A five-year-old boy is presented to Necker hospital for a dilated hypertrophic cardiomyopathy. Th... more A five-year-old boy is presented to Necker hospital for a dilated hypertrophic cardiomyopathy. The implantation of the Berlin Heart Excor(®) ventricular assist device was performed. This pediatric-sized Berlin Heart(®) device provides mechanical support for young infants and children of all ages to sustain the failing cardiac circulation over several months, until either recovery of myocardial function or heart transplantation. It remains difficult to identify patients with sufficient recovery and the right time for explantation of the Berlin Heart(®). Currently, the decision as to whether a patient should be weaned from the system is mainly based on echocardiographic data. Humoral biomarker, associated to echocardiographic features, would be helpful to identify children who might recover without heart transplantation. We observed that our young patient presented highly elevated BNP plasma levels before mechanical support, and a significant decrease during Berlin Heart(®) support. M...
We assessed oxidative stress in 35 chronic renal failure under conservative treatment (CRF), 50 h... more We assessed oxidative stress in 35 chronic renal failure under conservative treatment (CRF), 50 hemodialysed (HD) and 30 renal transplant (RT) patients, and 31 age- and sex-matched healthy subjects. Compared to controls, CRF patients exhibited significantly higher conjugated dienes (139 +/- 37 versus 121 +/- 22 micromol/l) and LDL oxidation (126 +/- 65 versus 99 +/- 46 micromol/l). Glutathione peroxidase activity was decreased in CRF and HD (5.31 +/- 2.46 and 5.39 +/- 2.32 versus 7.42 +/- 2.72 U/ml in healthy subjects). Superoxide dismutase activity was lower in HD (91 +/- 38 U/ml) and higher in RT patients (132 +/- 33 U/ml) than controls (116 +/- 30 U/ml). Plasma zinc concentrations were significantly decreased in CRF and HD patients and copper concentrations were significantly decreased in TPR. Plasma selenium levels were normal in the three groups of patients. Vitamin A was significantly increased, whereas vitamin E was normal in the 3 groups of patients compared to healthy contr...
Sodium is an important determinant of urinary calcium excretion, and race is an important determi... more Sodium is an important determinant of urinary calcium excretion, and race is an important determinant of calcium retention. The effect of dietary sodium on calcium retention and the influence of race have not been studied in adolescence, the life stage during which peak bone mass is accrued. The study reported here was undertaken to compare racial differences in calcium retention as a function of dietary salt intake. A total of 35 adolescent girls (22 black and 13 white) participated in two 20-d metabolic summer camps, separated by 2 wk, that simulated a free-living environment. The effect of changes in dietary sodium on calcium retention was tested in a randomized-order, crossover design with 2 concentrations of sodium-1.30 g/d (57 mmol/d) and 3.86 g/d (168 mmol/d)-and a constant calcium intake of 815 mg/d (20 mmol/d). Both race and sodium intake significantly affected calcium retention (P < 0.01). Calcium retention was significantly greater in black girls than in white girls, r...
The main component of urinary calculi in industrialized countries is calcium oxalate. Its detecti... more The main component of urinary calculi in industrialized countries is calcium oxalate. Its detection in stones is easily performed by infrared spectrophotometry. However its two crystalline forms calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD), which are linked to different aetiologies, provide similar patterns, with overlapping vibrations leading to difficulties in differentiation and quantitation of both the phases in mixtures. Some minor but characteristic bands of each crystalline species are emphasized for analytical purposes. The method of zero-crossing-point first-derivative spectrophotometry was applied to calcium oxalate species quantitation and revealed to be easy, accurate, precise and very well adapted to routine laboratories.
Background: Atherosclerosis and vascular calcification are major contributors to cardiovascular m... more Background: Atherosclerosis and vascular calcification are major contributors to cardiovascular morbidity and mortality among chronic kidney disease patients. The mevalonate pathway may play a role in this vascular pathology. Farnesyltransferase inhibitors such as R115777 block one branch of mevalonate pathway. We studied the effects of farnesyltransferase inhibitor R115777 on vascular disease in apolipoprotein E deficient mice with chronic renal failure and on mineral deposition in vitro. Methods and results: Female uremic and non-uremic apolipoprotein E deficient mice were randomly assigned to four groups and treated with either farnesyltransferase inhibitor R115777 or vehicle. Farnesyltransferase inhibitor R115777 inhibited protein prenylation in mice with chronic renal failure. It decreased aortic atheromatous lesion area and calcification in these animals, and reduced vascular nitrotyrosine expression and total collagen as well as collagen type I content. Proteomic analysis revealed that farnesyltransferase inhibitor corrected the chronic renal failure-associated increase in serum apolipoprotein IV and a globin, and the chronic renal failure-associated decrease in serum fetuin A. Farnesyltransferase inhibitor further inhibited type I collagen synthesis and reduced mineral deposition in vascular smooth muscle cells in vitro, probably involving Ras-Raf pathway. Conclusions: We show for the first time that farnesyltransferase inhibition slows vascular disease progression in chronic renal failure by both indirect systemic and direct local actions. This beneficial effect was mediated via a reduction in oxidative stress and favorable changes in vasoprotective peptides.
