B Lacour

Université de Picardie Jules Verne, Amiens, Picardie, France

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Publications (322)1296.24 Total impact

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    ABSTRACT: 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 α 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.
    Atherosclerosis 04/2013; · 3.71 Impact Factor
  • Bernard Lacour
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    ABSTRACT: This review concerns the physiology of the kidney. The first chapter depicts briefly the anatomy of the kidney. The second chapter is focused on the glomerular filtration, with a présentation of the process governing the formation of the pre-urine in the Bowman space, a study of the physiological régulation of glomerular filtration rate (GFR), the normal values of GFR, the évaluation of this glomerular filtration function and a rapid glimpse on glomerular pathologies. The third chapter is about the tubular functions of reabsorption and sécrétion at the level of the différent parts of the néphron. We develop the transport mechanisms of reabsorption of glucose, amino-acids, proteins of low molecular weight and main ions (bicarbonates, phosphates, Na+, CI− and Ca2+) as well as the process of sécrétion concerning H+ ions, ammoniac and drugs in proximal part of the tubule. Then the respective functions of the two descending and ascending limbs of Henlé are presented before studying those of the distal tubule, through the rôle of principal cells, intercalated A and B cells in the maintain of hydromineral and acid-base balance. The study of the différent parts of the tubule ends with the collecting duct and the rôle played by anti-diuretic hormone in the concentration of the urines. The last chapter concerns the 3 endocrine functions of kidney, with synthesis of renin, erythropoietin, and 1,25(OH)2 cholecalciferol.
    Revue Francophone des Laboratoires 04/2013; 2013(451):25–37.
  • Bernard Lacour, Ziad Massy
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    ABSTRACT: This review summarizes the current knowledge about acute renal failure (ARF). It begins by reminding the different etiologies and the biological elements to differentiate the diagnosis between functional and organic ARF. It stresses the importance to classify ARF according to its magnitude, taking into account both serum creatinine concentrations and in urinary output modifications. It emphasizes the importance of new very interesting biological markers such as NGAL (neutrophil-gelatinase associated lipocalin) in order to have an early diagnosis of ARF before the modification of sérum créatinine, although the use of these markers at present time are restricted to certain high risk patients. Finally, it underlines the importance of evaluating the kidney function 2 months after the time of ARF, in order to detect those who having recovered a normal renal function from those who having begun or deteriorated a chronic renal disease, who should be managed according to appropriate guidelines.
    Revue Francophone des Laboratoires 04/2013; 2013(451):55–58.
  • Bernard Lacour, Ziad Massy
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    ABSTRACT: The present review summarizes our current knowledge about the diagnosis and the follow-up of patients with chronic renal failure as well as the management of end stage renal disease (ESRD) by dialysis or kidney transplantation. The first chapter underlines the pitfalls in the diagnosis of the chronic kidney disease (CKD) using the calculation or the estimation of glomerular filtration rate (GFR), and presents the current classification of CKD. The following chapter describes the different complications associated with CKD, considering the pathophysiology and the management of each complication. The third chapter concerns the practical organization for the follow-up and the management of CKD patients at each stage. The fourth chapter is dedicated to the different dialysis modalities for ESRD patients, with a special focus on specific complications related to hemodialysis or peritoneal dialysis. The last chapter concerns kidney transplantation with a comprehensible description of the immunosuppressive therapy and their side-effects.
    Revue Francophone des Laboratoires 04/2013; 2013(451):59–73.
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    ABSTRACT: To confirm whether oral antibiotic treatment is as efficacious as sequential intravenous/oral antibiotic treatment in the prevention of renal scarring in children with acute pyelonephritis and scintigraphy-documented acute lesions. In a prospective multicenter trial, children aged 1 to 36 months with their first case of acute pyelonephritis, a serum procalcitonin concentration ≥0.5 ng/mL, no known uropathy, and a normal ultrasound exam were randomized into 2 treatment groups. They received either oral cefixime for 10 days or intravenous ceftriaxone for 4 days followed by oral cefixime for 6 days. Patients with acute renal lesions detected on early dimercaptosuccinic acid scintigraphy underwent a follow-up scintigraphy 6 to 8 months later. The study included 171 infants and children. There were no significant differences between the 2 groups in any clinical characteristic. Initial scintigraphy results were abnormal for 119 children. Ninety-six children were measured for renal scarring at the follow-up scintigraphy (per protocol analysis population). The incidence of renal scarring was 30.8% in the oral treatment group and 27.3% for children who received the sequential treatment. Although this trial does not statistically demonstrate the noninferiority of oral treatment compared with the sequential treatment, our study confirmed the results of previously published reports and therefore supports the use of an oral antibiotic treatment of primary episodes of acute pyelonephritis in infants and young children.
