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1. Chronic endothelial dopamine receptor stimulation improves endothelial function and hemodynamics in autosomal dominant polycystic kidney disease

Author

Dumont, Audrey, Hamzaoui, Mouad, Groussard, Déborah, Iacob, Michèle, Bertrand, Dominique, Remy-Jouet, Isabelle, Hanoy, Mélanie, Le Roy, Frank, Chevalier, Laurence, Enzensperger, Christoph, Arndt, Hans-Dieter, Renet, Sylvanie, Dumesnil, Anaïs, Lévêque, Emilie, Duflot, Thomas, Brunel, Valéry, Michel-Després, Aurore, Audrézet, Marie-Pierre, Richard, Vincent, Joannidès, Robinson, Guerrot, Dominique, and Bellien, Jérémy

Published
2024
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3. Preservation of epoxyeicosatrienoic acid bioavailability prevents renal allograft dysfunction and cardiovascular alterations in kidney transplant recipients

Author

Duflot, Thomas, Laurent, Charlotte, Soudey, Anne, Fonrose, Xavier, Hamzaoui, Mouad, Iacob, Michèle, Bertrand, Dominique, Favre, Julie, Etienne, Isabelle, Roche, Clothilde, Coquerel, David, Le Besnerais, Maëlle, Louhichi, Safa, Tarlet, Tracy, Li, Dongyang, Brunel, Valéry, Morisseau, Christophe, Richard, Vincent, Joannidès, Robinson, Stanke-Labesque, Françoise, Lamoureux, Fabien, Guerrot, Dominique, and Bellien, Jérémy

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Transplantation, Prevention, Cardiovascular, Kidney Disease, Organ Transplantation, Renal and urogenital, Adult, Aged, Allografts, Animals, Biological Availability, Cytochrome P-450 Enzyme System, Disease Models, Animal, Eicosanoids, Epoxide Hydrolases, Epoxy Compounds, Female, Humans, Kidney, Kidney Transplantation, Male, Mice, Mice, 129 Strain, Middle Aged, Reperfusion Injury
Abstract

This study addressed the hypothesis that epoxyeicosatrienoic acids (EETs) synthesized by CYP450 and catabolized by soluble epoxide hydrolase (sEH) are involved in the maintenance of renal allograft function, either directly or through modulation of cardiovascular function. The impact of single nucleotide polymorphisms (SNPs) in the sEH gene EPHX2 and CYP450 on renal and vascular function, plasma levels of EETs and peripheral blood monuclear cell sEH activity was assessed in 79 kidney transplant recipients explored at least one year after transplantation. Additional experiments in a mouse model mimicking the ischemia-reperfusion (I/R) injury suffered by the transplanted kidney evaluated the cardiovascular and renal effects of the sEH inhibitor t-AUCB administered in drinking water (10 mg/l) during 28 days after surgery. There was a long-term protective effect of the sEH SNP rs6558004, which increased EET plasma levels, on renal allograft function and a deleterious effect of K55R, which increased sEH activity. Surprisingly, the loss-of-function CYP2C9*3 was associated with a better renal function without affecting EET levels. R287Q SNP, which decreased sEH activity, was protective against vascular dysfunction while CYP2C8*3 and 2C9*2 loss-of-function SNP, altered endothelial function by reducing flow-induced EET release. In I/R mice, sEH inhibition reduced kidney lesions, prevented cardiac fibrosis and dysfunction as well as preserved endothelial function. The preservation of EET bioavailability may prevent allograft dysfunction and improve cardiovascular disease in kidney transplant recipients. Inhibition of sEH appears thus as a novel therapeutic option but its impact on other epoxyfatty acids should be carefully evaluated.

Published
2021

4. Altered bioavailability of epoxyeicosatrienoic acids is associated with conduit artery endothelial dysfunction in type 2 diabetic patients

Author

Duflot, Thomas, Moreau-Grangé, Lucile, Roche, Clothilde, Iacob, Michèle, Wils, Julien, Rémy-Jouet, Isabelle, Cailleux, Anne-Françoise, Leuillier, Matthieu, Renet, Sylvanie, Li, Dongyang, Morisseau, Christophe, Lamoureux, Fabien, Richard, Vincent, Prévost, Gaëtan, Joannidès, Robinson, and Bellien, Jérémy

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Cardiovascular, Diabetes, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Aged, Biomarkers, Case-Control Studies, Diabetes Mellitus, Type 2, Diabetic Angiopathies, Eicosanoids, Epoxide Hydrolases, Essential Hypertension, Female, Humans, Hyperthermia, Induced, Male, Middle Aged, Nitric Oxide, Nitrites, Nitroglycerin, Radial Artery, Vasodilation, Vasodilator Agents, Type 2 diabetes, Endothelial dysfunction, Soluble epoxide hydrolase, Epoxyeicosatrienoic acids, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