Resume Cette revue fait une synthese des connaissances actuelles sur l’insuffisance renale aigue ... more Resume Cette revue fait une synthese des connaissances actuelles sur l’insuffisance renale aigue (IRA), en commencant par un rappel des differentes etiologies possibles et du diagnostic biologique differentiel entre IRA fonctionnelle et organique. Elle met en avant l’importance d’etablir une classification des IRA en fonction de la gravite, en tenant compte a la fois des variations des concentrations de creatininemie et de production d’urine. Elle souligne egalement l’emergence de nouveaux bio-marqueurs tres interessants comme la NGAL (neutrophil-gelatinase associated lipocalin) pour etablir un diagnostic precoce d’IRA avant l’augmentation de la creatinine serique, meme si la place de ces bio-marqueurs reste actuellement reservee a la prise en charge de certains patients a haut risque. Enfin, elle fait le point sur la necessite d’evaluer la fonction renale dans les 2 mois qui suivent tout episode d’IRA chez tous les patients, afin de pouvoir detecter ceux qui ont recupere en totalite et ceux qui debutent ou aggravent une maladie renale chronique, afin de pouvoir les prendre en charge selon les recommandations de bonnes pratiques cliniques.
Transplant vasculopathy may be considered as an accelerated form of atherosclerosis resulting in ... more Transplant vasculopathy may be considered as an accelerated form of atherosclerosis resulting in chronic rejection of vascularized allografts. After organ transplantation, a diffuse intimal thickening is observed, leading to the development of an atherosclerosis plaque due to a significant monocyte infiltration. This results from a chronic inflammatory process induced by the immune response. In this study, we investigated the impact of two immunosuppressive drugs used in therapy initiated after organ transplantation, mycophenolate mofetil, and rapamycin, on the apoptotic response of monocytes induced or not by oxidized LDL. Here we show the pro-apoptotic effect of these two drugs through two distinct signaling pathways and we highlight a synergistic effect of rapamycin on apoptosis induced by oxidized LDL. In conclusion, since immunosuppressive therapy using mycophenolate mofetil or rapamycin can increase the cell death in a monocyte cell line, this treatment could exert similar eff...
1. The effect of silicon (Si) contained in drinking water and solid food on the intestinal absorp... more 1. The effect of silicon (Si) contained in drinking water and solid food on the intestinal absorption of aluminium (Al) remains a matter of debate. The present study was designed to readdress this issue in the experimental animal, and to examine concomitantly the effects of citrate and the fasting state, respectively. 2. Three groups of young, non-fasted rats (n = 8 per group) were gavaged by solutions containing 3.8 ng of 26Al, 63 ng of 27Al, and either distilled water (< 0.1 mg/l Si) or commercial mineral water with a medium (6 mg/l) or high (14 mg/l) Si concentration. 3. Two other groups of eight non-fasted rats each received the same distilled water or high-Si gavage solution, respectively, together with a high citrate concentration (62 g/l). In each case the animals had free access to drinking water for 5 days before and 2 days after the gavage, containing the same Si concentration as in the gavage solution. A sixth group of eight rats was gavaged by low-Si, Al and distilled...
Vitamin status and role in end stage renal disease (ESRD) is controversial. This study was aimed ... more Vitamin status and role in end stage renal disease (ESRD) is controversial. This study was aimed at assessing vitamin A, E, B12, and folic acid status in Tunisian ESRD patients and testing their predictive value for overall mortality and cardiovascular events (CVE). We examined plasma vitamin A, E, B12, and folic acid in 115 ESRD patients and looked for any correlation with all-cause mortality and CVE after a six year follow-up. Vitamin A and E were determined by HPLC and vitamin B12 and folic acid were determined by enzyme immunoassay. At enrolment, plasma vitamin A was higher in patients than controls, while plasma vitamin B12 was higher in HD patients. No significant differences were observed for plasma vitamin E and folic acid concentrations between patients and controls. Folic acid and vitamin B12 levels were higher in supplemented patients. During the follow-up period, 17 patients were lost, 15 died, and 36 presented a CVE. Survival analysis showed that mortality and/or CVE tr...