    PEDIATRICS 02/2012; 129(2):e269-75. · 4.47 Impact Factor
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    ABSTRACT: The aim of this study was to address whether NP might be a predictive factor for severity of CF. The authors collected data from the literature on NP as a unique or associated sign in CF and reviewed the clinical and molecular aspects of CF associated with NP. CF genotypes and clinical severity in NP(+) vs. NP(-) patients were reviewed, taking into account pulmonary function, frequency of P. aeruginosa lung infection, frequency of allergy, nutritional status, and exocrine pancreatic function. The CFTR gene was also analyzed in a patient with isolated severe NP as the unique feature of CF. This review of the literature showed a `milder` phenotype in `NP+` vs. `NP-` CF patients, contrasting with a marked association between NP and `severe` CF mutations. In addition, a complex genotype was identified, associating four heterozygous variants, namely p.Q493X (a severe mutation) on the paternal allele, and p.V562I, p.A1006E, and (TG)11(T)5 (IVS8-5T) on the maternal allele, in a case of CF presenting as isolated NP. The authors speculate that genetic/environmental factors associated with NP might attenuate the functional impact of `severe` CF mutations. The overrepresentation of CF carriers among patients with isolated NP also advocates the need for CFTR molecular screening in such populations for genetic counselling purposes.
    Rhinology 09/2011; 49(3):347-55. · 1.72 Impact Factor
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    ABSTRACT: Atherosclerosis and vascular calcification (VC) progression in chronic kidney disease is favored by disturbances of mineral metabolism. We compared the effect of phosphate binder lanthanum (La) carbonate with sevelamer-HCl on atherosclerosis, VC and bone structure and function in mice with chronic renal failure (CRF). Apolipoprotein E-deficient (apoE(-/-)) mice were randomized to one non-CRF and three CRF groups, fed with standard diet (one non-CRF and one CRF) or diet supplemented with either 3% lanthanum carbonate (La3%) or 3% sevelamer-HCl (Sev3%). Both La3% and Sev3% supplemented CRF mice displayed a decrease of serum phosphorus, calcification at both intimal and medial aortic sites and atherosclerosis. This was associated with a reduction of plaque Type I collagen expression by both binders and of positive nitrotyrosine staining in response to sevelamer-HCl only. Increased mineral apposition and bone formation rates in unsupplemented CRF mice were reduced by Sev3% but not by La3%. The beneficial effects of La carbonate and sevelamer-HCl on the progression of VC and atherosclerosis in CRF mice could be mainly due to a decrease in phosphate retention and likewise a reduction of arterial Type I collagen expression. The effect of La carbonate differed from that of sevelamer-HCl in that it did not appear to exert its vascular effects via changes in oxidative stress or bone remodeling in the present model.
    Nephrology Dialysis Transplantation 06/2011; 27(2):505-13. · 3.37 Impact Factor
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    ABSTRACT: Dietary supplements in polyunsaturated fatty acids (PUFA), particularly omega-3, are well known for their beneficial effects in preventing cardiovascular diseases (CVD). The aim of this study was to determine the role of PUFA on the modulation of apoptosis induced by hypochlorous acidoxidized LDL (HOCl-oxLDL) in U937 cells. We tested the effect of monocyte cell line U937 supplementation with eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (ARA) or oleic acid (OA) on the modulation of HOCl-oxLDL-induced apoptosis. First, we showed the incorporation of fatty acids in the cellular membrane in U937 cells. Then, we showed that both EPA and ARA exerted a pro-apoptotic effect through the intrinsic mitochondrial apoptotic pathway including the dissipation of mitochondrial membrane potential followed by cardiolipin depletion, the downstream activation of caspase-3 and the increase in DNA fragmentation. The pro-apoptotic effect of EPA or ARA was completely blocked in U937/Bcl-2 cells. A new mechanism of dietary supplements in PUFA with likely consequences in apoptosis could be suggested through the mitochondrial pathway in monocytes.
