Search PubMedSearch

Biomedical subjects

M Dechaux

Publications and source records attributed to M Dechaux.

At least 19 recordsLinked to original sources

Protein kinase C activation causes inhibition of Na/K-ATPase activity in Madin-Darby canine kidney epithelial (MDCK) cells.

To evaluate the influence of protein kinase C (PKC) activation on Na/K-ATPase activity in MDCK cells, we studied the effect of phorbol myristate acetate (PMA) and two diacylglycerol analogues, oleoylacetylglycerol and dioctanoylglycerol, on the enzyme activity. Na/K-ATPase activity was determined by cytochemistry. PMA induced a time- and dose-dependent inhibition of Na/K-ATPase activity and at 100 ng/ml decreased the enzyme activity by 55% of the initial value. These effects were mimicked by oleoylacetylglycerol and dioctanoylglycerol, and were abolished by two inhibitors of PKC, 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine (H7) and sphingosine. A phorbol ester that does not activate PKC, 4 alpha-phorbol 12,13-didecanoate, did not inhibit Na/K-ATPase activity. PMA inhibition persisted in the presence of cycloheximide and actinomycin D but not in the presence of amiloride. Dopamine (10 microM) inhibition of Na/K-ATPase activity was abolished in a dose-dependent manner by sphingosine. Results suggest that in MDCK cells Na/K-ATPase is an effector protein for PKC and that dopamine inhibition of its activity may be mediated by PKC.

Amiloride

Primary distal tubular acidosis in childhood: clinical study and long-term follow-up of 28 patients.

The long-term follow-up of 28 patients with congenital primary tubular acidosis is described. Ten patients had affected siblings but no history of similar symptoms in the preceding generation. Deafness was associated in 14 patients and developed before 12 years of age. Deafness was present in all familial cases, and patients without deafness showed no familial incidence, suggesting the existence of two different entities. All patients had growth retardation, which was more severe in the older patients and was always markedly improved by alkaline therapy. Rickets was found in some patients but seemed related to vitamin D deficiency. Catch-up growth was limited to the first 2 years of therapy in patients treated before 2 years of age, but sometimes lasted longer in older patients. Of the 12 patients who reached adulthood, those without rickets achieved a normal height but the others did not. We believe that therapy should be continued throughout life because of the risk of nephrocalcinosis.

Acidosis, Renal Tubular

Renal effects of angiotensin II in normotensive subjects on short-term cilazapril treatment.

In 13 normotensive subjects on a normal sodium diet, we studied renal vascular, blood pressure, and hormonal changes induced by infusion of exogenous angiotensin II (Ang II) (5 ng/kg/min) during baseline conditions and after 5 days of cilazapril administration. In both conditions, Ang II elicited a slight pressor response accompanied by renal hemodynamic and hormonal changes that were similar. This suggests that hourly changes in Ang II concentrations and/or in Ang II receptor density after short-term administration of the angiotensin-converting enzyme (ACE) inhibitor cilazapril does not significantly affect renal vascular reactivity. In addition, these results also indirectly suggest that most of the renal effects of ACE inhibition are mediated through suppression of Ang II formation.

Adult

Evaluation of capillaries for ionized calcium measurements.

Commercially available capillaries containing calcium-titrated heparinate as an anticoagulant designed specifically for ionized calcium measurements in blood were tested with four serum pools with ionized calcium concentrations adjusted to 0.75, 1.25, 1.50 and 2.50 mmol/L. Although this is the best available anticoagulant for this purpose, the use of these capillaries induced a +/- 1% alteration of the original concentration around the titration level and changes of -2 to +10% at pathological values. The amount of heparinate released exceeded the recommended limit of 50 IU/mL of specimen with some variability (6% to 20%). Increasing the amount of anticoagulant with the objective of avoiding magnetic mixing did not seem to be a valid approach. Finally, Radiometer, IL and AVL capillaries gave the best available and acceptable results in terms of alterations in ionized calcium.

Blood Specimen Collection

Effects of prolactin on Na+K(+)-ATPase activity in the nephron during maturation in the rat.