As part of a tender AP-HP Paris Hospitals, an assessment of the reliability record of five blood ... more As part of a tender AP-HP Paris Hospitals, an assessment of the reliability record of five blood glucose monitoring systems (BGMSs) (Optium Xceed (Abbott), Contour TS (Bayer), One Touch Ultra (Lifescan), Stat Strip Xpress (Nova) and Accu Check (Roche) and an evaluation of their sensitivity to changes in hematocrit were conducted in 4 hospitals of Paris. In terms of inaccuracy, all BGMSs have submitted CV repetability under the limits of acceptability. One BGMS (Lifescan) presented a CV of reproducibility outside limit of acceptability (13.1%). The inaccuracy was measured by a comparison method on multiparameter analyser relative to the hexokinase method for two sites, the glucose oxidase for the two others. The coefficients of correlation varied from 0.8405 to 0.9303. However, according to both defined acceptability criteria (absolute value difference between the result acquired on analyzer and those determined with the BGMS), the percentage of results outside acceptability was abov...
This study was aimed to determine the prevalence of several classical and non-classical cardiovas... more This study was aimed to determine the prevalence of several classical and non-classical cardiovascular risk factors, and to test their association with cardiovascular events in Tunisian patients with end-stage renal disease. A total of 35 chronic renal failure, 50 hemodialysed and 30 renal transplant recipient patients and 31 healthy subjects were included. Hypertension, elevated plasma concentrations of total homocysteine, fibrinogen, C-reactive protein, and lipoprotein(a) were highly prevalent in patients, whereas, smoking, hypertriglyceridemia, hypercholesterolemia, hypoHDLemia, and hypoalbuminemia were less common. In univariate analysis, cardiovascular events were associated with age, hypertension, and the top quartile of the total homocysteine and C-reactive protein values. When controlling for several potential confounding factors, cardiovascular events remained associated with age, hypertension (OR, 7.07; 95% CI, 1.76-28.34; P=0.01), and the top quartile of total homocystein...
Progrès en urologie : journal de l'Association française d'urologie et de la Société française d'urologie, 2003
More than ten per cent of stones are associated with a urinary tract abnormality. To verify wheth... more More than ten per cent of stones are associated with a urinary tract abnormality. To verify whether the malformation influences stone composition, we studied the composition of stones observed in fifteen urological abnormalities. This study is based on 1,461 stones associated with a clearly defined malformation analysed by infrared spectroscopy plus 402 bladder stones in men with benign prostatic hyperplasia. In this series of 1,863 abnormalities, 732 (39.3%) involved the kidney, 561 (30.1%) involved the ureter and 570 (30.6%) involved the lower tract. Whewellite stones were predominant in all renal abnormalities with the exception of cysts, which were mainly associated with uric acid. The main differences concerned the second constituent: weddellite in horseshoe kidneys, carbapatite in Cacchi-Ricci disease and caliceal abnormalities. Struvite was uncommon (<10%). Whewellite was the main component in ureteric abnormalities except for megaureter and reflux in which carbapatite was...
Progrès en urologie : journal de l'Association française d'urologie et de la Société française d'urologie, 2001
High urine volume is known to be an effective measure for preventing stone recurrence. However, o... more High urine volume is known to be an effective measure for preventing stone recurrence. However, only few studies have investigated its effects on crystalluria and spontaneous passage of calculi. The aim of the study was to assess the effects of high diuresis on stone expulsion and recurrence. 219 patients were consulting for a first stone episode in Urology units in the Mostaganem area between September 1996 and December 1999. All stones were under 6 mm in size. The patients were divided in two groups: group I included 129 patients (68 males, 61 females) who agreed to be on a high water intake, at least 3 liters per day, over a two months period and to be followed periodically by crystalluria examination in the first morning urine; group II included 90 patients (63 males, 27 females) who declined diuresis advice and urine collection for crystalluria examination. First morning urine collected in patients of group I were examined before (2.95 voidings per subject) and while on diuresi...
1. To determine whether treatment with octreotide, a somatostatin analogue, may diminish or preve... more 1. To determine whether treatment with octreotide, a somatostatin analogue, may diminish or prevent long-term diabetic renal hypertrophy and nephropathy, uninephrectomized streptozotocin-diabetic rats maintained under moderate glycaemic control (approximately 300 mg/dl) were treated with either placebo (n = 10 rat/group) or octreotide for 14 weeks. Uninephrectomized non-diabetic rats given either placebo or octreotide served as controls. 2. Average body weight was diminished and kidney weight, daily urinary protein excretion, glomerular filtration rate and renal plasma flow were elevated in both diabetic groups relative to controls. 3. Administration of octreotide reduced average body weight and packed cell volume in non-diabetic and diabetic rats compared with their respective controls, but did not affect glomerular hyperfiltration or the increase in urinary protein excretion. 4. Histological examination at 14 weeks disclosed unequivocal glomerular hypertrophy and mild glomerular a...
