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1. Innovative Therapy Combining Neck Muscle Vibration and Transcranial Direct Current Stimulation in Association with Conventional Rehabilitation in Left Unilateral Spatial Neglect Patients: HEMISTIM Protocol for a Randomized Controlled Trial

Author

Sarah Millot, Jean-Marie Beis, Jonathan Pierret, Marina Badin, Verginia Sabau, Laurent Bensoussan, Jean Paysant, and Hadrien Ceyte

Subjects
neglect, spatial perception, neck muscle vibration, transcranial direct current stimulation, occupational therapy sessions, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Unilateral spatial neglect (USN) rehabilitation requires the development of new methods that can be easily integrated into conventional practice. The aim of the HEMISTIM protocol is to assess immediate and long-term recovery induced by an innovative association of left-side neck-muscle vibration (NMV) and anodal transcranial Direct Current Stimulation (tDCS) on the ipsilesional posterior parietal cortex during occupational therapy sessions in patients with left USN. Participants will be randomly assigned to four groups: control, Left-NMV, Left-NMV + sham-tDCS or Left-NMV + anodal-tDCS. NMV and tDCS will be applied during the first 15 min of occupational therapy sessions, three days a week for three weeks. USN will be assessed at baseline, just at the end of the first experimental session, after the first and third weeks of the protocol and three weeks after its ending. Our primary outcome will be the evolution of the functional Catherine Bergego Scale score. Secondary outcome measures include five tests that investigate different neuropsychological aspects of USN. Left NMV, by activating multisensory integration neuronal networks, might enhance effects obtained by conventional therapy since post-effects were shown when it was combined with upper limb movements. We expect to reinforce lasting intermodal recalibration through LTP-like plasticity induced by anodal tDCS.

Published
2023
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2. Hemolytic anemia repressed hepcidin level without hepatocyte iron overload: lesson from Günther disease model

Author

Sarah Millot, Constance Delaby, Boualem Moulouel, Thibaud Lefebvre, Nathalie Pilard, Nicolas Ducrot, Cécile Ged, Philippe Lettéron, Lucia de Franceschi, Jean Charles Deybach, Carole Beaumont, Laurent Gouya, Hubert De Verneuil, Saïd Lyoumi, Hervé Puy, and Zoubida Karim

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Hemolysis occurring in hematologic diseases is often associated with an iron loading anemia. This iron overload is the result of a massive outflow of hemoglobin into the bloodstream, but the mechanism of hemoglobin handling has not been fully elucidated. Here, in a congenital erythropoietic porphyria mouse model, we evaluate the impact of hemolysis and regenerative anemia on hepcidin synthesis and iron metabolism. Hemolysis was confirmed by a complete drop in haptoglobin, hemopexin and increased plasma lactate dehydrogenase, an increased red blood cell distribution width and osmotic fragility, a reduced half-life of red blood cells, and increased expression of heme oxygenase 1. The erythropoiesis-induced Fam132b was increased, hepcidin mRNA repressed, and transepithelial iron transport in isolated duodenal loops increased. Iron was mostly accumulated in liver and spleen macrophages but transferrin saturation remained within the normal range. The expression levels of hemoglobin-haptoglobin receptor CD163 and hemopexin receptor CD91 were drastically reduced in both liver and spleen, resulting in heme- and hemoglobin-derived iron elimination in urine. In the kidney, the megalin/cubilin endocytic complex, heme oxygenase 1 and the iron exporter ferroportin were induced, which is reminiscent of significant renal handling of hemoglobin-derived iron. Our results highlight ironbound hemoglobin urinary clearance mechanism and strongly suggest that, in addition to the sequestration of iron in macrophages, kidney may play a major role in protecting hepatocytes from iron overload in chronic hemolysis.

Published
2017
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3. Osteomyelitis of the Mandible after Dental Implants in an Immunocompetent Patient

Author

Matthieu Balanger, Margaux Hinet, Christian Vacher, Norbert Bellaiche, Jean-Luc Charrier, and Sarah Millot

Subjects
Dentistry, RK1-715
Abstract

Dental implants are now broadly used to replace missing teeth, and the presence of infectious complications is rising. Dental implant therapy as a local risk factor for the onset of osteomyelitis and its management have not been widely explored. Here, we report an unusual case of mandibular suppurative osteomyelitis caused by Streptococcus intermedius in a healthy and immunocompetent patient secondary to mandibular implants. We describe how surgery combined with systemic application of antibiotics allowed conservation of the dental implants in the mandibular bone, discuss the probable source of contamination, and present the follow-up of the osteomyelitis.

Published
2017
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5. Poor oral health and hygiene habits in patients with infective endocarditis and previously identified predisposing cardiac condition: A prospective cohort study

Author

Vanessa Moby, Sarah Millot, Marie-Line Erpelding, Edouard Euvrard, Geoffrey Bourgeois, Hélène Martin-Thomé, Catherine Chirouze, Pierre Tattevin, Christophe Strady, Nelly Agrinier, Francois Alla, Bernard Iung, Christine Selton-Suty, Bruno Hoen, Xavier Duval, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), 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), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Nanomédecine, imagerie, thérapeutique - UFC (UR 4662) (NIT / NANOMEDECINE), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Polyclinique Courlancy (PC), Polyclinique de Courlancy, Hopital Privé Sévigné [Cesson-Sévigné, France], Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), CHU Pontchaillou [Rennes], ARN régulateurs bactériens et médecine (BRM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Polyclinique Saint André, Laboratoire de Biotechnologie et Microbiologie Appliquée (LBMA), Université Bordeaux Segalen - Bordeaux 2-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Cardiologie [CHRU Nancy], Centre de Recherche Translationnelle - Center for Translational Science (CRT), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by the French Ministry of Health, Société Française de Cardiologie, and Fédération Française de Cardiologie (grant 2009), Inserm XM/GB/2009–051., EI-dents Association pour lȉEtude et la Prévention de l’Endocardite Infectieuse (AEPEI) Study Group, and Jonchère, Laurent