BackgroundThis pathophysiological study addressed the hypothesis that soluble epoxide hydrolase (sEH), which metabolizes the vasodilator and anti-inflammatory epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids (DHETs), contributes to conduit artery endothelial dysfunction in type 2 diabetes.Methods and resultsRadial artery endothelium-dependent flow-mediated dilatation in response to hand skin heating was reduced in essential hypertensive patients (n = 9) and type 2 diabetic subjects with (n = 19) or without hypertension (n = 10) compared to healthy subjects (n = 36), taking into consideration cardiovascular risk factors, flow stimulus and endothelium-independent dilatation to glyceryl trinitrate. Diabetic patients but not non-diabetic hypertensive subjects displayed elevated whole blood reactive oxygen species levels and loss of NO release during heating, assessed by measuring local plasma nitrite variation. Moreover, plasma levels of EET regioisomers increased during heating in healthy subjects, did not change in hypertensive patients and decreased in diabetic patients. Correlation analysis showed in the overall population that the less NO and EETs bioavailability increases during heating, the more flow-mediated dilatation is reduced. The expression and activity of sEH, measured in isolated peripheral blood mononuclear cells, was elevated in diabetic but not hypertensive patients, leading to increased EETs conversion to DHETs. Finally, hyperglycemic and hyperinsulinemic euglycemic clamps induced a decrease in flow-mediated dilatation in healthy subjects and this was associated with an altered EETs release during heating.ConclusionsThese results demonstrate that an increased EETs degradation by sEH and altered NO bioavailability are associated with conduit artery endothelial dysfunction in type 2 diabetic patients independently from their hypertensive status. The hyperinsulinemic and hyperglycemic state in these patients may contribute to these alterations. Trial registration NCT02311075. Registered December 8, 2014.

Published
2019

12. The effect of camelina oil on vascular function in essential hypertensive patients with metabolic syndrome

Author

Bellien, Jeremy, Bozec, Erwan, Bounoure, Frédéric, Khettab, Hakim, Malloizel-Delaunay, Julie, Skiba, Mohamed, Iacob, Michèle, Donnadieu, Nathalie, Coquard, Aude, Morio, Béatrice, Laillet, Brigitte, Rigaudière, Jean-Paul, Chardigny, Jean-Michel, Monteil, Christelle, Vendeville, Cathy, Mercier, Alain, Cailleux, Anne-Françoise, Blanchard, Anne, Amar, Jacques, Fezeu, Léopold, Pannier, Bruno, Bura-Rivière, Alessandra, Boutouyrie, Pierre, Joannidès, Robinson, BOZEC, Erwan, Service de pharmacologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Différenciation et communication neuronale et neuroendocrine (DC2N), Service de pharmacie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Médecine Vasculaire [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Pharmacie [CHU Rouen], Centre de Recherche en Nutrition Humaine Auvergne [CHU Clermont-Ferrand] (CRNH A), Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), UFR Santé, Médecine et Biologie Humaine (UFR SMBH), Université Sorbonne Paris Nord, CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service d'hypertension artérielle et thérapeutique [CHU Toulouse] (HTA et thérapeutique), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Néphrologie [CH Manhès, Fleury-Mérogis], Centre Hospitalier Manhès [Fleury-Mérogis], INSERM UMR_S 970, Team 7 : Cellular, Molecular and Physiological Mechanisms of Heart Failure, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Hôpital Européen Georges Pompidou [APHP] (HEGP)

Subjects
Pathologic, Cyclodextrins, Eicosapentaenoic acid, Camelina oil, Insulin resistance, Vascular function, Metabolic syndrome, Dilatation, Essential hypertension, C-reactive protein, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Cardiovascular system, Plasma, Fluid flow, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Metabolic syndrome x, Hypertension, Lipds, Thiobarbituric acid reactive substances, Endothelium, Alpha-linolenic acid
Abstract

International audience; Background The effects of a dietary supplementation with the vegetable omega-3 α-linolenic acid (ALA) on cardiovascular homeostasis are unclear. In this context, it would be interesting to assess the effects of camelina oil. Objective This study aimed to assess the cardiovascular and metabolic effects of camelina oil in hypertensive patients with metabolic syndrome. Methods In a double-blind placebo-controlled randomized study, treated essential hypertensive patients with metabolic syndrome received during 6 months either cyclodextrin-complexed camelina oil containing ≈ 1.5 g ALA/day (n = 40), or an isocaloric placebo (n = 41), consisting in the same quantity of cyclodextrins and wheat starch. Anthropometric data, plasma lipids, glycemia, insulinemia, creatininemia, thiobarbituric acid reactive substances, high-sensitivity C-reactive protein, and n-3, n-6 and n-9 fatty acids in erythrocyte membranes were measured. Peripheral and central blood pressures, arterial stiffness, carotid intima-media thickness and brachial artery endothelium-dependent flow-mediated dilatation and endothelium-independent dilatation were assessed. Results Compared to placebo, camelina oil increased ALA (mean ± SD: 0 ± 0.04 vs. 0.08 ± 0.06%, P

