The main soluble form of the receptor for advanced glycation end-products (sRAGE) is elevated dur... more The main soluble form of the receptor for advanced glycation end-products (sRAGE) is elevated during acute respiratory distress syndrome (ARDS). However other RAGE isoforms and multiple ligands have been poorly reported in the clinical setting, and their respective contribution to RAGE activation during ARDS remains unclear. Our goal was therefore to describe main RAGE isoforms and ligands levels during ARDS. 30 ARDS patients and 30 mechanically ventilated controls were prospectively included in this monocenter observational study. Arterial, superior vena cava and alveolar fluid levels of sRAGE, endogenous-secretory RAGE (esRAGE), high mobility group box-1 protein (HMGB1), S100A12 and advanced glycation end-products (AGEs) were measured in duplicate ELISA on day 0, day 3 and day 6. In patients with ARDS, baseline lung morphology was assessed with computed tomography. ARDS patients had higher arterial, central venous and alveolar levels of sRAGE, HMGB1 and S100A12, but lower levels o...
The Journal of Clinical Endocrinology & Metabolism, 2015
During pregnancy, aquaporins (AQPs) expressed in fetal membranes are essential for controlling th... more During pregnancy, aquaporins (AQPs) expressed in fetal membranes are essential for controlling the homeostasis of the amniotic volume, but their regulation by insulin was never explored in diabetic women. The aim of our study was to investigate the involvement of AQP 1, 3, 8, and 9 expressed in fetal membranes in diabetic parturient women, and the control of their expression by insulin. From 129 fetal membranes in four populations, (controls, type 1 (T1D), type 2 (T2D) and gestational diabetes (GD)), we established an expression AQPs profile. In a second step, the amnion was used to study the control of the expression and functions of AQPs 3 and 9 by insulin. The expression of transcripts and proteins of AQPs was studied by qRT-PCR and ELISA. We analyzed the regulation by insulin of the expression of AQPs 3 and 9 in the amnion. A tritiated glycerol test enabled us to measure the impact of insulin on the functional characteristics. Using an inhibitor of phosphatidylinositol 3-kinase (PI3K) we analyzed the insulin intracellular signaling pathway. The expression of AQP3 protein was significantly weaker in groups T2D and GD. In non-diabetic fetal membranes, we showed for the amnion (but not for the chorion) a significant repression by insulin of the transcriptional expression of AQPs 3 and 9, which was blocked by a PI3K inhibitor. In fetal membranes, the repression of AQP3 protein expression and functions observed in vivo is allowed by the hyperinsulinism described in pregnant women with T2D or GD.
The soluble form of the receptor for advanced glycation end-products (sRAGE) is elevated and corr... more The soluble form of the receptor for advanced glycation end-products (sRAGE) is elevated and correlated with severity in patients with acute respiratory distress syndrome (ARDS). The impact of ventilator settings on plasma levels of sRAGE, in patients with or without pre-existing lung injury, remains under-investigated to date. Our objective was to assess the effects of a lung-protective ventilation strategy (combining low tidal volume, positive end-expiratory pressure and recruitment maneuvers), as compared with a non-protective approach (with high tidal volume and zero end-expiratory pressure), on plasma levels of sRAGE in patients without lung injury undergoing major abdominal surgery. Plasma samples were obtained from 95 patients enrolled in a large randomized controlled trial of lung-protective ventilation for major abdominal surgery. Plasma levels of sRAGE were measured in duplicate with an enzyme-linked immunoassay on day 1, immediately after surgery, and on postoperative day...