Subjects
Microbiology (medical), Habits, Infectious Diseases, Endocarditis, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, Hygiene, Oral Health, Endocarditis, Bacterial, Prospective Studies, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2022

6. Patients with Obstructive Sleep Apnea and Cardiovascular Diseases: What, When, and Why Is Mandibular Advancement Device Treatment Required? A Short Review

Author

Cindy François, Arthur Bonafé, Camille Roubille, François Roubille, Isabelle Dupuy-Bonafé, Sarah Millot, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and MORNET, Dominique

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], General Medicine
Abstract

International audience; Obstructive sleep apnea is a potentially dangerous condition with significant risks of comorbidities if left untreated. It represents a cardiovascular risk factor in the general population, and a higher prevalence is observed in patients already suffering from cardiovascular diseases. The gold standard treatment, continuous positive airway pressure, is not always accepted or tolerated. The mandibular advancement device represents an alternative treatment that we propose to implement in our study. The objective here is to first present a brief review of the topic. Due to poor evidence in the field, we propose a pilot study to evaluate the effect of a mandibular advancement device in patients with cardiovascular disease who are not treated for their sleep pathology in order to improve their therapeutic management.

Published
2022

7. Prévention de l’endocardite infectieuse

Author

Bernard Iung, Sarah Millot, Sarah Tubiana, Xavier Duval, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, and Université Paris Diderot - Paris 7 (UPD7)

Subjects
medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], media_common.quotation_subject, Dental procedures, MEDLINE, Implant failure, General Medicine, 030204 cardiovascular system & hematology, medicine.disease, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Hygiene, Infective endocarditis, medicine, Endocarditis, 030212 general & internal medicine, Antibiotic prophylaxis, Intensive care medicine, business, Restorative dentistry, media_common
Abstract

Indications of antibiotic prophylaxis are restricted to the patients at highest risk of infective endocarditis undergoing at-risk dental procedures. Guidelines emphasize the importance of daily non-specific oral and cutaneous hygiene. Restorative dentistry, endodontic and periodontal therapy can be performed in patients at high risk of endocarditis, provided careful follow-up is effective. The use of dental implants is no longer contra-indicated in patients at high risk of endocarditis, but the decision be based on an individual analysis of risk factors of implant failure. Evaluations of practices show that prevention of endocarditis is not sufficiently implemented. All health professionals should be aware of the importance of prevention measures of heathcare-associated infective endocarditis. Endocarditis prophylaxis cards are made available to patients and health professionals to make them aware of the endocarditis prophylaxis.

Published
2019

9. Genetic background influences hepcidin response to iron imbalance in a mouse model of hemolytic anemia (Congenital erythropoietic porphyria)

Author

Emmanuel Richard, Pierre Costet, Said Lyoumi, Cécile Ged, Thibaud Lefebvre, Magalie Lalanne, Hervé Puy, Zoubida Karim, Hubert de Verneuil, François Moreau-Gaudry, Isabelle Lamrissi-Garcia, Jean-Marc Blouin, Sarah Millot, Laurent Gouya, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)

Subjects
0301 basic medicine, Hemolytic anemia, Male, medicine.medical_specialty, Iron Overload, Porphyrins, Anemia, Iron, Porphyria, Erythropoietic, Ferroportin, Biophysics, Congenic, Congenital erythropoietic porphyria, Mice, Inbred Strains, Biochemistry, Hemolysis, 03 medical and health sciences, 0302 clinical medicine, Hepcidins, Hepcidin, hemic and lymphatic diseases, Internal medicine, medicine, Animals, Molecular Biology, Cation Transport Proteins, ComputingMilieux_MISCELLANEOUS, Mice, Inbred BALB C, biology, business.industry, Cell Biology, medicine.disease, Uroporphyrinogen III Synthetase, 3. Good health, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, Endocrinology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, 030220 oncology & carcinogenesis, biology.protein, Erythropoiesis, Female, business
Abstract

Clinical severity is heterogeneous among patients suffering from congenital erythropoietic porphyria (CEP) suggesting a modulation of the disease (UROS deficiency) by environmental factors and modifier genes. A KI model of CEP due to a missense mutation of UROS gene present in human has been developed on 3 congenic mouse strains (BALB/c, C57BL/6, and 129/Sv) in order to study the impact of genetic background on disease severity. To detect putative modifiers of disease expression in congenic mice, hematologic data, iron parameters, porphyrin content and tissue samples were collected. Regenerative hemolytic anemia, a consequence of porphyrin excess in RBCs, had various expressions: 129/Sv mice were more hemolytic, BALB/c had more regenerative response to anemia, C57BL/6 were less affected. Iron status and hemolysis level were directly related: C57BL/6 and BALB/c had moderate hemolysis and active erythropoiesis able to reduce iron overload in the liver, while, 129/Sv showed an imbalance between iron release due to hemolysis and erythroid use. The negative control of hepcidin on the ferroportin iron exporter appeared strain specific in the CEP mice models tested. Full repression of hepcidin was observed in BALB/c and 129/Sv mice, favoring parenchymal iron overload in the liver. Unchanged hepcidin levels in C57BL/6 resulted in retention of iron predominantly in reticuloendothelial tissues. These findings open the field for potential therapeutic applications in the human disease, of hepcidin agonists and iron depletion in chronic hemolytic anemia.