Intestinal calcium absorption has been shown to include two processes, a saturable transcellular ... more Intestinal calcium absorption has been shown to include two processes, a saturable transcellular movement and a non-saturable paracellular pathway. The potential utility of cell monolayers for studying transepithelial intestinal calcium transport has already been demonstrated; however, simultaneous evaluation of the contribution of the saturable transcellular and of the non-saturable paracellular processes to the total transepithelial transport has not yet been attempted. The aim of this study was to investigate the contribution both of transcellular and paracellular transport processes to the total transepithelial calcium transport in two cell culture monolayers. Caco-2 cells and a clone derived from HT-29 cells (HT29-Cl.19A), two cell lines derived from colon adenocarcinomas which are known to be able to exhibit typical enterocytic differentiation, were used. Cell monolayers were grown on a permeable support and used after 15 days of culture when these cells express enterocytic differentiation and high transepithelial resistance. Isotopic transport rate measurements were performed in the absence of a chemical gradient. The paracellular route was evaluated using [ 3 H]mannitol. Calcium and [ 3 H]mannitol transport rates across cell monolayers were not significantly different. Augmentation of calcium uptake by 200 mM sorbitol did not significantly increase calcium or mannitol transepithelial transport; however, calcium accumulation in the cells was increased by about 200%. Modulation of the monolayer permeability by addition of 10 nM vasoactive intestinal polypeptide (VIP) or 0.5 mM carbachol treatment, which respectively increased and decreased the transepithelial resistance, consequently modified calcium and mannitol transport in a parallel manner. Our results show that Caco-2 and HT29-Cl.19A cell monolayers are good models for studying the calcium paracellular transport pathway. & k w d : Key words Transepithelial calcium transport • Caco-2 • HT-29 • Paracellular pathway& b d y :
France and director at INSERM. In addition to fundamental research studies in her career on hepat... more France and director at INSERM. In addition to fundamental research studies in her career on hepatitis B and Crelated liver carcinogenesis and calcium signalling, she has focused on applied research, targeting the domains of predictive oncology and prenatal diagnosis; her research activity led to the discovery and development of ISET (isolation by size of epithelial tumour/trophoblastic cells) for the characterization of circulating tumour and trophoblastic cells, thus permitting non-invasive cancer diagnostics and non-invasive prenatal diagnosis and leading to high-level publications and numerous awards.
Platelet cytosolic free calcium concentration ([Ca2+]i) and intracellular pH (pH i) (including th... more Platelet cytosolic free calcium concentration ([Ca2+]i) and intracellular pH (pH i) (including their responses to thrombin), as well as erythrocyte [Ca2+]i and 45Ca2+ influx, were studied in Lyon hypertensive (LH) and normotensive (LN) rats aged 3 months. Platelets of LH rats were characterized by substantially elevated basal [Ca2+]i values, higher [Ca2+]i levels after thrombin stimulation, and enhanced initial rate of thrombin-induced Mn 2+ entry through receptor-operated Ca 2+ channels. Basal platelet pH i values were not significantly different in LH and LN animals but thrombin elicited a significant alkalinization only in LH platelets. Erythrocytes of LH rats had an enhanced initial rate of 45Ca2+ and tended to elevated [Ca2+]i levels. Our data indicate profound alterations in cell Ca 2+ handling in platelets and erythrocytes of LH rats, similar to those previously described in spontaneously hypertensive rats of the Okamoto-Aoki strain. The analysis of the relations between blood pressure, plasma lipids, and cell Ca 2+ handling suggested that triglycerides, but not cholesterol, might be involved in altered platelet Ca 2+ handling in LH rats.
Carnitine deficiency has recently been incriminated in the pathogenesis of the disturbed lipid me... more Carnitine deficiency has recently been incriminated in the pathogenesis of the disturbed lipid metabolism observed in hemodialysis patients. The present study was performed to investigate the effects of L-carnitine administration on the lipid metabolism of rats with experimental chronic renal failure as compared to normal rats. Three groups of rats were studied: the first had induced chronic uremia, the second was sham-operated and pair-fed with the first, and the third was sham-operated and fed ad libitum. Serum triglycerides were significantly higher in uremic rats than in control animals of both groups. In addition to triglycerides, serum total cholesterol and phospholipids were also increased in uremic rats. The fractional clearance rate of Intralipid [K2(%)] was decreased in uremic as compared to control animals. The in vivo oxidation of radiolabeled palmitate was lower in uremic than in ad libitum-fed control animals but not lower than in pair-fed control rats. The daily oral administration of L-carnitine to uremic rats was associated with stable serum triglycerides. On the contrary, serum triglycerides increased significantly in the untreated uremic rats over the same period of time. Serum total cholesterol and phospholipids remained similar in the presence and the absence of L-carnitine treatment. The intravenous fat tolerance test of carnitine-supplemented uremic rats improved slightly, although not significantly, when compared to that of untreated uremic rats. In conclusion, oral L-carnitine supplementation in chronically uremic rats had only modest or no effects on several plasma lipid parameters.(ABSTRACT TRUNCATED AT 250 WORDS)
A five-year-old boy is presented to Necker hospital for a dilated hypertrophic cardiomyopathy. Th... more A five-year-old boy is presented to Necker hospital for a dilated hypertrophic cardiomyopathy. The implantation of the Berlin Heart Excor(®) ventricular assist device was performed. This pediatric-sized Berlin Heart(®) device provides mechanical support for young infants and children of all ages to sustain the failing cardiac circulation over several months, until either recovery of myocardial function or heart transplantation. It remains difficult to identify patients with sufficient recovery and the right time for explantation of the Berlin Heart(®). Currently, the decision as to whether a patient should be weaned from the system is mainly based on echocardiographic data. Humoral biomarker, associated to echocardiographic features, would be helpful to identify children who might recover without heart transplantation. We observed that our young patient presented highly elevated BNP plasma levels before mechanical support, and a significant decrease during Berlin Heart(®) support. M...