Published
2022
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13. The effect of camelina oil on vascular function in essential hypertensive patients with metabolic syndrome

Author

Bellien, Jeremy, Bozec, Erwan, Bounoure, Frédéric, Khettab, Hakim, Malloizel-Delaunay, Julie, Skiba, Mohamed, Iacob, Michèle, Donnadieu, Nathalie, Coquard, Aude, Morio, Béatrice, Laillet, Brigitte, Rigaudière, Jean-Paul, Chardigny, Jean-Michel, Monteil, Christelle, Vendeville, Cathy, Mercier, Alain, Cailleux, Anne-Françoise, Blanchard, Anne, Amar, Jacques, Fezeu, Léopold, Pannier, Bruno, Bura-Rivière, Alessandra, Boutouyrie, Pierre, Joannidès, Robinson, Service de pharmacologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Différenciation et communication neuronale et neuroendocrine (DC2N), Service de Pharmacologie, AP-HP, HEGP, Service de Médecine Vasculaire [CHU Toulouse], Centre Hospitalier Régional Universitaire de Toulouse (CHRU Toulouse), Pharmacie [CHU Rouen], Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Clermont Auvergne, CRNH Auvergne, UFR Santé, Médecine et Biologie Humaine (UFR SMBH), Université Sorbonne Paris Nord, Centre d'Investigation Clinique (CIC)-INSERM 1404, CIC - HEGP (CIC 1418), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Department of Arterial Hypertension, Toulouse University III, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Department of Nephrology, Centre Hospitalier F.H. Manhès, Université de Paris, Service de Pharmacologie, INSERM U970, équipe 7, Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de pharmacie [CHU HEGP], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Recherche en Nutrition Humaine Auvergne [CHU Clermont-Ferrand] (CRNH A), Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service d'hypertension artérielle et thérapeutique [CHU Toulouse] (HTA et thérapeutique), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Néphrologie [CH Manhès, Fleury-Mérogis], Centre Hospitalier Manhès [Fleury-Mérogis], Biologie et pharmacologie de l'insuffisence cardiaque = Cellular, Molecular and Physiological Mechanisms of Heart Failure, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Hôpital Européen Georges Pompidou [APHP] (HEGP)

Subjects
Pathologic, Cyclodextrins, Eicosapentaenoic acid, Camelina oil, Insulin resistance, Vascular function, Metabolic syndrome, Dilatation, Essential hypertension, C-reactive protein, Cardiovascular system, Plasma, Fluid flow, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Metabolic syndrome x, Hypertension, Lipds, Thiobarbituric acid reactive substances, Endothelium, Alpha-linolenic acid
Abstract

International audience; Background The effects of a dietary supplementation with the vegetable omega-3 α-linolenic acid (ALA) on cardiovascular homeostasis are unclear. In this context, it would be interesting to assess the effects of camelina oil. Objective This study aimed to assess the cardiovascular and metabolic effects of camelina oil in hypertensive patients with metabolic syndrome. Methods In a double-blind placebo-controlled randomized study, treated essential hypertensive patients with metabolic syndrome received during 6 months either cyclodextrin-complexed camelina oil containing ≈ 1.5 g ALA/day (n = 40), or an isocaloric placebo (n = 41), consisting in the same quantity of cyclodextrins and wheat starch. Anthropometric data, plasma lipids, glycemia, insulinemia, creatininemia, thiobarbituric acid reactive substances, high-sensitivity C-reactive protein, and n-3, n-6 and n-9 fatty acids in erythrocyte membranes were measured. Peripheral and central blood pressures, arterial stiffness, carotid intima-media thickness and brachial artery endothelium-dependent flow-mediated dilatation and endothelium-independent dilatation were assessed. Results Compared to placebo, camelina oil increased ALA (mean ± SD: 0 ± 0.04 vs. 0.08 ± 0.06%, P

Published
2021
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15. Role of Toll-like Receptors 2 and 4 in Mediating Endothelial Dysfunction and Arterial Remodeling in Primary Arterial Antiphospholipid Syndrome

Author

Benhamou, Ygal, Bellien, Jeremy, Armengol, Guillaume, Brakenhielm, Ebba, Adriouch, Sahil, Iacob, Michele, Remy-Jouet, Isabelle, Le Cam-Duchez, Véronique, Monteil, Christelle, Renet, Sylvanie, Jouen, Fabienne, Drouot, Laurent, Menard, Jean-François, Borg, Jeanne-Yvonne, Thuillez, Christian, Boyer, Olivier, Levesque, Hervé, Richard, Vincent, and Joannidès, Robinson