Published
2019

10. [Prevention of Infective endocarditis]

Author

Xavier, Duval, Sarah, Millot, Sarah, Tubiana, and Bernard, Iung

Subjects
Practice Guidelines as Topic, Humans, Endocarditis, Bacterial
Abstract

Indications of antibiotic prophylaxis are restricted to the patients at highest risk of infective endocarditis undergoing at-risk dental procedures. Guidelines emphasize the importance of daily non-specific oral and cutaneous hygiene. Restorative dentistry, endodontic and periodontal therapy can be performed in patients at high risk of endocarditis, provided careful follow-up is effective. The use of dental implants is no longer contra-indicated in patients at high risk of endocarditis, but the decision be based on an individual analysis of risk factors of implant failure. Evaluations of practices show that prevention of endocarditis is not sufficiently implemented. All health professionals should be aware of the importance of prevention measures of heathcare-associated infective endocarditis. Endocarditis prophylaxis cards are made available to patients and health professionals to make them aware of the endocarditis prophylaxis.

Published
2019

11. Reply to Raoult

Author

Sarah Millot, Bruno Hoen, François Alla, Christine Selton-Suty, D Thomas, Christophe Strady, Vanessa Moby, Pierre Tattevin, Nelly Agrinier, Catherine Chirouze, Edouard Euvrard, Xavier Duval, CIC Hôpital Bichat, AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-UFR de Médecine, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'Odontologie [CHRU Nancy], Service des maladies infectieuses et réanimation médicale, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Médecine Interne, Infectiologie et Pathologie des voyages, Polyclinique Saint André, Centre d'Investigation Clinique CIC-1431, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), CIC 1433 Epidémiologie clinique, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Institut National de la Santé et de la Recherche Médicale ( INSERM ) -UFR de Médecine-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre de recherche sur l'inflamation - UMR 1149, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Centre d'Investigation Clinique Antilles-Guyane ( CIC - Antilles Guyane ), CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université des Antilles et de la Guyane ( UAG ), Institut National de la Santé et de la Recherche Médicale (INSERM)-UFR de Médecine-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Service des maladies infectieuses et réanimation médicale [Rennes] = Infectious Disease and Intensive Care [Rennes], CHU Pontchaillou [Rennes], Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), 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)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles et de la Guyane (UAG), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-UFR de Médecine, Laboratoire Chrono-environnement (UMR 6249) (LCE), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), 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), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)

Subjects
Microbiology (medical), medicine.medical_specialty, media_common.quotation_subject, [SDV]Life Sciences [q-bio], MEDLINE, Raoult's law, 01 natural sciences, Oral hygiene, Habits, 03 medical and health sciences, 0302 clinical medicine, Hygiene, Humans, Medicine, 030212 general & internal medicine, 0101 mathematics, ComputingMilieux_MISCELLANEOUS, media_common, Endocarditis, [ SDV ] Life Sciences [q-bio], business.industry, 010102 general mathematics, Oral Hygiene, Infectious Diseases, Case-Control Studies, Family medicine, Immunology, business
Abstract