    Journal of atherosclerosis and thrombosis 02/2011; 18(6):494-503. · 2.93 Impact Factor
  • L Rached, B Lacour, M Daudon
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    ABSTRACT: The aim of our study was to determine the nature of urinary stones and the main lithogenic process in patients with multiple sclerosis who developed secondary urolithiasis. This is a retrospective study of 60 urinary stones from 49 patients with lithiasis including 30 women and 19 men. The stones have been analyzed by optical microscopy and infrared spectroscopy. Our study clearly showed the net preponderance of phosphatic stones. Urinary stones were mainly located in the upper urinary tract (2/3 of cases). A particularly high frequency of struvite was observed among these stones (65% of cases in women and 45% of cases in men), thus suggesting the main lithogenic mechanism in multiple sclerosis patients was a urinary tract infection by urea splitting-bacteria. The second lithogenic process among these patients was metabolic. The high frequency of weddellite and brushite, especially in men, suggested that mainly hypercalciuria was involved in these metabolic stones. Urolithiasis in multiple sclerosis was mainly due to urinary tract infection, especially in women. Urinary tract infection related to bladder and sphincter disorders is extremely frequent and polymorphic in multiple sclerosis. Hence the importance of providing appropriate care to prevent complications of urinary tract infections and, especially, the ascending migration of microorganisms and the risk of pyelonephritis and of infectious kidney stones.
    Progrès en Urologie 02/2011; 21(2):102-8. · 0.80 Impact Factor
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    ABSTRACT: 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 trend to be lower for high folic acid levels (Log Rank = 0.098). Cox's regression analysis showed that high levels of folic acid are inversely related to all-cause mortality and/or CVE [Hazard ratio (95% confidence interval), 0.255 (0.08 - 0.740); p = 0.012]. Plasma vitamins A, E, B12, and folic acid concentrations are usually normal in Tunisian ESRD patients. High folic acid levels are associated with fewer CVE and better survival. However, as uremia could be associated with functional vitamin deficiency, maintaining high plasma vitamin levels by adequate nutrition and tolerable supplementation would be beneficial in ESRD patients.
    Clinical laboratory 01/2011; 57(11-12):939-46. · 0.92 Impact Factor
  • L. Rached, B. Lacour, M. Daudon
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    ABSTRACT: Objective The aim of our study was to determine the nature of urinary stones and the main lithogenic process in patients with multiple sclerosis who developed secondary urolithiasis.Patients and methodThis is a retrospective study of 60 urinary stones from 49 patients with lithiasis including 30 women and 19 men. The stones have been analyzed by optical microscopy and infrared spectroscopy.ResultsOur study clearly showed the net preponderance of phosphatic stones. Urinary stones were mainly located in the upper urinary tract (2/3 of cases). A particularly high frequency of struvite was observed among these stones (65% of cases in women and 45% of cases in men), thus suggesting the main lithogenic mechanism in multiple sclerosis patients was a urinary tract infection by urea splitting-bacteria. The second lithogenic process among these patients was metabolic. The high frequency of weddellite and brushite, especially in men, suggested that mainly hypercalciuria was involved in these metabolic stones.Conclusion Urolithiasis in multiple sclerosis was mainly due to urinary tract infection, especially in women. Urinary tract infection related to bladder and sphincter disorders is extremely frequent and polymorphic in multiple sclerosis. Hence the importance of providing appropriate care to prevent complications of urinary tract infections and, especially, the ascending migration of microorganisms and the risk of pyelonephritis and of infectious kidney stones.
    Progrès en Urologie. 01/2011; 21(2):102-108.