We assessed oxidative stress in 35 chronic renal failure under conservative treatment (CRF), 50 h... more We assessed oxidative stress in 35 chronic renal failure under conservative treatment (CRF), 50 hemodialysed (HD) and 30 renal transplant (RT) patients, and 31 age- and sex-matched healthy subjects. Compared to controls, CRF patients exhibited significantly higher conjugated dienes (139 +/- 37 versus 121 +/- 22 micromol/l) and LDL oxidation (126 +/- 65 versus 99 +/- 46 micromol/l). Glutathione peroxidase activity was decreased in CRF and HD (5.31 +/- 2.46 and 5.39 +/- 2.32 versus 7.42 +/- 2.72 U/ml in healthy subjects). Superoxide dismutase activity was lower in HD (91 +/- 38 U/ml) and higher in RT patients (132 +/- 33 U/ml) than controls (116 +/- 30 U/ml). Plasma zinc concentrations were significantly decreased in CRF and HD patients and copper concentrations were significantly decreased in TPR. Plasma selenium levels were normal in the three groups of patients. Vitamin A was significantly increased, whereas vitamin E was normal in the 3 groups of patients compared to healthy contr...
Sodium is an important determinant of urinary calcium excretion, and race is an important determi... more Sodium is an important determinant of urinary calcium excretion, and race is an important determinant of calcium retention. The effect of dietary sodium on calcium retention and the influence of race have not been studied in adolescence, the life stage during which peak bone mass is accrued. The study reported here was undertaken to compare racial differences in calcium retention as a function of dietary salt intake. A total of 35 adolescent girls (22 black and 13 white) participated in two 20-d metabolic summer camps, separated by 2 wk, that simulated a free-living environment. The effect of changes in dietary sodium on calcium retention was tested in a randomized-order, crossover design with 2 concentrations of sodium-1.30 g/d (57 mmol/d) and 3.86 g/d (168 mmol/d)-and a constant calcium intake of 815 mg/d (20 mmol/d). Both race and sodium intake significantly affected calcium retention (P < 0.01). Calcium retention was significantly greater in black girls than in white girls, r...
The main component of urinary calculi in industrialized countries is calcium oxalate. Its detecti... more The main component of urinary calculi in industrialized countries is calcium oxalate. Its detection in stones is easily performed by infrared spectrophotometry. However its two crystalline forms calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD), which are linked to different aetiologies, provide similar patterns, with overlapping vibrations leading to difficulties in differentiation and quantitation of both the phases in mixtures. Some minor but characteristic bands of each crystalline species are emphasized for analytical purposes. The method of zero-crossing-point first-derivative spectrophotometry was applied to calcium oxalate species quantitation and revealed to be easy, accurate, precise and very well adapted to routine laboratories.
Background: Atherosclerosis and vascular calcification are major contributors to cardiovascular m... more Background: Atherosclerosis and vascular calcification are major contributors to cardiovascular morbidity and mortality among chronic kidney disease patients. The mevalonate pathway may play a role in this vascular pathology. Farnesyltransferase inhibitors such as R115777 block one branch of mevalonate pathway. We studied the effects of farnesyltransferase inhibitor R115777 on vascular disease in apolipoprotein E deficient mice with chronic renal failure and on mineral deposition in vitro. Methods and results: Female uremic and non-uremic apolipoprotein E deficient mice were randomly assigned to four groups and treated with either farnesyltransferase inhibitor R115777 or vehicle. Farnesyltransferase inhibitor R115777 inhibited protein prenylation in mice with chronic renal failure. It decreased aortic atheromatous lesion area and calcification in these animals, and reduced vascular nitrotyrosine expression and total collagen as well as collagen type I content. Proteomic analysis revealed that farnesyltransferase inhibitor corrected the chronic renal failure-associated increase in serum apolipoprotein IV and a globin, and the chronic renal failure-associated decrease in serum fetuin A. Farnesyltransferase inhibitor further inhibited type I collagen synthesis and reduced mineral deposition in vascular smooth muscle cells in vitro, probably involving Ras-Raf pathway. Conclusions: We show for the first time that farnesyltransferase inhibition slows vascular disease progression in chronic renal failure by both indirect systemic and direct local actions. This beneficial effect was mediated via a reduction in oxidative stress and favorable changes in vasoprotective peptides.