International audience

Published
2017

12. Oral streptococcal endocarditis, oral hygiene habits and recent dental procedures: a case-control study

Author

Bruno Hoen, Sarah Millot, Alla François, D Thomas, Edouard Euvrard, Vanessa Moby, Catherine Chirouze, Christine Selton-Suty, Xavier Duval, Pierre Tattevin, Christophe Strady, Nelly Agrinier, CIC1425 - Bichat [AP-HP Hôpital Bichat - Claude Bernard], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), UFR médecine - Bichat, Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service des maladies infectieuses et tropicales, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques, Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Service d'Odontologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service des maladies infectieuses et réanimation médicale [Rennes] = Infectious Disease and Intensive Care [Rennes], CHU Pontchaillou [Rennes], Polyclinique de Courlancy, Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), 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), Institut de cardiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'investigation clinique Antilles-Guyane (CIC - Antilles Guyane), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de la Martinique [Fort de France]-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Service des Maladies Infectieuses et Tropicales[Point-à-Pitre], CHU Pointe-à-Pitre/Abymes [Guadeloupe], Maladies infectieuses et tropicales dans la Caraïbe (MAITC EA 4537), CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de la Martinique [Fort de France]-Université des Antilles (UA), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), French ministry of Health, Société Française de Cardiologie and Fédération Française de Cardiologie (grant 2009), Inserm XM/GB/2009-051, AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), Université Paris Diderot - Paris 7 ( UPD7 ) -PRES Sorbonne Paris Cité, Infection, Antimicrobiens, Modélisation, Evolution ( IAME ), Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris 13 ( UP13 ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de recherche sur l'inflamation - UMR 1149, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire Chrono-environnement - UFC (UMR 6249) ( LCE ), Université Bourgogne Franche-Comté [COMUE] ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques, Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Service des maladies infectieuses et réanimation médicale, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou, Centre d'Investigation Clinique CIC-1431, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), CIC-Nancy, Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Centre d'investigation clinique Antilles-Guyane ( CIC - Antilles Guyane ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU de la Martinique-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Maladies infectieuses et tropicales dans la Caraïbe ( MITC ), CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles ( UA ) -CHU de la Martinique, Université de Lorraine ( UL ), Maladies chroniques, santé perçue, et processus d'adaptation ( APEMAC ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Saint-Jacques, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy]-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU de la Martinique [Fort de France]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Maladies infectieuses et tropicales dans la Caraïbe (MAITC), Université de Lorraine (UL), Centre d'Investigation Clinique Antilles Guyane, Inserm CIC1424, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-CHU de la Martinique [Fort de France], Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques, Université Paris Diderot - Paris 7 (UPD7) - Institut National de la Santé et de la Recherche Médicale (INSERM), INSERA CIC, Hôpital Bichat - Claude Bernard, Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Bichat - Claude Bernard [Paris] - Université Paris Diderot - Paris 7 (UPD7) - Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Bichat - Claude Bernard [Paris] - Université Paris Diderot - Paris 7 (UPD7), Laboratoire Ressources halieutiques, Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER), Laboratoire Chrono-environnement (LCE), Université Bourgogne Franche-Comté (UBFC) - Centre National de la Recherche Scientifique (CNRS) - Université de Franche-Comté (UFC), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon) - Hôpital Saint-Jacques, Université de Lorraine (UL) - Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 (UR1) - Hôpital Pontchaillou, CHU Reims, Service d'épidémiologie et évaluation clinique (CHRU Nancy), Institut des Nanotechnologies de Lyon - Site de l'INSA (INL), École Centrale de Lyon (ECL) - Université Claude Bernard Lyon 1 (UCBL) - Institut National des Sciences Appliquées de Lyon (INSA Lyon) - Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG) - Institut National de la Santé et de la Recherche Médicale (INSERM) - CHU de Pointe-à-Pitre - Centre Hospitalier de Cayenne Andrée Rosemon - CHU de Fort de France, Maladies chroniques, santé perçue, et processus d'adaptation. (APEMAC), Université Paris Descartes - Paris 5 (UPD5) - Université de Lorraine (UL), and Centre d'Investigation Clinique - Innovation Technologique [CHRU Nancy] (CIC-IT)

Subjects
Microbiology (medical), media_common.quotation_subject, case-control study, Dentistry, Physical examination, 030204 cardiovascular system & hematology, Oral hygiene, Article, 03 medical and health sciences, hygiene, 0302 clinical medicine, Hygiene, medicine, Endocarditis, 030212 general & internal medicine, media_common, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, medicine.diagnostic_test, business.industry, Calculus (dental), dental status, Case-control study, Interdental consonant, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, medicine.disease, 3. Good health, stomatognathic diseases, Infectious Diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Infective endocarditis, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, prophylaxis, business
Abstract

International audience; AIMS:To compare oral hygiene habits, oro-dental status, and dental procedures in patients with infective endocarditis (IE) according to whether the IE-causing microorganism originated in the oral cavity.METHODS:We conducted an assessor-blinded case-control study in 6 French tertiary-care hospitals. Oral hygiene habits were recorded using a self-administered questionnaire. Oro-dental status was analysed by trained dental practitioners blinded to the microorganism, using standardized clinical examination and dental panoramic tomography. History of dental procedures was obtained through patient and dentist interviews. Microorganisms were categorised as oral streptococci or non-oral pathogens using an expert-validated list kept confidential during the course of the study. Cases and controls had definite IE caused either by oral streptococci or non-oral pathogens, respectively. Participants were enrolled between May 2008 and January 2013.RESULTS:Cases (n=73) were more likely than controls (n=192) to be aged < 65 years (OR: 2.85; 95% CI 1.41-5.76), to be female (OR: 2.62; 95% CI 1.20-5.74), to have native valve disease (OR: 2.44; 95% CI: 1.16-5.13), to use toothpicks, dental water jet, interdental brush and/or flossing (OR: 3.48; 95% CI: 1.30-9.32), and to have had dental procedures during the prior three months (OR: 3.31; 95% CI: 1.18-9.29), while they were less likely to brush teeth after meals. Gingival inflammation, calculus and infectious dental diseases were not significantly different between groups.CONCLUSIONS:Patients with IE caused by oral streptococci differ from patients with IE caused by non-oral pathogens regarding background characteristics, oral hygiene habits, and recent dental procedures, but not current oro-dental status.

Published
2017

13. Osteomyelitis of the Mandible after Dental Implants in an Immunocompetent Patient

Author

Sarah Millot, Matthieu Balanger, Margaux Hinet, Christian Vacher, J L Charrier, and Norbert Bellaiche

Subjects
medicine.medical_specialty, Unusual case, biology, business.industry, Osteomyelitis, medicine.medical_treatment, Mandible, Dentistry, Case Report, RK1-715, 030206 dentistry, Streptococcus intermedius, biology.organism_classification, medicine.disease, Surgery, 03 medical and health sciences, stomatognathic diseases, 0302 clinical medicine, stomatognathic system, Medicine, 030212 general & internal medicine, business, Dental implant, General Dentistry
Abstract

Dental implants are now broadly used to replace missing teeth, and the presence of infectious complications is rising. Dental implant therapy as a local risk factor for the onset of osteomyelitis and its management have not been widely explored. Here, we report an unusual case of mandibular suppurative osteomyelitis caused by Streptococcus intermedius in a healthy and immunocompetent patient secondary to mandibular implants. We describe how surgery combined with systemic application of antibiotics allowed conservation of the dental implants in the mandibular bone, discuss the probable source of contamination, and present the follow-up of the osteomyelitis.