The effect of prolactin (PRL) on renal Na+K(+)-ATPase was investigated in 7-d-old neonatal rats. Animals were treated by bromocriptine (Br; a blocker of endogenous PRL secretion), and the enzyme activity was compared with that of untreated controls. Na+K(+)-ATPase was determined in renal sections in the medullary thick ascending limb of Henle's loop and in the distal tubule by cytochemistry. In the distal tubule, Na+K(+)-ATPase activity was significantly lower in Br-treated animals than in controls (330 +/- 169 versus 558 +/- 146 pmol inorganic phosphate/mm/h, respectively); values did not differ in the medullary thick ascending limb of Henle's loop between Br-treated and control animals (132 +/- 74 versus 165 +/- 113 pmol inorganic phosphate/mm/h, respectively). In vitro effects of PRL were investigated by determining the enzyme activity after incubation of renal sections from Br-treated and untreated animals with different concentrations of PRL. Results suggest that PRL may affect renal Na+K(+)-ATPase activity in the distal tubule in the neonatal period but do not support a major role of PRL in the enzyme maturation.

Animals

Increased monocyte-dependent suppression of polyclonal activation of B lymphocytes from cystinotic children.

In infantile cystinosis the amino acid cystine preferentially accumulates in phagocytic cells, polymorphonuclear leucocytes (PMN) and monocytes, rather than in lymphocytes. We previously described functional abnormalities in the oxidative metabolism and locomotion of cystinotic PMN and monocytes. The present study shows an abnormal lymphocyte polyclonal activation as evidenced by a decreased immunoglobulin (Ig) production and generation of Ig-containing cells (ICC) in cultures of peripheral blood mononuclear cells (PBMC) from cystinotic children upon stimulation with pokeweed mitogen and Staphylococcus aureus Cowan I. However, monocyte depletion from cystinotic PBMC fully reconstituted Ig production and ICC generation, indicating: (1) the presence of an increased monocyte-dependent suppression on lymphocyte polyclonal activation, and (2) that the intrinsic ability of cystinotic lymphocytes to respond to polyclonal stimulation was preserved. The increased cystinotic monocyte-dependent suppressive effect was not mediated by prostaglandin E2 (PGE2) since its production by cystinotic PBMC upon polyclonal activation was not different from that of controls. In addition, the sensitivity of cystinotic lymphocytes to the immunosuppressive effect of varying concentrations of exogenous PGE2 was similar to that of controls. Finally, indomethacin and 2-mercaptoethanol, two agents able to scavenge hydroxyl (.OH) radicals, restored Ig production by cystinotic PBMC, suggesting a role for reactive oxygen species in the increased cystinotic monocyte-dependent suppression.

Adolescent

Preanalytical errors in ionized calcium measurements induced by the use of liquid heparin.

The use of heparin in a liquid form to measure ionized calcium (Ca++) in plasma or whole blood can induce preanalytical errors by dilution and by changing the original Ca++ value by binding or by re-equilibration with calcium in the anticoagulant solution. To quantify these errors, Ca++ was measured on serum pools under different sampling conditions. Incomplete syringe filling and specimen volume/syringe nominal volume ratio effects were tested. Syringes were rinsed with saline to yield pure dilution effects, with sodium heparinate to study binding and with calcium-titrated heparinate to evaluate 'calcium-distortion'. Detailed tables provide percentage error values for all sampling conditions. Dilution errors could reach -5% and binding was always important (-14 to -50%). Distortion was minimal around 1.25 mmol/L but could reach -4% for high and +8% for low Ca++ values. Errors increased when syringes were not filled to their nominal volume, especially with small-sized specimens.

Anticoagulants

In vitro evaluation of a heparinized blood sampler for ionized calcium measurement.

When ionized calcium measurements are needed urgently blood has to be sampled with an anticoagulant to allow rapid specimen processing. Heparinate salts cause a decrease in ionized calcium by binding which is clinically significant when the concentration exceeds 15 IU/mL of whole blood. The use of an anticoagulant in an aqueous state induces 'solution-dilution' errors. To avoid these two types of error the use of calcium-titrated sodium heparinate in a dry state has been proposed. However, in this situation the actual calcium concentration could be modified if its value were different from the titration level. This possibility has been studied using a commercially available sampler (Radiometer B-129). When the sampler was used as recommended, errors were non-significant around 1.25 mmol/L. There was a +3% increase for low (0.75 mmol/L) values and a -2% decrease for high (2.50 mmol/L) values. Incomplete syringe filling increased these errors.