Resume Cette revue fait une synthese des connaissances actuelles sur l’insuffisance renale aigue ... more Resume Cette revue fait une synthese des connaissances actuelles sur l’insuffisance renale aigue (IRA), en commencant par un rappel des differentes etiologies possibles et du diagnostic biologique differentiel entre IRA fonctionnelle et organique. Elle met en avant l’importance d’etablir une classification des IRA en fonction de la gravite, en tenant compte a la fois des variations des concentrations de creatininemie et de production d’urine. Elle souligne egalement l’emergence de nouveaux bio-marqueurs tres interessants comme la NGAL (neutrophil-gelatinase associated lipocalin) pour etablir un diagnostic precoce d’IRA avant l’augmentation de la creatinine serique, meme si la place de ces bio-marqueurs reste actuellement reservee a la prise en charge de certains patients a haut risque. Enfin, elle fait le point sur la necessite d’evaluer la fonction renale dans les 2 mois qui suivent tout episode d’IRA chez tous les patients, afin de pouvoir detecter ceux qui ont recupere en totalite et ceux qui debutent ou aggravent une maladie renale chronique, afin de pouvoir les prendre en charge selon les recommandations de bonnes pratiques cliniques.
Transplant vasculopathy may be considered as an accelerated form of atherosclerosis resulting in ... more Transplant vasculopathy may be considered as an accelerated form of atherosclerosis resulting in chronic rejection of vascularized allografts. After organ transplantation, a diffuse intimal thickening is observed, leading to the development of an atherosclerosis plaque due to a significant monocyte infiltration. This results from a chronic inflammatory process induced by the immune response. In this study, we investigated the impact of two immunosuppressive drugs used in therapy initiated after organ transplantation, mycophenolate mofetil, and rapamycin, on the apoptotic response of monocytes induced or not by oxidized LDL. Here we show the pro-apoptotic effect of these two drugs through two distinct signaling pathways and we highlight a synergistic effect of rapamycin on apoptosis induced by oxidized LDL. In conclusion, since immunosuppressive therapy using mycophenolate mofetil or rapamycin can increase the cell death in a monocyte cell line, this treatment could exert similar eff...
1. The effect of silicon (Si) contained in drinking water and solid food on the intestinal absorp... more 1. The effect of silicon (Si) contained in drinking water and solid food on the intestinal absorption of aluminium (Al) remains a matter of debate. The present study was designed to readdress this issue in the experimental animal, and to examine concomitantly the effects of citrate and the fasting state, respectively. 2. Three groups of young, non-fasted rats (n = 8 per group) were gavaged by solutions containing 3.8 ng of 26Al, 63 ng of 27Al, and either distilled water (< 0.1 mg/l Si) or commercial mineral water with a medium (6 mg/l) or high (14 mg/l) Si concentration. 3. Two other groups of eight non-fasted rats each received the same distilled water or high-Si gavage solution, respectively, together with a high citrate concentration (62 g/l). In each case the animals had free access to drinking water for 5 days before and 2 days after the gavage, containing the same Si concentration as in the gavage solution. A sixth group of eight rats was gavaged by low-Si, Al and distilled...
Vitamin status and role in end stage renal disease (ESRD) is controversial. This study was aimed ... more Vitamin status and role in end stage renal disease (ESRD) is controversial. This study was aimed at assessing vitamin A, E, B12, and folic acid status in Tunisian ESRD patients and testing their predictive value for overall mortality and cardiovascular events (CVE). We examined plasma vitamin A, E, B12, and folic acid in 115 ESRD patients and looked for any correlation with all-cause mortality and CVE after a six year follow-up. Vitamin A and E were determined by HPLC and vitamin B12 and folic acid were determined by enzyme immunoassay. At enrolment, plasma vitamin A was higher in patients than controls, while plasma vitamin B12 was higher in HD patients. No significant differences were observed for plasma vitamin E and folic acid concentrations between patients and controls. Folic acid and vitamin B12 levels were higher in supplemented patients. During the follow-up period, 17 patients were lost, 15 died, and 36 presented a CVE. Survival analysis showed that mortality and/or CVE tr...
