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M Dechaux

Publications and source records attributed to M Dechaux.

At least 19 recordsLinked to original sources
PubMed2001

Paracellin-1 is critical for magnesium and calcium reabsorption in the human thick ascending limb of Henle.

BACKGROUND: A new protein, named paracellin 1 (PCLN-1), expressed in human thick ascending limb (TAL) tight junctions, possibly plays a critical role in the control of magnesium and calcium reabsorption, since mutations of PCLN-1 are present in the hypomagnesemia hypercalciuria syndrome (HHS). However, no functional experiments have demonstrated that TAL magnesium and calcium reabsorption were actually impaired in patients with HHS. METHODS: Genetic studies were performed in the kindred of two unrelated patients with HHS. Renal magnesium and calcium reabsorption in TAL were analyzed in one homozygous affected patient of each family, one patient with extrarenal hypomagnesemia (ERH), and two control subjects (CSs). RESULTS: We found two yet undescribed mutations of PCLN-1 (Gly 162 Val, Ala 139 Val). In patients with HHS, renal magnesium and calcium reabsorptions were impaired as expected; NaCl renal conservation during NaCl deprivation and NaCl tubular reabsorption in diluting segment were intact. Furosemide infusion in CS markedly increased NaCl, Mg, and Ca urinary excretion rates. In HHS patients, furosemide similarly increased NaCl excretion, but failed to increase Mg and Ca excretion. Acute MgCl(2) infusion in CS and ERH patient provoked a dramatic increase in urinary calcium excretion without change in NaCl excretion. When combined with MgCl(2) infusion, furosemide infusion remained able to induce normal natriuretic response, but was unable to increase urinary magnesium and calcium excretion further. In HHS patients, calciuric response to MgCl(2) infusion was blunted. CONCLUSION: This study is the first to our knowledge to demonstrate that homozygous mutations of PCLN-1 result in a selective defect in paracellular Mg and Ca reabsorption in the TAL, with intact NaCl reabsorption ability at this site. In addition, the study supports a selective physiological effect of basolateral Mg(2+) and Ca(2+) concentration on TAL divalent cation paracellular permeability, that is, PCLN-1 activity.

Adolescent↗
PubMed2001

Hereditary hypophosphatemic rickets with hypercalciuria: report of a new kindred.

We report a new kindred of hereditary hypophosphatemic rickets with hypercalciuria. The symptomatic child and several relatives had increased renal phosphate clearance leading to hypophosphatemia, hyperabsorptive hypercalciuria, low PTH and increased 1,25-(OH)2D serum level. However, association with vitamin D deficiency and normal urinary excretion of cyclic AMP might suggest another tubular defect in phosphate transport.

Calcium↗
PubMed1997

Subtotal nephrectomy alters tubular function: effect of phosphorus restriction.

Few studies have examined tubular function after subtotal nephrectomy (Nx) and conservative treatments. The effects of 70% and 80% Nx (associated with dietary phosphate restriction in the latter case) on the apical brush border membrane (BBM) enzymes 5'-nucleotidase, gamma glutamyl-transferase and alkaline-phosphatase, and one BBM Na-phosphate cotransporter (NaPi-2) were studied in rats after a six week period. Changes in activity and mRNA abundance of the BBM enzymes and in NaPi-2 protein and mRNA abundance were compared with changes in the distal markers of Na,K-ATPase activity and epidermal growth factor (EGF) production. The activity, but not the mRNA of BBM enzymes, was moderately reduced by the 70% Nx. Both the mRNA and activity of gamma glutamyl-transferase and alkaline-phosphatase were decreased in the 80% Nx, and the NaPi-2 mRNA, protein and Na,K-ATPase activities were also reduced. These effects (except for 5'nucleotidase and Na,K-ATPase) were partly reversed by phosphate restriction. Overproduction of EGF occurred after the 70% Nx, was blunted in the 80% Nx, and then partially restored by phosphate restriction. Aggravation of tubular alteration was associated with enhanced renal hyperplasia (increased DNA mass), reduced GFR and hyperphosphatemia, and high PTH levels, but reduced cAMP excretion. Improvement following phosphate restriction was associated with reduced hyperplasia and lowering of phosphatemia and PTH levels. These data demonstrate that Nx selectively affected BBM function through transcriptional changes that were partially reversed by phosphate restriction. Regulatory factors involved in these changes may include intracellular phosphate content and growth factors, but not the PTH effects that are impaired in chronic renal failure.