Published
2017

14. Position paper for the evaluation and management of oral status in patients with valvular disease: Groupe de Travail Valvulopathies de la Societe Francaise de Cardiologie, Societe Frangaise de Chinirgie Orale, Societe Frangaise de Parodontologie et d'Implantologie Orale, Societe Frangaise d'Endodontie et Societe de Pathologie Infectieuse de Langue Frangaise

Author

Philippe Lesclous, Sarah Millot, Marie-Laure Colombier, Philippe Tramba, Bernard Iung, Emmanuel Lansac, Clement Messeca, Mathieu Ballanger, Jean Luc Charrier, Christophe Tribouilloy, Xavier Duval, Fabien Doguet, Loredana Radoï, Stéphane Simon, Alain Berrebi, Gilbert Habib, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'ingénierie osteo-articulaire et dentaire (LIOAD), Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Nantes - UFR Odontologie, Université de Nantes (UN), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Regenerative Medicine and Skeleton research lab (RMeS), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Université Paris Descartes - Faculté de Chirurgie Dentaire (UPD5 Odontologie), Université Paris Descartes - Paris 5 (UPD5), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Oral medicine and oral surgery department, Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Laboratoire Hospitalier et Universitaire Parasitologie Mycologie, Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Gynécologie‑Obstétrique, Hôpital Paule de Viguier, Service de chirurgie cadiovasculaire et thoracique [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Cardiologie [Amiens], CHU Amiens-Picardie, Mécanismes physiologiques et conséquences des calcifications cardiovasculaires: rôle des remodelages cardiovasculaires et osseux, Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), CIC Hôpital Bichat, AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-UFR de Médecine, DHU FIRE Centre de compétence des maladies pulmonaires rares, Service de cardiologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Institut National de la Santé et de la Recherche Médicale (INSERM)-UFR de Médecine-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Nantes - UFR Odontologie (UFR Odonto), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Regenerative Medicine and Skeleton (RMeS), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Gynécologie [CHU Toulouse], Pôle Femme-Mère-Couple [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), AP-HP - Hôpital Bichat - Claude Bernard [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-UFR de Médecine

Subjects
medicine.medical_specialty, medicine.diagnostic_test, business.industry, General surgery, valvular heart disease, Implant failure, Physical examination, 030206 dentistry, General Medicine, Disease, 030204 cardiovascular system & hematology, medicine.disease, 3. Good health, Surgery, 03 medical and health sciences, 0302 clinical medicine, Acute Endocarditis, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Infective endocarditis, medicine, Endocarditis, Antibiotic prophylaxis, Cardiology and Cardiovascular Medicine, business
Abstract

International audience; Oral health is of particular importance in patients with heart valve diseases because of the risk of infective endocarditis. Recommendations for antibiotic prophylaxis before dental procedures have been restricted, but the modalities of oral evaluation and dental care are not detailed in guidelines. Therefore, a multidisciplinary working group reviewed the literature to propose detailed approaches for the evaluation and management of buccodental status in patients with valvular disease. Simple questions asked by a non-dental specialist may draw attention to buccodental diseases. Besides clinical examination, recent imaging techniques are highly sensitive for the detection of inflammatory bone destruction directly related to oral or dental infection foci. The management of buccodental disease before cardiac valvular surgery should be adapted to the timing of the intervention. Simple therapeutic principles can be applied even before urgent intervention. Restorative dentistry and endodontic and periodontal therapy can be performed before elective valvular intervention and during the follow-up of patients at high risk of endocarditis. The detection and treatment of buccodental foci of infection should follow specific rules in patients who present with acute endocarditis. Implant placement is no longer contraindicated in patients at intermediate risk of endocarditis, and can also be performed in selected high-risk patients. The decision for implant placement should follow an analysis of general and local factors increasing the risk of implant failure. The surgical and prosthetic procedures should be performed in optimal safety conditions. It is therefore now possible to safely decrease the number of contraindicated dental procedures in patients at risk of endocarditis. (C) 2017 Elsevier Masson SAS. All rights reserved.

Published
2017

16. Hemolytic anemia repressed hepcidin level without hepatocyte iron overload: lesson from Günther disease model

Author

Sarah, Millot, Constance, Delaby, Boualem, Moulouel, Thibaud, Lefebvre, Nathalie, Pilard, Nicolas, Ducrot, Cécile, Ged, Philippe, Lettéron, Lucia, de Franceschi, Jean Charles, Deybach, Carole, Beaumont, Laurent, Gouya, Hubert, De Verneuil, Saïd, Lyoumi, Hervé, Puy, and Zoubida, Karim

Subjects
Mice, Knockout, Anemia, Hemolytic, Erythrocytes, Iron Overload, Iron, Macrophages, Gene Expression, Apoptosis, Biological Transport, Mice, Transgenic, Heme, Articles, Disease Models, Animal, Mice, Hepcidins, Stress, Physiological, Hepatocytes, Animals, Humans, Erythropoiesis, Biomarkers, Spleen
Abstract