As part of a tender AP-HP Paris Hospitals, an assessment of the reliability record of five blood ... more As part of a tender AP-HP Paris Hospitals, an assessment of the reliability record of five blood glucose monitoring systems (BGMSs) (Optium Xceed (Abbott), Contour TS (Bayer), One Touch Ultra (Lifescan), Stat Strip Xpress (Nova) and Accu Check (Roche) and an evaluation of their sensitivity to changes in hematocrit were conducted in 4 hospitals of Paris. In terms of inaccuracy, all BGMSs have submitted CV repetability under the limits of acceptability. One BGMS (Lifescan) presented a CV of reproducibility outside limit of acceptability (13.1%). The inaccuracy was measured by a comparison method on multiparameter analyser relative to the hexokinase method for two sites, the glucose oxidase for the two others. The coefficients of correlation varied from 0.8405 to 0.9303. However, according to both defined acceptability criteria (absolute value difference between the result acquired on analyzer and those determined with the BGMS), the percentage of results outside acceptability was abov...
This study was aimed to determine the prevalence of several classical and non-classical cardiovas... more This study was aimed to determine the prevalence of several classical and non-classical cardiovascular risk factors, and to test their association with cardiovascular events in Tunisian patients with end-stage renal disease. A total of 35 chronic renal failure, 50 hemodialysed and 30 renal transplant recipient patients and 31 healthy subjects were included. Hypertension, elevated plasma concentrations of total homocysteine, fibrinogen, C-reactive protein, and lipoprotein(a) were highly prevalent in patients, whereas, smoking, hypertriglyceridemia, hypercholesterolemia, hypoHDLemia, and hypoalbuminemia were less common. In univariate analysis, cardiovascular events were associated with age, hypertension, and the top quartile of the total homocysteine and C-reactive protein values. When controlling for several potential confounding factors, cardiovascular events remained associated with age, hypertension (OR, 7.07; 95% CI, 1.76-28.34; P=0.01), and the top quartile of total homocystein...
Progrès en urologie : journal de l'Association française d'urologie et de la Société française d'urologie, 2003
More than ten per cent of stones are associated with a urinary tract abnormality. To verify wheth... more More than ten per cent of stones are associated with a urinary tract abnormality. To verify whether the malformation influences stone composition, we studied the composition of stones observed in fifteen urological abnormalities. This study is based on 1,461 stones associated with a clearly defined malformation analysed by infrared spectroscopy plus 402 bladder stones in men with benign prostatic hyperplasia. In this series of 1,863 abnormalities, 732 (39.3%) involved the kidney, 561 (30.1%) involved the ureter and 570 (30.6%) involved the lower tract. Whewellite stones were predominant in all renal abnormalities with the exception of cysts, which were mainly associated with uric acid. The main differences concerned the second constituent: weddellite in horseshoe kidneys, carbapatite in Cacchi-Ricci disease and caliceal abnormalities. Struvite was uncommon (<10%). Whewellite was the main component in ureteric abnormalities except for megaureter and reflux in which carbapatite was...
Progrès en urologie : journal de l'Association française d'urologie et de la Société française d'urologie, 2001
High urine volume is known to be an effective measure for preventing stone recurrence. However, o... more High urine volume is known to be an effective measure for preventing stone recurrence. However, only few studies have investigated its effects on crystalluria and spontaneous passage of calculi. The aim of the study was to assess the effects of high diuresis on stone expulsion and recurrence. 219 patients were consulting for a first stone episode in Urology units in the Mostaganem area between September 1996 and December 1999. All stones were under 6 mm in size. The patients were divided in two groups: group I included 129 patients (68 males, 61 females) who agreed to be on a high water intake, at least 3 liters per day, over a two months period and to be followed periodically by crystalluria examination in the first morning urine; group II included 90 patients (63 males, 27 females) who declined diuresis advice and urine collection for crystalluria examination. First morning urine collected in patients of group I were examined before (2.95 voidings per subject) and while on diuresi...
1. To determine whether treatment with octreotide, a somatostatin analogue, may diminish or preve... more 1. To determine whether treatment with octreotide, a somatostatin analogue, may diminish or prevent long-term diabetic renal hypertrophy and nephropathy, uninephrectomized streptozotocin-diabetic rats maintained under moderate glycaemic control (approximately 300 mg/dl) were treated with either placebo (n = 10 rat/group) or octreotide for 14 weeks. Uninephrectomized non-diabetic rats given either placebo or octreotide served as controls. 2. Average body weight was diminished and kidney weight, daily urinary protein excretion, glomerular filtration rate and renal plasma flow were elevated in both diabetic groups relative to controls. 3. Administration of octreotide reduced average body weight and packed cell volume in non-diabetic and diabetic rats compared with their respective controls, but did not affect glomerular hyperfiltration or the increase in urinary protein excretion. 4. Histological examination at 14 weeks disclosed unequivocal glomerular hypertrophy and mild glomerular a...