Published
2014
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18. Deleterious impact of a generic temozolomide formulation compared with brand‐name product on the kinetic of platelet concentration and survival in newly diagnosed glioblastoma

Author

Fontanilles, Maxime, primary, Fontanilles, Adeline, additional, Massy, Nathalie, additional, Rouvet, Jean, additional, Pereira, Tony, additional, Alexandru, Cristina, additional, Hanzen, Chantal, additional, Basuyau, Florence, additional, Langlois, Olivier, additional, Clatot, Florian, additional, Tennevet, Isabelle, additional, Di Fiore, Frédéric, additional, Joannidès, Robinson, additional, and Lamoureux, Fabien, additional

Published
2020
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19. Pharmacokinetic modeling of morphine and its glucuronides: Comparison of nebulization versus intravenous route in healthy volunteers.

Author

Duflot, Thomas, Pereira, Tony, Tavolacci, Marie‐Pierre, Joannidès, Robinson, Aubrun, Frédéric, Lamoureux, Fabien, and Lvovschi, Virginie Eve

Subjects
MORPHINE, GLUCURONIDES, PHARMACOKINETICS, BIOAVAILABILITY, VOLUNTEERS, VOLUNTEER service, OPIOIDS
Abstract

Intravenous (i.v.) morphine is a safe, robust, and recommended treatment for severe pain using the titration principle. Despite its high efficacy, it is impacted by organizational constraints related to venous access. Nebulized (NEB) morphine may represent an alternative for titration but pharmacokinetic (PK) properties of short nebulization using routine devices need evaluation. Twenty‐seven healthy volunteers were included to receive NEB or i.v. morphine administration using increasing amounts according to Dixon's reference method. Plasma morphine, morphine‐3‐glucuronide (M3G), and morphine‐6‐glucuronide (M6G) were quantified. PK modeling and simulations were performed using Monolix. Dixon's method exhibited a significantly higher morphine dose regimen in the NEB group versus the i.v. group (6.2 [5.3–7.1] vs. 3.0 [2.0–4.0] mg, p < 0.001). Morphine, M3G, and M6G dose‐normalized exposure were significantly lower in the NEB group versus the i.v. group: morphine (19 [13–23] vs. 1044 [702–1266] µg min/L, p < 0.001), M3G (245 [162–287] vs. 3752 [2487–5165] µg min/L, p < 0.001) and M6G (28 [21–43] vs. 466 [370–723] µg min/L, p < 0.001). The model that best fitted the data consisted in a transit compartment for morphine absorption, three compartments for morphine distribution followed by multiple transit compartments (8.2 and 57.5‐min transit time for M3G and M6G, respectively) and a first order elimination for M3G and M6G. Morphine bioavailability in the NEB group was 3.5% using the i.v. group as reference. Administration route and sex significantly influenced morphine and metabolite PKs. This work aimed to evaluate the PKs of NEB morphine compared with the i.v. route. Despite a bioavailability to improve, NEB morphine administration using a routine device is suitable to plan morphine titration. [ABSTRACT FROM AUTHOR]

Published
2022
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21. Physiological role of endothelin-1 in flow-mediated vasodilatation in humans and impact of cardiovascular risk factors

Author

Bellien, Jérémy, primary, Iacob, Michèle, additional, Monteil, Christelle, additional, Rémy-Jouet, Isabelle, additional, Roche, Clothilde, additional, Duflot, Thomas, additional, Vendeville, Cathy, additional, Gutierrez, Laurence, additional, Thuillez, Christian, additional, Richard, Vincent, additional, and Joannidès, Robinson, additional

Published
2017
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22. Reference values for local arterial stiffness. Part B: femoral artery