American Journal of Respiratory and Critical Care Medicine, 2015
Levels of the soluble form of the receptor for advanced glycation end-products (sRAGE) are elevat... more Levels of the soluble form of the receptor for advanced glycation end-products (sRAGE) are elevated during acute respiratory distress syndrome (ARDS) and correlate with severity and prognosis. Alveolar fluid clearance (AFC) is necessary for the resolution of lung edema, but is impaired in the majority of ARDS patients. No reliable marker of this process has been investigated to date. To verify whether sRAGE could predict AFC during ARDS. Anesthetized CD-1 mice underwent orotracheal instillation of hydrochloric acid. At specified time-points, lung injury was assessed by analysis of blood gases, alveolar permeability, lung histology, AFC and plasma/bronchoalveolar fluid measurements of pro-inflammatory cytokines and sRAGE. Plasma sRAGE and AFC rates were also prospectively assessed in thirty patients with ARDS. The rate of AFC was inversely correlated with sRAGE levels in the plasma and the bronchoalveolar fluid of both acid-injured mice (Spearman's rho = -0.73 and -0.69, respectively, P<10-3), and plasma sRAGE correlated with AFC in patients with ARDS (Spearman's rho = -0.59, P<10-3). Similarly, sRAGE levels were significantly associated with lung injury severity, and decreased over time in mice while AFC was restored and lung injury resolved. Our results indicate that sRAGE levels could be a reliable predictor of impaired AFC during ARDS, and should stimulate further studies on the pathophysiologic implications of RAGE axis in the mechanisms leading to edema resolution. Clinical trial registration available at www.clinicaltrials.gov, ID NCT00811629.
... David Crettaz, Lynne Thadikkaran, Denis Gallot, Pierre-Alain Queloz, Vincent Sapin, Joël S. R... more ... David Crettaz, Lynne Thadikkaran, Denis Gallot, Pierre-Alain Queloz, Vincent Sapin, Joël S. Rossier, Patrick Hohlfeld, and Jean-Daniel Tissot ... Jauniaux E, Jurkovic D, Gulbis B, Liesnard C, Lees C, Campbell S. Materno-fetal immunoglobulin transfer and passive immunity during ...
Retinoids (active derivatives of vitamin A) were already demonstrated to be important morphogenes... more Retinoids (active derivatives of vitamin A) were already demonstrated to be important morphogenes and their implication at the placental and fetal level was already established. A new field of research is now developed in order to show their role on fetal membranes constituted by amnion and chorion. To describe the role of retinoids on these membranes, our studies were focused on target gene research. Firstly, all metabolism enzymes needed to vitamin A pathways were demonstrated to be present and active in signal transduction. Secondly, a bioinformatic analysis was performed to assess a list of potential target genes that could be classified in different biological pathways (inflammation, retinoids, hormones, vascularization, extracellular matrix and water homeostasis). Then, it was demonstrated that the gene coding for PLAT, implied in the degradation of extracellular matrix during programmed or premature rupture of membranes, is regulated by retinoids in a two steps mechanism. Fin...
Retinol (vitamin A) is a fat-soluble nutrient indispensable for a harmonious mammalian gestation.... more Retinol (vitamin A) is a fat-soluble nutrient indispensable for a harmonious mammalian gestation. The absence or excess of retinol and its active derivatives [i.e., the retinoic acids (RAs)] can lead to abnormal development of embryonic and extraembryonic (placental) structures. The embryo is unable to synthesize the retinol and is strongly dependent on the maternal delivery of retinol itself or precursors: retinyl esters or carotenoids. Before reaching the embryonic tissue, the retinol or the precursors have to pass through the placental structures. During this placental step, a simple diffusion of retinol can occur between maternal and fetal compartments; but retinol can also be used in situ after its activation into RA(1) or stored as retinyl esters. Using retinol-binding protein knockout model, an alternative way of embryonic retinol supply was described using retinyl esters incorporated into maternal chylomicrons. In the embryo, the principal metabolic event occurring for retin...