5'-Nucleotidase↗
PubMed1996

Decrease in endothelin-1 renal receptors during the 1st month of life in the rat.

Endothelin-1 (Et1), like angiotensin II, is implicated in postnatal maturation and development. The present study was designed to identify Et1 receptors and subtype Et1 receptors present in rat kidney between 1 and 30 days of postnatal life. On day 1, high-affinity and high-density Et1 binding sites were identified in rat kidney. The dissociation constant and maximum binding for ET1 to membranes from whole kidney were 0.073 +/- 0.05 nM and 1,345.9 +/- 73 fmol/mg protein, respectively. On day 30, affinity and receptor density were markedly decreased. The dissociation constant and maximum binding were 0.147 +/- 0.021 nM (P < 0.01) and 633.2 +/- 56.4 fmol/mg protein (P < 0.001), respectively. Using BQ 123 (EtA-selective antagonist) and sarafotoxin S6c (EtB-selective agonist), the two Et1 receptor subtypes EtA and EtB were identified in 1- and 30-day-old rat kidney. BQ 123 selectively recognized EtA receptors with high affinity (2.9 +/- 0.44 on day 1 and 4.0 +/- 0.5 nM on day 30) and sarafotoxin S6c bound with higher affinity EtB receptors (0.871 +/- 0.14 on day 1 and 0.717 +/- 0.12 nM on day 30). Between birth and day 30, the EtA binding capacity was decreased (304 +/- 27 vs. 752 +/- 202 fmol/mg protein, P < 0.05), whereas EtB binding was not affected (514 +/- 87 vs. 656 +/- 171 fmol/mg protein, NS). The decrease in the total number of Et1 receptors during the 1st month of life may be due to the concomitant decrease in the number of EtA receptors. Increased Et1 receptor density in early postnatal life suggests an influence of Et1 on immature kidney circulation and/or kidney growth.

Animals↗
PubMed1996

Acidosis prevents growth hormone-induced growth in experimental uremia.

The effects of 2 weeks of a daily injection (2 IU/day) of recombinant human growth hormone (GH) were studied in young (60-g) growing rats in two experiments. Experiment 1 was performed in uremic animals (mean plasma creatinine 65-71 mumol/l) who were either acidotic (mean bicarbonate 11.5 mmol/l) or had acidosis corrected (mean bicarbonate 26 mmol/l) by addition of sodium bicarbonate to the diet. Experiment 2 used rats with normal renal function (plasma creatinine 25 mumol/l) who were either non-acidotic but restricted to the dietary intake of uremic rats or rendered acidotic by ammonium chloride. GH induced an increase in body weight and length in non-acidotic uremic (+33% and +41%) and in non-acidotic food-restricted (+13% and +42%) rats, associated with an increased rate of protein synthesis and little change in plasma insulin-like growth factor 1 (IGF 1). In both acidotic rat groups, GH altered none of the parameters studied. Thus: (1) the presence of severe metabolic acidosis blunts the response to GH in uremic and non-uremic rats and (2) the increment of growth rate does not depend on a rise in plasma IGF 1.

Acidosis↗
PubMed1996

Growth hormone action is blunted by acidosis in experimental uremia or acid load.