Author

Bossuyt, Jelle, Engelen, Lian, Ferreira, Isabel, Stehouwer, Coen, Boutouyrie, Pierre, Laurent, Stéphane, Segers, Patrick, Reesink, Koen, Bortel, Luc Van, Mattace Raso, Francesco US, Hofman, Albert, Franco, Oscar H, Kavousi, Maryam, Rooij, Frank J. A. van, Jouven, Xavier, Empana, Jean Philippe, Bozec, Erwan, Khettab, Hakim, Simon, Tabassome, Pannier, Bruno, Bots, Michiel L., Grobbee, Diederick E., Uiterwaal, Cuno S., Evelein, Annemieke, Graaf, Yolanda van der, Visseren, Frank L. J., Rietzschel, Ernst, Bacquer, Dirk De, Daele, Caroline Van, Buyzere, Marc De, Dekker, Jacqueline, Nijpels, Giel, Twisk, Jos, Smulders, Yvo, Schalkwijk, Casper, Greevenbroek, Marleen van, Kallen, Carla van der, Laar, Roel van de, Feskens, Edith, Staessen, Jan, Thijs, Lutgarde, Kouznetsova, Tatyana, Jin, Yu, Liu, Yanping, Wang, Jiguang, Yan, Li, Bianchini, Elisabetta, Ghiadoni, Lorenzo, Bruno, ROSA MARIA, Pratali, Lorenza, Taddei, Stefano, Fischer, Joachim, Terris, Darcey, Jarczok, Marc, Thole, Maren, Ryliskyte, Ligita, Laucevicius, Aleksandras, Ryliskiene, Kristina, Kuzmickiene, Jurgita, Heuten, Hilde, Goovaerts, Inge, Ennekens, Guy, Vrints, Christiaan, Tolezani, Elaine C, Hong, Valéria, Bortolotto, Luiz, Benetos, Athanase, Labat, Carlos, Lacolley, Patrick, Rimoldi, Stefano F, Stucki, Fabian, Hutter, Damian, Rexhaj, Emrush, Faita, Francesco, Sartori, Claudio, Scherrer, Urs, Allemann, Yves, Giannattasio, Cristina, Nava, Stefano, Maloberti, Alessandro, Meani, Paolo, Vermeer, Cees, Knapen, Marjo, Drummen, Nadja, Kollai, Márk, Pintér, Alexandra, Horváth, Tamás, Thuillez, Christian, Joannidès, Robinson, Bellien, Jérémy, Delahousse, Michel, Karras, Alexandre, Vanmolkot, Floris, Hoon, Jan de, Narkiewicz, Krzysztof, Szyndler, Anna, Hoffmann, Michał, Nowak, Robert, Polonis, Katarzyna, Filipovský, Jan, Agharazii, Mohsen, Briet, Marie, Interne Geneeskunde, MUMC+: MA Interne Geneeskunde (3), Biomedische Technologie, RS: CARIM - R2 - Cardiac function and failure, RS: CARIM - R3 - Vascular biology, and MUMC+: KIO Kemta (9)

Subjects
Adult, Male, Mean arterial pressure, medicine.medical_specialty, Adolescent, Physiology, Population, Femoral artery, Young Adult, Vascular Stiffness, Reference Values, medicine.artery, Internal medicine, Internal Medicine, medicine, 80 and over, risk factors, Humans, education, Pulse wave velocity, Aged, Aged, 80 and over, Aorta, education.field_of_study, business.industry, Middle Aged, medicine.disease, Pulse pressure, Surgery, Femoral Artery, arterial stiffness, ageing, Cardiology, Arterial stiffness, Aortic stiffness, Female, femoral artery, reference values, Cardiology and Cardiovascular Medicine, business
Abstract

OBJECTIVE: Carotid-femoral pulse wave velocity (PWV) is considered the gold standard measure of arterial stiffness, representing mainly aortic stiffness. As compared with the elastic carotid and aorta, the more muscular femoral artery may be differently associated with cardiovascular risk factors (CV-RFs), or, as shown in a recent study, provide additional predictive information beyond carotid-femoral PWV. Still, clinical application is hampered by the absence of reference values. Therefore, our aim was to establish age and sex-specific reference values for femoral stiffness in healthy individuals and to investigate the associations with CV-RFs.METHODS: Femoral artery distensibility coefficient, the inverse of stiffness, was calculated as the ratio of relative diastolic-systolic distension (obtained from ultrasound echo-tracking) and pulse pressure among 5069 individuals (49.5% men, age range: 15-87 years). Individuals without cardiovascular disease (CVD), CV-RFs and medication use (n = 1489; 43% men) constituted a healthy subpopulation used to establish sex-specific equations for percentiles of femoral artery distensibility coefficient across age.RESULTS: In the total population, femoral artery distensibility coefficient Z-scores were independently associated with BMI, mean arterial pressure (MAP) and total to high-density lipoprotein (HDL) cholesterol ratio. Standardized βs, in men and women, respectively, were -0.18 [95% confidence interval (95% CI) -0.23 to -0.13] and -0.19 (-0.23 to -0.14) for BMI; -0.13 (-0.18 to -0.08) and -0.05 (-0.10 to -0.01) for MAP; and -0.07 (-0.11 to -0.02) and -0.16 (-0.20 to -0.11) for total-to-HDL cholesterol ratio.CONCLUSION: In young and middle-aged men and women, normal femoral artery stiffness does not change substantially with age up to the sixth decade. CV-RFs related to metabolic disease are associated with femoral artery stiffness.