Hemolysis occurring in hematologic diseases is often associated with an iron loading anemia. This iron overload is the result of a massive outflow of hemoglobin into the bloodstream, but the mechanism of hemoglobin handling has not been fully elucidated. Here, in a congenital erythropoietic porphyria mouse model, we evaluate the impact of hemolysis and regenerative anemia on hepcidin synthesis and iron metabolism. Hemolysis was confirmed by a complete drop in haptoglobin, hemopexin and increased plasma lactate dehydrogenase, an increased red blood cell distribution width and osmotic fragility, a reduced half-life of red blood cells, and increased expression of heme oxygenase 1. The erythropoiesis-induced Fam132b was increased, hepcidin mRNA repressed, and transepithelial iron transport in isolated duodenal loops increased. Iron was mostly accumulated in liver and spleen macrophages but transferrin saturation remained within the normal range. The expression levels of hemoglobin-haptoglobin receptor CD163 and hemopexin receptor CD91 were drastically reduced in both liver and spleen, resulting in heme- and hemoglobin-derived iron elimination in urine. In the kidney, the megalin/cubilin endocytic complex, heme oxygenase 1 and the iron exporter ferroportin were induced, which is reminiscent of significant renal handling of hemoglobin-derived iron. Our results highlight ironbound hemoglobin urinary clearance mechanism and strongly suggest that, in addition to the sequestration of iron in macrophages, kidney may play a major role in protecting hepatocytes from iron overload in chronic hemolysis.

Published
2016

17. Bêta-thalassémie majeure : actualisation de la prise en charge en médecine bucco-dentaire

Author

Henri Woimant, Anne-Laure Ejeil, Sarah Millot, and J L Charrier

Subjects
Gynecology, medicine.medical_specialty, business.industry, medicine, Periodontics, Dentistry (miscellaneous), Oral Surgery, Oral cavity, business
Abstract

La β -thalassemie majeure represente un syndrome genetique qui s’accompagne d’un defaut de synthese de l’hemoglobine et entraine une anemie severe. Malgre des progres importants dans la prise en charge des patients, il existe toujours de nombreuses complications dues a la maladie elle-meme, aux transfusions repetees, a la surcharge en fer et a la toxicite des chelateurs du fer; elles dominent encore le pronostic vital. Toutes ces complications et/ou leurs traitements ont un impact sur la prise en charge bucco-dentaire des patients; le cas rapporte en constitue un exemple. Tout praticien peut rencontrer dans sa pratique un patient atteint d’une β -thalassemie majeure : il est indispensable de connaitre les mesures particulieres qui doivent etre prises lors de l’anamnese, de l’examen clinique, des interventions chirurgicales et de la surveillance postoperatoire.

Published
2011

18. Erythropoietin stimulates spleen BMP4-dependent stress erythropoiesis and partially corrects anemia in a mouse model of generalized inflammation

Author

Valérie Andrieu, Sarah Millot, Carole Beaumont, Zoubida Karim, Margarita Hurtado-Nedelec, Said Lyoumi, Philippe Lettéron, Sigismond Lasocki, Samira Bennada, J L Charrier, and Olivier Thibaudeau

Subjects
Male, medicine.medical_specialty, Anemia, Blotting, Western, Immunology, Apoptosis, Spleen, Bone Morphogenetic Protein 4, Biochemistry, Mice, chemistry.chemical_compound, Bone Marrow, Erythroblast, hemic and lymphatic diseases, Internal medicine, Receptors, Erythropoietin, medicine, Animals, Humans, Erythropoiesis, RNA, Messenger, Erythropoietin, Erythroid Precursor Cells, Inflammation, Reverse Transcriptase Polymerase Chain Reaction, business.industry, Zymosan, Cell Biology, Hematology, medicine.disease, Recombinant Proteins, Mice, Inbred C57BL, Disease Models, Animal, Red blood cell, Haematopoiesis, medicine.anatomical_structure, Endocrinology, chemistry, business, Signal Transduction, medicine.drug
Abstract

Mouse bone marrow erythropoiesis is homeostatic, whereas after acute anemia, bone morphogenetic protein 4 (BMP4)–dependent stress erythropoiesis develops in the spleen. The aim of this work was to compare spleen stress erythropoiesis and bone marrow erythropoiesis in a mouse model of zymosan-induced generalized inflammation, which induces long-lasting anemia and to evaluate the ability of erythropoietin (Epo) injections to correct anemia in this setting. The effects of zymosan and/or Epo injections on erythroid precursor maturation and apoptosis, serum interferon-γ levels, hematologic parameters, and spleen BMP4 expression were analyzed, as well as the effect of zymosan on red blood cell half-life. We found that bone marrow erythropoiesis is suppressed by inflammation and does not respond to Epo administration, despite repression of erythroblast apoptosis. On the contrary, a robust erythropoietic response takes place in the spleen after Epo injections in both control and zymosan-induced generalized inflammation mice. This specific response implies Epo-mediated induction of BMP4 expression by F4/80+ spleen macrophages, proliferation of stress burst-forming units-erythroid, and increased number of spleen erythroblasts. It allows only partial recovery of anemia, probably because of peripheral destruction of mature red cells. It is not clear whether similar BMP4-dependent stress erythropoiesis can occur in human bone marrow after Epo injections.