Calcium

Use of calcium-titrated sodium heparinate for ionized calcium determination on plasma and whole blood (heparinized blood sampler B-129 Radiometer).

We report modifications of ionized calcium as observed on specimens collected in a commercially available sampling device (Radiometer B-129). When the sampler is used as recommended, errors are non-significant around 1.25 mmol l-1. There is a +3% increase for low (0.75 mmol l-1) values and a -2% decrease for high (2.50 mmol l-1) values. Incomplete syringe-filling increases these errors.

Blood Specimen Collection

[Atrial natriuretic factor in hemodialyzed children].

Indirect evidence suggest that volume overload is the major determinant of plasma atrial natriuretic factor (ANF) elevation in hemodialysis patients. Correlations between plasma ANF levels and extracellular volume (ECV) were investigated by simultaneously measuring both parameters in 30 pediatric hemodialysis patients (aged 1 to 17.5 years; 18 M, 12 F) 24 hours after a dialysis session. Plasma ANF was determined using a commercially available RIA (Amersham) after plasma extraction (SEP-Pack C18); ECV was estimated by determining the volume of distribution of inulin and expressing the result as the % of body weight. In hemodialysis children, ANF levels ranged from 43 to 427 pg/ml (versus 30-70 pmoles/ml in age-matched controls) and EVC ranged from 17 to 33% BW. A significant positive correlation was found between plasma ANF levels and ECV (r = 0.66; p less than 0.001). Patients who exhibited falls in blood pressure during the dialysis session had lower mean ANF and ECV values (133 +/- 90 pg/ml and 23 +/- 3% BW, respectively) than those who did not (211 +/- 123 pg/ml and 26 +/- 4% BW, respectively). Conversely, patients who needed chronic antihypertensive therapy had higher mean plasma ANF and ECV values (204 +/- 122 pg/ml and 26 +/- 4% BW, respectively) than those who did not (149 +/- 100 pg/ml and 23. 5 +/- 4.5% BW, respectively). In a small subgroup of patients who had repeated determinations, individual plasma ANF and ECV changes were closely matched and both parameters were well correlated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Quantification of renal Na-K-ATPase activity by image analysing system.

The localisation of renal Na-K-ATPase activity along the rat nephron by a cytochemical method, and its quantification by an image analysis system, are described in this paper. Frozen kidney sections were exposed to a trapping agent, the lead ammoniac-citrate-acetate complex (LACA), and to all the substrates necessary to the enzyme activity. The absorbance of the histochemical reaction product (precipitated in situ), proportional to the enzymatic activity, was then measured through the analysis of the grey levels of the transmitted image of the kidney section. This method was both sufficiently sensitive and technically simple to permit measurements of the enzyme in large numbers of tubules and to determine its activity in each region of the nephron. The Na-K-ATPase activity has been determined in the proximal convoluted tubule (PCT), the medullary thick ascending limb of the Henle's loop (mTAL), and the distal convoluted tubules (DCT) of the rat nephron. The Na-K-ATPase distribution shows an activity per millimeter tubule length higher in the DCT than in the mTAL and the PCT: 1,406 +/- 33, 823 +/- 64, and 350 +/- 71 pmoles Pi/tubule mm/h, respectively. In conclusion, the described method allows the segmental quantification of Na-K-ATPase activity at a cellular level and offers a precise approach to the analysis of this enzyme along the length of nephrons.

Animals

Glomerular function and microalbuminuria in children with insulin-dependent diabetes.