Published
2015

23. Reference values for local arterial stiffness. Part A: carotid artery

Author

Engelen, Lian, Bossuyt, Jelle, Ferreira, Isabel, Bortel, Luc Van, Reesink, Koen, Segers, Patrick, Stehouwer, Coen, Laurent, Stéphane, Boutouyrie, Pierre, Mattace Raso, Francesco US, Hofman, Albert, Franco, Oscar H, Kavousi, Maryam, Rooij, Frank J. A. van, Jouven, Xavier, Empana, Jean Philippe, Bozec, Erwan, Khettab, Hakim, Simon, Tabassome, Pannier, Bruno, Bots, Michiel L., Grobbee, Diederick E., Uiterwaal, Cuno S., Evelein, Annemieke, Graaf, Yolanda van der, Visseren, Frank L. J., Rietzschel, Ernst, Bacquer, Dirk De, Daele, Caroline Van, Buyzere, Marc De, Dekker, Jacqueline, Nijpels, Giel, Twisk, Jos, Smulders, Yvo, Schalkwijk, Casper, Greevenbroek, Marleen van, Kallen, Carla van der, Laar, Roel van de, Feskens, Edith, Staessen, Jan, Thijs, Lutgarde, Kouznetsova, Tatyana, Jin, Yu, Liu, Yanping, Wang, Jiguang, Yan, Li, Bianchini, Elisabetta, Ghiadoni, Lorenzo, Bruno, ROSA MARIA, Pratali, Lorenza, Taddei, Stefano, Fischer, Joachim, Terris, Darcey, Jarczok, Marc, Thole, Maren, Ryliskyte, Ligita, Laucevicius, Aleksandras, Ryliskiene, Kristina, Kuzmickiene, Jurgita, Heuten, Hilde, Goovaerts, Inge, Ennekens, Guy, Vrints, Christiaan, Tolezani, Elaine C, Hong, Valéria, Bortolotto, Luiz, Benetos, Athanase, Labat, Carlos, Lacolley, Patrick, Rimoldi, Stefano F, Stucki, Fabian, Hutter, Damian, Rexhaj, Emrush, Faita, Francesco, Sartori, Claudio, Scherrer, Urs, Allemann, Yves, Giannattasio, Cristina, Nava, Stefano, Maloberti, Alessandro, Meani, Paolo, Vermeer, Cees, Knapen, Marjo, Drummen, Nadja, Kollai, Márk, Pintér, Alexandra, Horváth, Tamás, Thuillez, Christian, Joannidès, Robinson, Bellien, Jérémy, Delahousse, Michel, Karras, Alexandre, Vanmolkot, Floris, Hoon, Jan de, Narkiewicz, Krzysztof, Szyndler, Anna, Hoffmann, Michał, Nowak, Robert, Polonis, Katarzyna, Filipovský, Jan, Agharazii, Mohsen, Briet, Marie, Interne Geneeskunde, Biomedische Technologie, MUMC+: MA Interne Geneeskunde (3), RS: CARIM - R2 - Cardiac function and failure, RS: CARIM - R3 - Vascular biology, and MUMC+: KIO Kemta (9)

Subjects
Adult, Male, medicine.medical_specialty, Mean arterial pressure, Adolescent, Physiology, Young Adult, Vascular Stiffness, Reference Values, Internal medicine, medicine.artery, Internal Medicine, medicine, Humans, risk factors, Common carotid artery, Pulse wave velocity, Aged, ageing, arterial stiffness, carotid artery, reference intervals, Aged, 80 and over, business.industry, Middle Aged, medicine.disease, Confidence interval, Pulse pressure, Carotid Arteries, Blood pressure, Intima-media thickness, Cardiology, Arterial stiffness, Female, Cardiology and Cardiovascular Medicine, business
Abstract

Objective:Non-invasive measures of common carotid artery properties, such as diameter and distension, and pulse pressure, have been widely used to determine carotid artery distensibility coefficient - a measure of carotid stiffness (stiffness approximate to 1/distensibility coefficient). Carotid stiffness has been associated with incident cardiovascular disease (CVD) and may therefore be a useful intermediate marker for CVD. We aimed to establish age and sex-specific reference intervals of carotid stiffness.Methods:We combined data on 22708 individuals (age range 15-99 years, 54% men) from 24 research centres worldwide. Individuals without CVD and established cardiovascular risk factors constituted a healthy sub-population (n=3601, 48% men) and were used to establish sex-specific equations for percentiles of carotid distensibility coefficient across age.Results:In the sub-population without CVD and treatment (n=12906, 52% men), carotid distensibility coefficient Z-scores based on these percentile equations were independently and negatively associated, in men and women, respectively, with diabetes {-0.28 [95% confidence interval (CI) -0.41; -0.15] and -0.27 (-0.43; -0.12)}, mean arterial pressure [-0.26 (-0.29; -0.24) and -0.32 (-0.35; -0.29)], total-to-high-density lipoprotein cholesterol ratio [-0.05 (-0.09; -0.02) and -0.05 (-0.11; 0.01)] and BMI [-0.06 (-0.09; -0.04) and -0.05 (-0.08; -0.02)], whereas these were positively associated with smoking [0.30 (0.24; 0.36) and 0.24 (0.18; 0.31)].Conclusions:We estimated age and sex-specific percentiles of carotid stiffness in a healthy population and assessed the association between cardiovascular risk factors and carotid distensibility coefficient Z-scores, which enables comparison of carotid stiffness values between (patient) groups with different cardiovascular risk profiles, helping interpretation of such measures.

