constant ash/matrix ratio from the 4th to the 27th week of age, without significant differences between strains. The anatomical volume of the femur was found to differ significantly between strains at an earlier age (4th week) than its dry weight (7th week). The AP and AX skeleton of 'e' rats mature simultaneously attaining their peak calcium mass at 36 weeks of age. The maturation of the AP and AX skeletons of 'm' rats, on the other hand, are dissociated and attain full maturity at approximately 39 and 57 weeks, respectively. The curves of specific growth rates (g of Ca (or matrix) per week/g of skeletal Ca (or matrix] of the AP and AX skeletons indicate that there exist separate metabolic controls for the growth of Ca and matrix masses. Absolute measurements (Ca, organic matrix, ash or total dry weights, bone volume) unambiguously established that 'm' rats have greater bone mass than 'e' ones. Relative measurements favoured 'm' (ash/matrix ratio of AP skeleton), 'e' (femoral weight/volume ratio, percentage of metaphyseal trabecular bone volume) or gave no significant differences between strains (ash/matrix ratio of AX skeleton). These results indicate that the AP and AX skeletons have important metabolic differences and that their growth and development are under genetic control.

Aging↗

A correlation and path coefficient analysis of components of calciuria in normal subjects and idiopathic stone formers.

The composition of 24 h urine samples collected by 50 normal controls and 76 stone formers (30 hypercalciurics, 13 hyperuricosurics and 33 patients without metabolic abnormalities) were studied. Statistically significant multiple regression equations were obtained between calciuria and the urinary excretions of sulfate, citrate, sodium and creatinine. The three former ions were selected as variables because they were assumed to affect the tubular fluid concentration of ionized calcium and interfere with the reabsorption of calcium. Urinary creatinine was included because it increased the statistical significance of the multiple regression equations; it is assumed to be a function of body size. The regression equations differed between both groups of subjects because stone formers excreted significantly more sulfate and less citrate than controls. The four factors considered (sulfate, citrate, sodium and creatinine) account for 28.3, 6.8, 7.3 and 26.4% of the total variation of calciuria of normal controls and 45.0, 2.6, 8.6 and 14.7%, respectively, for stone formers.

Adult↗

Maternal effects on the phenotypic expression of the skeletal store of calcium (bone mass) and related variables in the rat.

The phenotypic expression of bone mass and several related variables were investigated in the rat, assessing the differences and resemblances between two strains of inbred rats and their reciprocal hybrids. The data obtained indicated a strong influence of the maternal environment in the expression of total calcium mass and the rates of true calcium (Ca) absorption, endogenous fecal Ca excretion and bone Ca accretion. The simultaneous occurrence of maternal effects on characters obviously related, suggested that formation and maintenance of bone mass is accomplished by a series of specialized cellular functions, possibly regulated by a single genetic block. Maternal effects on bone mass and related variables appear to be determined in utero and are fully expressed at adulthood.

Animals↗

Adverse effect of 1,25-dihydroxycholecalciferol on erythrocyte precursors in the rat.

Administration of 1,25-dihydroxycholecalciferol (0.5 microgram/d/100 g body weight) to vitamin D repleted rats produced a significant decrease in the number of femoral marrow cells, specially in the erythroid line. Analysis of blood revealed slight anemia with reticulocytopenia. The survival time of 51-Cr-labelled red cells was unaffected by treatment, suggesting that bone marrow became unable to replace cells at a normal rate. The adverse effect on erythropoiesis appeared related to the degree of the concurrent hypercalcemia, which in turn depends upon the calcium content of the diet.

Anemia↗

The effect of 1 alpha, 25-dihydroxycholecalciferol on iron metabolism.

Chronic administration of hypercalcemic doses of 1 alpha, 25-dihydroxycholecalciferol to intact, vitamin-D repleted rats for 4 weeks, enhanced net intestinal absorption of iron and liver iron stores. Daily net iron and calcium absorptions were found to be significantly correlated in both control and treated rats. In duodenal loop experiments, pretreatment with 1 alpha, 25-dihydroxycholecalciferol reversed the adverse effect of high Ca/Fe ratio on iron absorption. The increased intestinal absorption of iron did not result in a change of serum iron levels nor of total iron binding capacity due to the enhanced incorporation of absorbed iron into liver ferritin. The curve of uptake of 59Fe into circulating red cells of treated rats suggested retarded release of the isotope from stores. The hypothesis is advanced that the systemic metabolic defect (tissue hypoxia, raised erythropoietin levels) produced by 1 alpha, 25-dihydroxycholecalciferol is responsible for the disruption of the physiological coordination between iron stores and intestinal absorption.

Animals↗