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    ABSTRACT: Chronic kidney disease (CKD) is associated with disorders of mineral and bone metabolism (MBD) which include renal osteodystrophy and vascular calcifications. This is of clinical concern because the high risk of cardiovascular (CVD) complications observed in uremic patients may be linked with bone disease. In this context, our aim was to characterize the bone lesions in CKD-apolipoprotein E-deficient mice (apoE(-/-)) and analyze their relationships with the vascular calcifications which these animals develop rapidly in this model. With ApoE being also involved in bone metabolism, we compared the effects of CRF on the bone of apoE(-/-) mice to those observed in wild type mice (WT) of the same genetic background, C57/BL6. After CRF creation or sham surgery, 10 week-old female apoE(-/-) and WT mice were randomized to 4 groups (n=10-14/group) and fed with standard diet. Eight weeks later, animals were euthanized. Serum, aorta and femur were sampled. Femurs were imaged with 3-dimensional microtomography (microCT) and processed for bone histomorphometry (BHM). Additional quantitative histology was performed on atherosclerotic and calcified lesions in the aortas of apoE(-/-) mice. First, apoE(-/-) mice exhibited higher cortical (10%) and trabecular (31%) bone mass than WT. CRF led to a further increase in trabecular BV/TV in WT and in apoE(-/-) mice (10.2% and 77.2%, respectively). We observed a similar increase in osteoid surface and osteoblastic parameters in CRF mice of both genotypes while resorption parameters were less augmented by CRF in apoE(-/-) mice. Finally, based on either BHM or microCT we found positive correlations between the extent of atherosclerotic lesions and bone volume parameters, and between the size of plaque calcification and osteoclast parameters in apoE(-/-) mice. ApoE deficiency is associated with an increase in bone mass and volumetric mineral density in 20 week-old female mice. Bone mass is further increased, whereas bone mineral density is decreased, in response to CRF in association with histological features of osteitis fibrosa. Finally, our findings of correlations between changes in bone and aortic lesions in apoE(-/-) mice, are compatible with the hypothesis of a link between bone and vascular disease and require further study.
    Bone 07/2010; 47(1):156-63. · 3.82 Impact Factor
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    ABSTRACT: We compared the apoptotic mechanism involved in U937 human monocytic cell line in presence of oxidized low-density lipoproteins (oxLDL) obtained after treatment with hypochlorous acid (HOCl) or copper (Cu). Both types of oxLDL induced U937 apoptotic cell death via the mitochondrial pathway. In contrast to HOCl-oxLDL, Cu-oxLDL induced apoptosis via a caspase-independent mechanism, with no activation of pro-caspase-3, but via the release of apoptosis inducing factor (AIF) from mitochondria. The apoptotic program of the monocyte differs depending on the mode of LDL oxidation, based on differences in the oxidatively modified components of the two oxLDL types.
    Biochemical and Biophysical Research Communications 02/2010; 393(4):783-7. · 2.41 Impact Factor
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    ABSTRACT: Lanthanum (La) carbonate is a new treatment for hyperphosphatemia. We tested the effects of oral La carbonate and aluminum hydroxide, respectively, on tissue accumulation and liver function in rats with chronic renal failure (CRF). Adult male non-CRF and CRF rats were randomly assigned to 3 groups receiving either standard diet (St.D), or the same diet supplemented with 3% La carbonate (non-CRF La vs. CRF La) or 3% aluminum hydroxide (non-CRF Al vs. CRF Al). After 12 weeks, serum phosphorus was decreased in both CRF La and Al groups. Urinary La and Al excretion was increased in these two groups, and so was liver and bone La content, and liver Al content. Both total body and liver weight were decreased in CRF La and CRF Al rats. Liver cell proliferation was decreased in these groups, while plasma total alkaline phosphatases and alanine aminotransferase were increased. Hepatic total cytochrome p450 content was reduced in CRF La, but not in CRF Al rats. Long-term oral La overload in rats with CRF was associated with a decrease in liver (and total body) weight and mild alterations of liver function, as was Al overload, possibly as a consequence of trace element accumulation.
    Nephron Experimental Nephrology 01/2010; 115(4):e112-21. · 2.01 Impact Factor
  • Archives De Pediatrie - ARCHIVES PEDIATRIE. 01/2010; 17(6):34-34.
  • Transplantation 01/2010; 90. · 3.78 Impact Factor
  • Reproductive Biomedicine Online - REPROD BIOMED ONLINE. 01/2010; 20.
  • Journal of Cystic Fibrosis - J CYST FIBROS. 01/2010; 9.