The effects of rhGH (H) daily injection (2 IU/d) and of vehicle (V) during two weeks were studied in young (60 g) growing rats. Experiment I was performed in uremic rats (mean plasma creatinine: 65-71 mumol/l) either acidotic (mean HCO3-:11.5 mmol/l: UAH, n = 20; UAV, n = 18), or with corrected acidosis by addition of NaHCO3 in the diet (mean HCO3-:26 mmol/l: UBH, n = 25; UBV, n = 23). Experiment II used rats with normal renal function (plasma creatinine: 25 mumol/l), either non-acidotic but food restricted to the dietary intake of uremic rats (CRH: n = 18, CRV: n = 18), or rendered acidotic by NH4Cl (CAH: n = 16, CAV: n = 16). GH induced an augmentation of body weight and length gains in non-acidotic uremic rats (+33% and +41%: p < 0.01), and in non-acidotic food restricted rats (+13% and 42%: p < 0.05 and p < 0.0001). This was associated with increased protein synthesis rate in muscle and with little change of food intake as well as of plasma IGF 1. Plasma IGF 1 kept the same relationship to food intake, regardless of treatment, but length gain for each level of plasma IGF 1 was enhanced by GH in GH responding groups. In both acidotic rat groups, GH altered none of the parameters studied. Thus: 1) the presence of severe metabolic acidosis blunts the response to GH in uremic and non-uremic rats. 2) The increment of growth rate does not depend on a rise of plasma IGF 1.

Acidosis↗
PubMed1994

In vivo unaltered muscle protein synthesis in experimental chronic metabolic acidosis.

Chronic metabolic acidosis (CMA) is a major cause of growth defect, implying disturbances of protein metabolism. Previously, in vivo studies performed in the fasting state showed enhanced whole body protein turnover, whereas in vitro studies showed unchanged muscle protein synthesis. The present study is the first to determine the effects of CMA on muscle protein synthesis and degradation in vivo. Two studies were performed in 60 g male rats fed a 30% casein diet. In study I, one group was sham-operated (C rats), and two groups underwent subtotal nephrectomy. One of them developed acidosis (UA rats) which was corrected in the other by NaHCO3 in the diet (UNA rats). Study II compared sham-operated rats rendered acidotic by NH4Cl in the drinking water (CA rats) and normal pair-fed (CNA) rats. Fractional protein synthesis rate (FSR) was determined in gastrocnemius muscle after injection of 3H-phenylalanine. Fractional protein degradation rate (FDR) was calculated as FSR minus fractional rate of muscle growth (FGR). In study I, UA rats had lower growth and N balance (163 +/- 12 vs. 216 +/- 11 mg N/day; P < 0.001) than UNA rats, despite identical food intake (11 g/day). This was associated with identical FSR (10.4 +/- 0.5 vs. 10.9 +/- 0.5%/day), but enhanced protein degradation (6.30 +/- 0.99 vs. 5.10 +/- 0.71%/day; P < 0.05). Plasma insulin, C peptide, PTH and corticosterone did not differ in UA and UNA rats, whereas plasma IGF-I was markedly reduced (147 +/- 21 vs. 283 +/- 27 ng/ml; P < 0.01) in UA rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗
PubMed1993

[Antenatal form of Bartter's syndrome].

Six cases of tubular disorder of antenatal onset responsible for biological manifestations characteristic of Bartter syndrome and severe hypercalciuria are reported. In all six cases, severe hydramnios occurred during pregnancy between the 26th and 28th week after the last menstrual period. All six patients were born prematurely; gestational age ranged from 20 to 35 weeks. Major polyuria with dehydration occurred immediately after birth. The amounts of water and sodium needed to compensate urinary losses ranged from 280 to 370 ml/kg/day and 25 to 43 mmol/kg/d, respectively, during the first two postnatal months. Decreased serum potassium levels and increased plasma levels of renin and aldosterone were seen in all six patients. Increased urinary excretion of calcium was evidenced during the first postnatal week in three cases. Urinary calcium excretion in the six patients ranged from 15 to 30 mg/kg/d. Nephrocalcinosis developed in all six patients and two patients developed urinary lithiasis. One patient died at one month of age from necrotizing enteropathy. The five remaining patients gradually developed severe growth failure with measurements between 4 and 5.5 SDs below the mean. These five patients had evidence of hyperparathyroidism including increased serum levels of parathyroid hormone (5/5), increased serum alkaline phosphatase activity (4/5), and roentgenographic bone changes (1/5). Ionized calcium assays performed in three of the five patients disclosed low values (range 1.25-1.47 mmol/l; mean = 1.35; normal values = 1.42-1.62), although total serum calcium levels were normal or high (range 2.16-2.98 mmol/l; mean 2.61; normal values = 2.45-2.65) probably as a result of chronic dehydration.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