Renal function has been evaluated in 45 diabetic children (age 12.5 +/- 4 years) with a mean diabetes duration of 4.9 +/- 3.5 years. Glomerular filtration rate (GFR; inulin and creatinine clearances), renal plasma flow (RPF; PAH clearance), resting urinary albumin excretion (UAE) were measured and compared with indexes of metabolic control: Hb A1C and blood glucose values (mean, post-prandial and maximal excursion) on the same day. GFR (inulin clearance) and RPF were significantly increased in the diabetic group (171 +/- 31 and 778 +/- 172 ml/min per 1.73 m2) compared with controls (124 +/- 18 and 631 +/- 128 ml/min per 1.73 m2). Both parameters were strongly correlated (r = 0.73; P less than 0.001). Creatinine clearance was not correlated to inulin clearance. Hyperfiltration (inulin clearance above 160 ml/min per 1.73 m2) was noted in 61% of the patients and was independent of diabetes duration. Five diabetic children had a UAE level above 15 micrograms/min. No relationship could be established between UAE and any of the metabolic indexes; GFR was weakly correlated to HbA1C (r = 0.35; P less than 0.05), to mean (r = 0.37; P less than 0.05) and post-prandial blood glucose (r = 0.37; P less than 0.05). In contrast, there was a strong correlation between GFR and the maximal blood excursion (r = 0.62; P less than 0.001). The study shows that renal abnormalities can be detected with a high frequency in diabetic subjects characterized by both an early onset and a short duration of diabetes and suggests the need for a more systematic evaluation of renal parameters in this population.

Adolescent

Renal functional reserve in children with reduced renal mass: study by two dietary periods.

It has been suggested that the "renal functional reserve" (RFR) defined by the rise in glomerular filtration rate (GFR) after a protein load could disappear in patients with severe nephron loss but with a normal GFR. This study compared, in 17 children, inulin clearance (Cin) measured by the plasma inulin plateau at the end of two 14-day randomized periods differing in protein intake: 100% (low protein, LP), or 200% (high protein, HP) of recommended dietary allowances (RDA). Diets were aimed at maintaining food habits and energy intake. Compliance was assessed by records of the last 3-4 days, an interview with the dietician and by urinary nitrogen measurements. Mean actual protein intake was 109% (56%-139%) RDA for the LP period and 220% (163%-319%) RDA for the HP period. Cin did not change in 14 children with GFR below (n = 7) or within (n = 7) the normal range. Cin was higher in the HP period than in the LP period (+32, 50, 63%) in 3 children who had a 50% (single kidneys) or a 25% (sclerosed glomeruli) nephron loss. Non-responding children had a GFR below 105 ml/min per 1.73 m2. Nephron loss (70% sclerosed glomeruli) was estimated in only 1 child with no RFR. The results suggest that GFR measurement after prolonged dietary stimulation could help in evaluating the severity of nephron loss in children with normal or borderline GFR. The prognostic value of this test has to be confirmed by long-term follow-up.

Adolescent

Effects of acute cisplatin administration on renal ATPase activities and magnesium excretion of rats.

Male Wistar rats were killed 1, 2, or 4 days after a single intraperitoneal injection of cisplatin (5 mg/kg). Functional renal indices, enzymatic activities, and morphological variables were studied. One day after the injection, the treated group showed an increase in the magnesium and phosphate fractional urinary excretion (FE) vs the control group (FE Mg = 5.2 +/- SEM 0.5% vs 13.0 +/- 1.7%; P less than 0.01; and FE P = 4.7 +/- 0.7% vs 14.0 +/- 1.9%; P less than 0.01). Two days after cisplatin administration, a decrease in creatinine clearance of treated animals was found, to 0.33 +/- 0.03 vs 0.51 +/- 0.03 ml/min; P less than 0.05. Na-K-ATPase and ouabain-insensitive ATPase activities were studied in the proximal convoluted tubule, the medullary thick ascending limb of the Henle's loop (mTAL), and the distal convoluted tubule. Only in mTAL one day after the cisplatin injection was there a decrease in Na-K-ATPase activity in the treated group vs controls (1103 +/- 145 vs 1734 +/- 189 pmol Pi/mm.h; P less than 0.05). Morphological studies showed a decrease in mTAL diameters on day 1, and an increase in proximal convoluted tuble diameters at day 2 of treated rats vs controls, at 27.8 +/- 0.6 vs 31.4 +/- 0.7 microns; P less than 0.05, and 50.4 +/- 1.2 vs 47.4 +/- 0.2 microns; P less than 0.05 respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases

[Kidney functional reserve. Studies in humans].