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    ABSTRACT: Procalcitonin (PCT) is an accurate marker for differentiating bacterial infection from non-infective causes of inflammation or viral infection. However, there is only one study in children which tested procalcitonin as a diagnostic aid in skeletal infections. With this study we sought to evaluate the sensitivity, specificity and predictive values of procalcitonin for identifying bone and joint infection in children evaluated in the emergency department for non traumatic decreased active motion of a skeletal segment. Patients aged 1 month to 14 years were prospectively included in the emergency department when suspected for osteomyelitis or septic arthritis. Procalcitonin levels, C reactiv protein, white blood cell count were measured and bacteriological samples were collected before initiation of antibiotic treatment. Patients were assigned to 3 groups according to the degree of suspected infection: group 1 confirmed infection, group 2 presumed infection and group 3 non infected patients. Three hundred thirty nine patients were included (118 girls and 221 boys). Group 1 comprised 8 patients (2 had PCT levels > 0.5 ng/ml). Two had osteomyelitis and 6 septic arthritis. Forty children were incuded in group 2 (4 had PCT levels > 0.5 ng/ml). Eighteen had presumed osteomyelitis and 22 presumed septic arthritis. Group 3 comprised 291 children (9 PCT levels > 0.5 ng/ml) who recovered without antibiotic treatment. The specificity of the PCT as a marker of bacterial infection (comparing Group 1 and Group 3) was 96.9% [95% CI, 94.2-98.6], the sensitivity 25% [95% CI, 3.2-65.1], the positive predictive value (PPV) 18.2% [95% CI, 2.3-51.8] and the negative predictive value (NPV) 97.9% [95% CI, 95.5-99.2]. PCT is not a good screening test for identifying skeletal infection in children. Larger studies are needed to evaluate still more the place of PCT measurements in the diagnosis of osteomyelitis and septic arthritis.
    Italian Journal of Pediatrics 11/2009; 35(1):33. · 1.34 Impact Factor
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    ABSTRACT: Oxidized low density lipoprotein (Ox-LDL) is a well-established risk factor in atherosclerosis and lysophosphatidylcholine (LysoPtdCho) is considered to be one of the major atherogenic component of Ox-LDL. The purpose of this work was to investigate the effects of two membrane n-3 long chain polyunsaturated fatty acids (n-3 PUFAs), EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) compared to n-6 PUFA, ARA (arachidonic acid), on the activation of endothelial NO synthase (eNOS) by histamine in Ea hy 926 endothelial cells incubated during 24 h in the presence or the absence of LysoPtdCho. DHA (50 muM) produced a ROS induction in cells and aggravated the LysoPtdCho-induced oxidative stress. It did not modify the basal eNOS activity but impaired the stimulation of eNOS induced by histamine and was unable to correct the deleterious effect of LysoPtdCho on histamine-stimulated eNOS activity or phosphorylation of Ser 1177. In contrast, EPA (90 muM) did not modify the ROS level produced in the presence or absence of LysoPtdCho or basal eNOS activity and the stimulating effect of histamine on eNOS. However, it diminished the deleterious effect of LysoPtdCho as well as on the histamine-stimulated eNOS activity on the phosphorylation on Ser 1177 of eNOS. The beneficial effect of EPA but not DHA on endothelial eNOS activity in Ea hy 926 could be also partially due to a slight decrease in membrane DHA content in EPA-treated cells. Consequently, the equilibrium between NO generated by eNOS and ROS due to oxidative stress could explain, in part, the beneficial effect of EPA on the development of cardiovascular diseases. By contrast ARA an n-6 PUFA was devoid of any effect on ROS generation or eNOS activity in the basal state or after histamine-induced stimulation. In vivo experiments should be undertaken to confirm these results.
    Lipids 03/2009; 44(3):225-35. · 2.56 Impact Factor

Publication Stats

4k Citations
1,296.24 Total Impact Points

Institutions

  • 2011–2013
    • Université de Picardie Jules Verne
      Amiens, Picardie, France
  • 1985–2013
    • Hôpital Universitaire Necker
      Lutetia Parisorum, Île-de-France, France
  • 2005–2011
    • Université Paris-Sud 11
      • • Lipides Membranaires et Régulation Fonctionnelle du Coeur et des Vaisseaux
      • • Faculté de Pharmacie
      Paris, Ile-de-France, France
  • 2008
    • Université René Descartes - Paris 5
      Lutetia Parisorum, Île-de-France, France
  • 2006–2008
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
    • Hannover Medical School
      Hanover, Lower Saxony, Germany
    • Hôpital La Pitié Salpêtrière (Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix")
      Lutetia Parisorum, Île-de-France, France
  • 2003–2008
    • La Rabta Hospital Tunis
      Tunis-Ville, Tūnis, Tunisia
  • 1990–2008
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 1988–2005
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 1997
    • University of Sidi-Bel-Abbes
      • Department of Chemistry
      Sidi Bel Abbès, Wilaya de Sidi Bel Abbes, Algeria
  • 1996
    • University of Florida
      • College of Medicine
      Gainesville, FL, United States
  • 1989
    • Oregon Health and Science University
      • Division of Nephrology & Hypertension
      Portland, OR, United States