Objective. – To evaluate the neonatal morbidity and its risks factors in case of uncomplicated pr... more Objective. – To evaluate the neonatal morbidity and its risks factors in case of uncomplicated preterm rupture of membranes managed conservatively with subsequent planned delivery at 34 weeks of gestation.Patients and methods. – We studied retrospectively 42 consecutive neonates systematically delivered at 34 weeks of gestation after more than 48 hours of conservative management for uncomplicated preterm rupture of membranes. Conservative management was
Objective. – To compare the mode of delivery in two groups of patients selected by their response... more Objective. – To compare the mode of delivery in two groups of patients selected by their response after induction of labour with mifepristone.Patients and methods. – We studied retrospectively 89 cases of labour induction with viable children after 41 weeks of gestation. Bishop scores were less than 6. Patients were given 200 mg of mifepristone per day for 48 h. They were retrospectively divided
The main soluble form of the receptor for advanced glycation end-products (sRAGE) is elevated dur... more The main soluble form of the receptor for advanced glycation end-products (sRAGE) is elevated during acute respiratory distress syndrome (ARDS). However other RAGE isoforms and multiple ligands have been poorly reported in the clinical setting, and their respective contribution to RAGE activation during ARDS remains unclear. Our goal was therefore to describe main RAGE isoforms and ligands levels during ARDS. 30 ARDS patients and 30 mechanically ventilated controls were prospectively included in this monocenter observational study. Arterial, superior vena cava and alveolar fluid levels of sRAGE, endogenous-secretory RAGE (esRAGE), high mobility group box-1 protein (HMGB1), S100A12 and advanced glycation end-products (AGEs) were measured in duplicate ELISA on day 0, day 3 and day 6. In patients with ARDS, baseline lung morphology was assessed with computed tomography. ARDS patients had higher arterial, central venous and alveolar levels of sRAGE, HMGB1 and S100A12, but lower levels o...
The Journal of Clinical Endocrinology & Metabolism, 2015
During pregnancy, aquaporins (AQPs) expressed in fetal membranes are essential for controlling th... more During pregnancy, aquaporins (AQPs) expressed in fetal membranes are essential for controlling the homeostasis of the amniotic volume, but their regulation by insulin was never explored in diabetic women. The aim of our study was to investigate the involvement of AQP 1, 3, 8, and 9 expressed in fetal membranes in diabetic parturient women, and the control of their expression by insulin. From 129 fetal membranes in four populations, (controls, type 1 (T1D), type 2 (T2D) and gestational diabetes (GD)), we established an expression AQPs profile. In a second step, the amnion was used to study the control of the expression and functions of AQPs 3 and 9 by insulin. The expression of transcripts and proteins of AQPs was studied by qRT-PCR and ELISA. We analyzed the regulation by insulin of the expression of AQPs 3 and 9 in the amnion. A tritiated glycerol test enabled us to measure the impact of insulin on the functional characteristics. Using an inhibitor of phosphatidylinositol 3-kinase (PI3K) we analyzed the insulin intracellular signaling pathway. The expression of AQP3 protein was significantly weaker in groups T2D and GD. In non-diabetic fetal membranes, we showed for the amnion (but not for the chorion) a significant repression by insulin of the transcriptional expression of AQPs 3 and 9, which was blocked by a PI3K inhibitor. In fetal membranes, the repression of AQP3 protein expression and functions observed in vivo is allowed by the hyperinsulinism described in pregnant women with T2D or GD.
The soluble form of the receptor for advanced glycation end-products (sRAGE) is elevated and corr... more The soluble form of the receptor for advanced glycation end-products (sRAGE) is elevated and correlated with severity in patients with acute respiratory distress syndrome (ARDS). The impact of ventilator settings on plasma levels of sRAGE, in patients with or without pre-existing lung injury, remains under-investigated to date. Our objective was to assess the effects of a lung-protective ventilation strategy (combining low tidal volume, positive end-expiratory pressure and recruitment maneuvers), as compared with a non-protective approach (with high tidal volume and zero end-expiratory pressure), on plasma levels of sRAGE in patients without lung injury undergoing major abdominal surgery. Plasma samples were obtained from 95 patients enrolled in a large randomized controlled trial of lung-protective ventilation for major abdominal surgery. Plasma levels of sRAGE were measured in duplicate with an enzyme-linked immunoassay on day 1, immediately after surgery, and on postoperative day...