The glomerular filtration rate (GF) of each nephron can vary, with increases being caused by stimuli such as nephron reduction and ingestion of proteins. This "functional reserve" (FR), detectable by protein load tests, may be lost in extensive renal destruction where the remaining nephrons are in a permanent state of maximal stimulation. If this hypothesis is true, FR determinations would be of greater value than baseline GFR measurements for evaluating the condition of the remaining parenchyma. A very large number of studies have addressed the FR in normal subjects and have used either diets containing variable amounts of proteins or acute loads given orally (approximately 1 g/kg cooked meat) or intravenously (amino acids). All these studies have evidenced increases in the GFR after the load, regardless of its type, but with major variations across studies and patients. Subjects with a single healthy kidney seem to retain a FR whose magnitude is equal to or smaller than the FR in normal subjects. Conflicting data have been reported in more extensive destruction of the parenchyma, where the FR has been shown to either disappear or persist with no change in percentage. Thus, the practical value of GFR determinations after protein loads has not as yet been established and should be specified using better standardized methods that do not rely on creatinine clearance, at least during oral load tests where serum creatinine levels increases and is no longer stable.

Child

[Evaluation of new markers of bone metabolism in renal osteodystrophy in children].

Serum intact parathormone (PTH 1.84) and osteocalcin levels were evaluated as early markers for secondary hyperparathyroidism in a group of pediatric patient treated with chronic hemodialysis. PTH 1.84 levels which were more closely related with alkaline phosphatase levels than PTH 53.84 levels, allowed to identify a group of children without biologic or roentgenographic evidence of hyperparathyroidism and with a normal residual hormone level. PTH 1.84 levels seem to be a reliable indicator of parathormone secretion than conventional assays and may be used as a routine test for monitoring children under chronic hemodialysis. Conversely, the plasma osteocalcin level measured by radioimmunoassay was increased in all studied patients regardless of parathyroid status and seemed to be of little value for monitoring renal osteodystrophia. Lumbar vertebral plate bone density studies disclosed abnormalities of bone mineralization in half the children with renal failure. Dialyzed or non dialyzed. Patients with decreased bone mineralization presented, in most of cases, a history of previous steroid treatment. A group of children with very severe renal failure had increased bone mineralization. The interpretation of this abnormality remains to be determined.

Bone and Bones

Enalapril does not alter renal function in normotensive, normoalbuminuric, hyperfiltering type 1 (insulin-dependent) diabetic children.

Using a prospective randomised double-blind crossover design, the effect of the angiotensin converting enzyme inhibitor enalapril compared to a placebo was studied in 18 normotensive, normoalbuminuric Type 1 (insulin-dependent) diabetic children. Each patient had a high normal or clearly elevated glomerular filtration rate (145 ml.min-1.1.73 m2 or higher) in the 6 months prior to the study. Enalapril, 0.5 mg.kg-1.day-1, was given for 4 weeks followed by placebo for 4 weeks, or vice versa. At the end of each period, glomerular filtration rate, renal plasma flow, blood pressure, plasma renin activity, and converting enzyme activity were determined. Enalapril caused significant reduction (p = less than 0.001) in blood pressure and converting enzyme activity and a rise in plasma renin activity. A slight but not significant rise in glomerular filtration rate and renal plasma flow without change in filtration fraction was observed. These data suggest that the renin angiotensin system is not involved in the glomerular hyperfiltration of Type 1 diabetes, and can be interpreted as showing no evidence for the presence of intraglomerular hypertension in these patients.

Adolescent

Comparison of plasma renin and prorenin in healthy infants and children as determined with an enzymatic method and a new direct immunoradiometric assay.

We compared plasma active and inactive renin (prorenin) concentrations and activities in infants and children, as measured with a newly available direct immunoradiometric assay kit for active renin and a widely used enzymatic renin assay (plasma renin activity). The study was performed in 57 healthy infants and children under steady-state conditions and in eight subjects after orthostatic stimulation. Our study; (i) reports concentrations for active and inactive renin determined by the immunoradiometric assay in normal infants and children; (ii) confirms, by use of the immunoradiometric assay, the previously described decrease in plasma active and inactive renin, as measured by the enzymatic assay, with increasing age; and (iii) shows close correlations between the results obtained by immunoradiometric and enzymatic assays for active and inactive renin in normal infants and children.

Adolescent