Published
2015

24. A sensitive LC-MS/MS method for the quantification of regioisomers of epoxyeicosatrienoic and dihydroxyeicosatrienoic acids in human plasma during endothelial stimulation

Author

Duflot, Thomas, primary, Pereira, Tony, additional, Roche, Clothilde, additional, Iacob, Michèle, additional, Cardinael, Pascal, additional, Hamza, Najla El-Gharbi, additional, Thuillez, Christian, additional, Compagnon, Patricia, additional, Joannidès, Robinson, additional, Lamoureux, Fabien, additional, and Bellien, Jérémy, additional

Published
2016
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25. Polycystin deficiency induces dopamine-reversible alterations in flow-mediated dilatation and vascular nitric oxide release in humans

Author

Lorthioir, Aurélien, primary, Joannidès, Robinson, additional, Rémy-Jouet, Isabelle, additional, Fréguin-Bouilland, Caroline, additional, Iacob, Michèle, additional, Roche, Clothilde, additional, Monteil, Christelle, additional, Lucas, Danièle, additional, Renet, Sylvanie, additional, Audrézet, Marie-Pierre, additional, Godin, Michel, additional, Richard, Vincent, additional, Thuillez, Christian, additional, Guerrot, Dominique, additional, and Bellien, Jérémy, additional

Published
2015
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29. Arterial stiffness is regulated by nitric oxide and endothelium-derived hyperpolarizing factor during changes in blood flow in humans.

Author

Bellien, Jeremy, Favre, Julie, Lacob, Michele, Gao, Ji, Thuillez, Christian, Richard, Vincent, Joannidès, Robinson, Iacob, Michele, and Joannidès, Robinson

Abstract

Cytochrome-derived epoxyeicosatrienoic acids may be important endothelium-derived hyperpolarizing factors, opening calcium-activated potassium channels, but their involvement in the regulation of arterial stiffness during changes in blood flow in humans is unknown. In healthy volunteers, we measured arterial pressure, radial artery diameter, wall thickness, and flow (NIUS02) during hand skin heating in the presence of saline or inhibitors of NO synthase (N(G)-monomethyl-L-arginine), calcium-activated potassium channels (tetraethylammonium), and cytochrome epoxygenases (fluconazole). Arterial compliance and elastic modulus were calculated and fitted as functions of midwall stress to suppress the confounding influence of geometric changes. Under saline infusion, heating induced an upward shift of the compliance-midwall stress curve and a downward shift of the modulus-midwall stress curve demonstrating a decrease in arterial tone and stiffness when blood flow increases. These shifts were reduced by N(G)-monomethyl-L-arginine and abolished by the combinations of N(G)-monomethyl-L-arginine+tetraethylammonium and N(G)-monomethyl arginine+fluconazole. In parallel, in isolated mice coronary arteries, fluconazole and tetraethylammonium reduced the relaxations to acetylcholine. However, fluconazole did not affect the relaxations to the openers of calcium-activated potassium channels of small- and intermediate-conductance NS309 and of large-conductance NS1619 excluding a direct effect on these channels. Moreover, tetraethylammonium reduced the relaxations to NS1619 but not to NS309, suggesting that the endothelium-derived hyperpolarizing factor involved mainly acts on large-conductance calcium-activated potassium channels. These results show in humans that, during flow variations, arterial stiffness is regulated by the endothelium through the release of both NO and cytochrome-related endothelium-derived hyperpolarizing factor. [ABSTRACT FROM AUTHOR]

Published
2010
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30. Protective Effect of Mycophenolate Mofetil on Endothelial Function in an Aortic Allograft Model

Author

Fréguin-Bouilland, Caroline, primary, Godin, Michel, additional, Bellien, Jeremy, additional, Richard, Vincent, additional, Remy-Jouet, Isabelle, additional, Dautreaux, Brigitte, additional, Henry, Jean-Paul, additional, Compagnon, Patricia, additional, Thuillez, Christian, additional, Plissonnier, Didier, additional, and Joannidès, Robinson, additional

Published
2011
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31. Physical determinism in human arterial dynamics