Published
2010

19. Anémie en réanimation: physiopathologie et pistes thérapeutiques

Author

Philippe Montravers, Carole Beaumont, Sarah Millot, and S. Lasocki

Subjects
Hematology
Abstract

L’anemie est tres frequente chez les patients hospitalises dans les services de reanimation et la mise en place d’une politique transfusionnelle restrictive aboutit a la presence d’une anemie chez 80 a 90 % des patients au sortir de la reanimation. Les consequences sur la survie ou la recuperation peuvent etre tres nefastes. L’anemie de ces patients est multifactorielle, resultant, d’une part, d’un etat inflammatoire et, d’autre part, de pertes et/ou de prelevements de sang importants evalues a 128 mL/j representant une perte en fer-element de 64 mg/j. Plusieurs mecanismes contribuent a l’anemie des etats inflammatoires, en particulier une alteration de la proliferation des precurseurs erythroides, une diminution de la synthese d’erythropoietine (EPO) par le rein, une activation des macrophages, conduisant a une augmentation de l’erythrophagocytose et a une diminution de la duree de vie des globules rouges, et enfin des perturbations de l’homeostasie du fer. En particulier, l’IL6 stimule fortement l’expression de l’hepcidine qui reprime le recyclage du fer heminique au niveau des macrophages et induit une diminution du fer serique. La plupart de ces mecanismes ont ete mis en evidence chez les patients de reanimation a l’exception de l’augmentation de l’hepcidine qui n’a jamais ete exploree dans ce contexte. Par ailleurs, les pertes sanguines repetees sont susceptibles d’entrainer une carence en fer vraie, alors que l’inflammation entraine une diminution de la disponibilite du fer pour l’erythropoiese par sequestration dans les macrophages. La stimulation de l’erythropoiese reprime la synthese d’hepcidine, et des travaux recents obtenus sur un modele murin de l’anemie de reanimation suggerent que l’EPO ou les prelevements sanguins iteratifs peuvent reprimer l’hepcidine, meme en presence de taux eleves d’IL6. Ces resultats incitent a developper des etudes cliniques pour evaluer le benefice d’un traitement de l’anemie de reanimation par des injections d’EPO, avec ou non une supplementation en fer, dans l’idee, non plus de limiter les transfusions, mais plutot de corriger l’anemie a long terme et d’ameliorer l’avenir des patients.

Published
2009

20. Hepcidin as a Major Component of Renal Antibacterial Defenses against Uropathogenic Escherichia coli

Author

Dounia Houamel, Philippe Lettéron, Hervé Puy, Alain Vandewalle, Sarah Millot, Marie-Agnès Sari, Erick Denamur, Sophie Vaulont, Said Lyoumi, Carole Beaumont, Thibaud Lefebvre, Zoubida Karim, Boualem Moulouel, Nicolas Ducrot, Raed Daher, Odile Bouvet, Jerome Tourret, and Laurent Gouya

Subjects
0301 basic medicine, inorganic chemicals, STAT3 Transcription Factor, congenital, hereditary, and neonatal diseases and abnormalities, Neutrophils, Iron, Colony Count, Microbial, Smad Proteins, SMAD, Biology, medicine.disease_cause, urologic and male genital diseases, Microbiology, 03 medical and health sciences, Mice, Anti-Infective Agents, Hepcidins, In vivo, Hepcidin, hemic and lymphatic diseases, Renal medulla, medicine, Escherichia coli, Animals, RNA, Messenger, Phosphorylation, Cells, Cultured, Escherichia coli Infections, Mice, Knockout, Kidney, Kidney Medulla, Nephritis, Kinase, nutritional and metabolic diseases, General Medicine, In vitro, Bacterial Load, 030104 developmental biology, medicine.anatomical_structure, Basic Research, Nephrology, Urinary Tract Infections, biology.protein, Mice, Inbred CBA, Cytokines, Female, Signal Transduction
Abstract

The iron-regulatory peptide hepcidin exhibits antimicrobial activity. Having previously shown hepcidin expression in the kidney, we addressed its role in urinary tract infection (UTI), which remains largely unknown. Experimental UTI was induced in wild-type (WT) and hepcidin-knockout (Hepc-/-) mice using the uropathogenic Escherichia coli CFT073 strain. Compared with infected WT mice, infected Hepc-/- mice showed a dramatic increase in renal bacterial load. Moreover, bacterial invasion was significantly dampened by the pretreatment of WT mice with hepcidin. Infected Hepc-/- mice exhibited decreased iron accumulation in the renal medulla and significant attenuation of the renal inflammatory response. Notably, we demonstrated in vitro bacteriostatic activity of hepcidin against CFT073. Furthermore, CFT073 repressed renal hepcidin, both in vivo and in cultured renal cells, and reduced phosphorylation of SMAD kinase in vivo, suggesting a bacterial strategy to escape the antimicrobial activities of hepcidin. In conclusion, we provide new mechanisms by which hepcidin contributes to renal host defense and suggest that targeting hepcidin offers a strategy to prevent bacterial invasion.