Intestinal calcium absorption has been shown to include two processes, a saturable transcellular ... more Intestinal calcium absorption has been shown to include two processes, a saturable transcellular movement and a non-saturable paracellular pathway. The potential utility of cell monolayers for studying transepithelial intestinal calcium transport has already been demonstrated; however, simultaneous evaluation of the contribution of the saturable transcellular and of the non-saturable paracellular processes to the total transepithelial transport has not yet been attempted. The aim of this study was to investigate the contribution both of transcellular and paracellular transport processes to the total transepithelial calcium transport in two cell culture monolayers. Caco-2 cells and a clone derived from HT-29 cells (HT29-Cl.19A), two cell lines derived from colon adenocarcinomas which are known to be able to exhibit typical enterocytic differentiation, were used. Cell monolayers were grown on a permeable support and used after 15 days of culture when these cells express enterocytic differentiation and high transepithelial resistance. Isotopic transport rate measurements were performed in the absence of a chemical gradient. The paracellular route was evaluated using [ 3 H]mannitol. Calcium and [ 3 H]mannitol transport rates across cell monolayers were not significantly different. Augmentation of calcium uptake by 200 mM sorbitol did not significantly increase calcium or mannitol transepithelial transport; however, calcium accumulation in the cells was increased by about 200%. Modulation of the monolayer permeability by addition of 10 nM vasoactive intestinal polypeptide (VIP) or 0.5 mM carbachol treatment, which respectively increased and decreased the transepithelial resistance, consequently modified calcium and mannitol transport in a parallel manner. Our results show that Caco-2 and HT29-Cl.19A cell monolayers are good models for studying the calcium paracellular transport pathway. & k w d : Key words Transepithelial calcium transport • Caco-2 • HT-29 • Paracellular pathway& b d y :
France and director at INSERM. In addition to fundamental research studies in her career on hepat... more France and director at INSERM. In addition to fundamental research studies in her career on hepatitis B and Crelated liver carcinogenesis and calcium signalling, she has focused on applied research, targeting the domains of predictive oncology and prenatal diagnosis; her research activity led to the discovery and development of ISET (isolation by size of epithelial tumour/trophoblastic cells) for the characterization of circulating tumour and trophoblastic cells, thus permitting non-invasive cancer diagnostics and non-invasive prenatal diagnosis and leading to high-level publications and numerous awards.
Platelet cytosolic free calcium concentration ([Ca2+]i) and intracellular pH (pH i) (including th... more Platelet cytosolic free calcium concentration ([Ca2+]i) and intracellular pH (pH i) (including their responses to thrombin), as well as erythrocyte [Ca2+]i and 45Ca2+ influx, were studied in Lyon hypertensive (LH) and normotensive (LN) rats aged 3 months. Platelets of LH rats were characterized by substantially elevated basal [Ca2+]i values, higher [Ca2+]i levels after thrombin stimulation, and enhanced initial rate of thrombin-induced Mn 2+ entry through receptor-operated Ca 2+ channels. Basal platelet pH i values were not significantly different in LH and LN animals but thrombin elicited a significant alkalinization only in LH platelets. Erythrocytes of LH rats had an enhanced initial rate of 45Ca2+ and tended to elevated [Ca2+]i levels. Our data indicate profound alterations in cell Ca 2+ handling in platelets and erythrocytes of LH rats, similar to those previously described in spontaneously hypertensive rats of the Okamoto-Aoki strain. The analysis of the relations between blood pressure, plasma lipids, and cell Ca 2+ handling suggested that triglycerides, but not cholesterol, might be involved in altered platelet Ca 2+ handling in LH rats.
Carnitine deficiency has recently been incriminated in the pathogenesis of the disturbed lipid me... more Carnitine deficiency has recently been incriminated in the pathogenesis of the disturbed lipid metabolism observed in hemodialysis patients. The present study was performed to investigate the effects of L-carnitine administration on the lipid metabolism of rats with experimental chronic renal failure as compared to normal rats. Three groups of rats were studied: the first had induced chronic uremia, the second was sham-operated and pair-fed with the first, and the third was sham-operated and fed ad libitum. Serum triglycerides were significantly higher in uremic rats than in control animals of both groups. In addition to triglycerides, serum total cholesterol and phospholipids were also increased in uremic rats. The fractional clearance rate of Intralipid [K2(%)] was decreased in uremic as compared to control animals. The in vivo oxidation of radiolabeled palmitate was lower in uremic than in ad libitum-fed control animals but not lower than in pair-fed control rats. The daily oral administration of L-carnitine to uremic rats was associated with stable serum triglycerides. On the contrary, serum triglycerides increased significantly in the untreated uremic rats over the same period of time. Serum total cholesterol and phospholipids remained similar in the presence and the absence of L-carnitine treatment. The intravenous fat tolerance test of carnitine-supplemented uremic rats improved slightly, although not significantly, when compared to that of untreated uremic rats. In conclusion, oral L-carnitine supplementation in chronically uremic rats had only modest or no effects on several plasma lipid parameters.(ABSTRACT TRUNCATED AT 250 WORDS)
Uploads
Papers by Bernard Lacour