Author

INSA - LESP, Michoux, Nicolas, Joannidès, Robinson, Gouesbet, Gérard, Thuillez, Christian, Maheu, Bruno, Le Sceller, Loïs, INSA - LESP, Michoux, Nicolas, Joannidès, Robinson, Gouesbet, Gérard, Thuillez, Christian, Maheu, Bruno, and Le Sceller, Loïs

Abstract

A successful global vector field reconstruction from physiological signals is obtained for the first time. Data are generated by blood pressure and arterial diameter oscillations by using an arterial catheter with pressure transducer and an ultrasonic echo-tracking system, respectively. Results lead to the unambiguous evidence that such biological systems are characterized by a low-dimensional deterministic dynamical behavior. It is shown that a physiological system can be modelled from the knowledge of its behaviour only, as this has yet been done for theoretical systems and for laboratory designed experiments.

Published
1999

32. Commentaries on Viewpoint: Pick your Poiseuille: Normalizing the shear stimulus in studies of flow-mediated dilation.

Author

Joannidès, Robinson and Bellien, Jérémy

Subjects
LETTERS to the editor, ARTERIAL occlusions, HYPEREMIA, VASCULAR endothelium, NITRIC oxide
Abstract

Several letters to the editor are presented in response to the article "Pick your Poiseuille: Normalizing the shear stimulus in studies of flow-mediated dilation," by B. A. Parker, T. L. Trehearn, and J. R. Meendering in the 2008 issue.

Published
2009
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33. The effect of camelina oil on vascular function in essential hypertensive patients with metabolic syndrome: a randomized, placebo-controlled, double-blind study.

Author

Bellien J, Bozec E, Bounoure F, Khettab H, Malloizel-Delaunay J, Skiba M, Iacob M, Donnadieu N, Coquard A, Morio B, Laillet B, Rigaudière JP, Chardigny JM, Monteil C, Vendeville C, Mercier A, Cailleux AF, Blanchard A, Amar J, Fezeu LK, Pannier B, Bura-Rivière A, Boutouyrie P, and Joannidès R

Subjects
Carotid Intima-Media Thickness, Double-Blind Method, Humans, Fatty Acids, Omega-3 pharmacology, Hypertension drug therapy, Metabolic Syndrome drug therapy
Abstract

Background: The effects of a dietary supplementation with the vegetable ω-3 α-linolenic acid (ALA) on cardiovascular homeostasis are unclear. In this context, it would be interesting to assess the effects of camelina oil., Objective: This study aimed to assess the cardiovascular and metabolic effects of camelina oil in hypertensive patients with metabolic syndrome., Methods: In a double-blind, placebo-controlled randomized study, treated essential hypertensive patients with metabolic syndrome received, during 6 mo, either cyclodextrin-complexed camelina oil containing ≈ 1.5 g ALA/d (n = 40) or an isocaloric placebo (n = 41), consisting of the same quantity of cyclodextrins and wheat starch. Anthropometric data, plasma lipids, glycemia, insulinemia, creatininemia, TBARs, high-sensitivity C-reactive protein, and n-3, n-6, and n-9 fatty acids in erythrocyte membranes were measured. Peripheral and central blood pressures, arterial stiffness, carotid intima-media thickness, and brachial artery endothelium-dependent flow-mediated dilatation (FMD) and endothelium-independent dilatation were assessed., Results: Compared with placebo, camelina oil increased ALA (mean ± SD: 0 ± 0.04 compared with 0.08 ± 0.06%, P <0.001), its elongation product EPA (0 ± 0.5 compared with 0.16 ± 0.65%, P <0.05), and the n-9 gondoic acid (GA; 0 ± 0.04 compared with 0.08 ± 0.04%, P <0.001). No between-group difference was observed for cardiovascular parameters. However, changes in FMD were associated with the magnitude of changes in EPA (r = 0.26, P = 0.03). Compared with placebo, camelina oil increased fasting glycemia (-0.2 ± 0.6 compared with 0.3 ± 0.5 mmol/L, P <0.001) and HOMA-IR index (-0.8 ± 2.5 compared with 0.5 ± 0.9, P <0.01), without affecting plasma lipids, or inflammatory and oxidative stress markers. Changes in HOMA-IR index were correlated with the magnitude of changes in GA (r = 0.32, P <0.01). Nutritional intake remained similar between groups., Conclusion: ALA supplementation with camelina oil did not improve vascular function but adversely affected glucose metabolism in hypertensive patients with metabolic syndrome. Whether this adverse effect on insulin sensitivity is related to GA enrichment, remains to be elucidated., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Published
2022
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34. [Diuretic therapy].

Author

Wils J, Dupuis G, Hemery T, Joannidès R, and Bellien J

Subjects
Drug Therapy, Combination, Humans, Diuretics, Heart Failure
Abstract

Competing Interests: Les auteurs déclarent n’avoir aucun lien d’intérêts.

Published
2019

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