American Journal of Respiratory and Critical Care Medicine, 2015
Levels of the soluble form of the receptor for advanced glycation end-products (sRAGE) are elevat... more Levels of the soluble form of the receptor for advanced glycation end-products (sRAGE) are elevated during acute respiratory distress syndrome (ARDS) and correlate with severity and prognosis. Alveolar fluid clearance (AFC) is necessary for the resolution of lung edema, but is impaired in the majority of ARDS patients. No reliable marker of this process has been investigated to date. To verify whether sRAGE could predict AFC during ARDS. Anesthetized CD-1 mice underwent orotracheal instillation of hydrochloric acid. At specified time-points, lung injury was assessed by analysis of blood gases, alveolar permeability, lung histology, AFC and plasma/bronchoalveolar fluid measurements of pro-inflammatory cytokines and sRAGE. Plasma sRAGE and AFC rates were also prospectively assessed in thirty patients with ARDS. The rate of AFC was inversely correlated with sRAGE levels in the plasma and the bronchoalveolar fluid of both acid-injured mice (Spearman's rho = -0.73 and -0.69, respectively, P<10-3), and plasma sRAGE correlated with AFC in patients with ARDS (Spearman's rho = -0.59, P<10-3). Similarly, sRAGE levels were significantly associated with lung injury severity, and decreased over time in mice while AFC was restored and lung injury resolved. Our results indicate that sRAGE levels could be a reliable predictor of impaired AFC during ARDS, and should stimulate further studies on the pathophysiologic implications of RAGE axis in the mechanisms leading to edema resolution. Clinical trial registration available at www.clinicaltrials.gov, ID NCT00811629.
... David Crettaz, Lynne Thadikkaran, Denis Gallot, Pierre-Alain Queloz, Vincent Sapin, Joël S. R... more ... David Crettaz, Lynne Thadikkaran, Denis Gallot, Pierre-Alain Queloz, Vincent Sapin, Joël S. Rossier, Patrick Hohlfeld, and Jean-Daniel Tissot ... Jauniaux E, Jurkovic D, Gulbis B, Liesnard C, Lees C, Campbell S. Materno-fetal immunoglobulin transfer and passive immunity during ...
Retinoids (active derivatives of vitamin A) were already demonstrated to be important morphogenes... more Retinoids (active derivatives of vitamin A) were already demonstrated to be important morphogenes and their implication at the placental and fetal level was already established. A new field of research is now developed in order to show their role on fetal membranes constituted by amnion and chorion. To describe the role of retinoids on these membranes, our studies were focused on target gene research. Firstly, all metabolism enzymes needed to vitamin A pathways were demonstrated to be present and active in signal transduction. Secondly, a bioinformatic analysis was performed to assess a list of potential target genes that could be classified in different biological pathways (inflammation, retinoids, hormones, vascularization, extracellular matrix and water homeostasis). Then, it was demonstrated that the gene coding for PLAT, implied in the degradation of extracellular matrix during programmed or premature rupture of membranes, is regulated by retinoids in a two steps mechanism. Fin...
Retinol (vitamin A) is a fat-soluble nutrient indispensable for a harmonious mammalian gestation.... more Retinol (vitamin A) is a fat-soluble nutrient indispensable for a harmonious mammalian gestation. The absence or excess of retinol and its active derivatives [i.e., the retinoic acids (RAs)] can lead to abnormal development of embryonic and extraembryonic (placental) structures. The embryo is unable to synthesize the retinol and is strongly dependent on the maternal delivery of retinol itself or precursors: retinyl esters or carotenoids. Before reaching the embryonic tissue, the retinol or the precursors have to pass through the placental structures. During this placental step, a simple diffusion of retinol can occur between maternal and fetal compartments; but retinol can also be used in situ after its activation into RA(1) or stored as retinyl esters. Using retinol-binding protein knockout model, an alternative way of embryonic retinol supply was described using retinyl esters incorporated into maternal chylomicrons. In the embryo, the principal metabolic event occurring for retin...
Objective. – To evaluate the neonatal morbidity and its risks factors in case of uncomplicated pr... more Objective. – To evaluate the neonatal morbidity and its risks factors in case of uncomplicated preterm rupture of membranes managed conservatively with subsequent planned delivery at 34 weeks of gestation.Patients and methods. – We studied retrospectively 42 consecutive neonates systematically delivered at 34 weeks of gestation after more than 48 hours of conservative management for uncomplicated preterm rupture of membranes. Conservative management was
Objective. – To compare the mode of delivery in two groups of patients selected by their response... more Objective. – To compare the mode of delivery in two groups of patients selected by their response after induction of labour with mifepristone.Patients and methods. – We studied retrospectively 89 cases of labour induction with viable children after 41 weeks of gestation. Bishop scores were less than 6. Patients were given 200 mg of mifepristone per day for 48 h. They were retrospectively divided
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Papers by Vincent Sapin