Published
2015

22. Efficacy and toxicity of intravenous iron in a mouse model of critical care anemia*

Author

Nicholas Heming, Sigismond Lasocki, Erick Denamur, Philippe Montravers, Carole Beaumont, Philippe Lettéron, Jérôme Tourret, Fathi Driss, Sarah Millot, Jamel El Benna, Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), and Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Spleen/chemistry, Superoxide Dismutase/genetics/metabolism, Maltose/administration and dosage/analogs and derivatives/toxicity, Luminescence, Catalase/genetics/metabolism, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Messenger/metabolism, Trace Elements/administration and dosage, 030204 cardiovascular system & hematology, Pharmacology, Critical Care and Intensive Care Medicine, medicine.disease_cause, Inbred C57BL, Ferric Compounds, Anemia/drug therapy, chemistry.chemical_compound, Hemoglobins, Mice, Random Allocation, 0302 clinical medicine, Phlebotomy, 030202 anesthesiology, biology, Hematinics/administration and dosage/toxicity, Anemia, Iron deficiency, Zymosan/pharmacology, Catalase, 3. Good health, Liver/chemistry/metabolism, Reactive Oxygen Species/blood, Liver, Toxicity, Injections, Intravenous, Antimicrobial Cationic Peptides/genetics/metabolism, Intravenous, Iron/administration and dosage/analysis, Inflammation/chemically induced, Ferric Compounds/administration and dosage/toxicity, Iron, Intraperitoneal injection, Sepsis/drug therapy, Injections, Sepsis, 03 medical and health sciences, Hepcidins, Hepcidin, medicine, Animals, RNA, Messenger, Maltose, Inflammation, business.industry, Animal, Superoxide Dismutase, Zymosan, medicine.disease, Diet, Trace Elements, Mice, Inbred C57BL, Disease Models, Animal, chemistry, Immunology, Disease Models, biology.protein, Hematinics, RNA, business, Reactive Oxygen Species, Oxidative stress, Spleen, Antimicrobial Cationic Peptides
Abstract

International audience; OBJECTIVE: Anemia is common in critically ill patients, due to inflammation and blood loss. Anemia can be associated with iron deficiency and low serum hepcidin levels. However, iron administration in this setting remains controversial because of its potential toxicity, including oxidative stress induction and sepsis facilitation. The objective of this work was to determine the efficacy and toxicity of iron administration using a mouse model mimicking critical care anemia as well as a model of acute septicemia. DESIGN: Prospective, randomized, open label controlled animal study. SETTING: University-based research laboratory. SUBJECTS: C57BL/6 and OF1 mice. INTERVENTIONS: Intraperitoneal injection of zymosan inducing generalized inflammation in C57BL/6 mice, followed in our full model by repeated phlebotomies. A dose equivalent to 15 mg/kg of ferric carboxymaltose was injected intravenously on day 5. To assess the toxicity of iron in a septicemia model, OF1 mice were simultaneously injected with iron and different Escherichia coli strains. MEASUREMENTS AND MAIN RESULTS: To investigate the effect of iron on oxidative stress, we measured reactive oxygen species production in the blood using luminol-amplified chemiluminescence and superoxide dismutase 2 messenger RNA levels in the liver. These markers of oxidative stress were increased after iron administration in control mice but not in zymosan-treated mice. Liver catalase messenger RNA levels decreased in iron-treated control mice. Iron administration was not associated with increased mortality in the septicemia model or in the generalized inflammation model. Iron increased hemoglobin levels in mice fed with a low iron diet and subjected to phlebotomies and zymosan 2 wks after treatment administration. CONCLUSIONS: Adverse effects of intravenous iron supplementation by ferric carboxymaltose seem to be minimal in our animal models. Furthermore, iron appears to be effective in correcting anemia, despite inflammation. Studies of efficacy and safety of iron in critically ill patients are warranted.

Published
2012

23. Protoporphyrin retention in hepatocytes and kupffer cells prevents sclerosing cholangitis in erythropoietic protoporphyria mouse model

Author

Jean Charles Deybach, Vincent Oustric, Said Lyoumi, Nicholas Heming, Raoul Poupon, Sarah Millot, Philippe Lettéron, Dominique Rainteau, Marie Abitbol, Gilles Berdeaux, Zoubida Karim, Xavier Montagutelli, Laurent Guillmot, Carole Beaumont, Florence Bernex, Hervé Puy, Laurent Gouya, Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Français des Porphyries, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Génétique Moléculaire et Cellulaire (UGMC), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Trafic Membranaire et Signalisation Dans les Cellules Epitheliales, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de Recherche Saint-Antoine (UMRS893), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Funding Supported by grants from the Public Health and Consumer Protection Directorate (DG SANCO), PHEA programme from the European Commission, Brussels, Belgium ('European Porphyria Network'), and grant ANR-07-MRAR-008-01 from ANR-GIS Maladies rares, Paris, France., ANR-07-MRAR-0008,EPP-HMA,Identification des gènes et des mécanismes physio-pathologiques impliqués dans une nouvelle forme de protoporphyrie érythropoïétique et dans des cas rares d'anémie microcytaire hypochrome.(2007), Centre Français des Porphyries Hôpital Louis Mourier, Université Paris Diderot - Paris 7 (UPD7), Génétique fonctionnelle et médicale, Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Infection et inflammation chronique (2I), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Génétique Fonctionnelle de la Souris, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Hopital Louis Mourier - AP-HP [Colombes], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)

Subjects
Liver Cirrhosis, medicine.medical_treatment, Porphyria, Erythropoietic, [SDV]Life Sciences [q-bio], Protoporphyrins, Liver transplantation, Severity of Illness Index, Liver disease, Mice, 0302 clinical medicine, Phospholipids, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, Lipoprotein-X, Mice, Inbred BALB C, Bile acid, [CHIM.ORGA]Chemical Sciences/Organic chemistry, [SDV.BA]Life Sciences [q-bio]/Animal biology, Liver Disease, Hepatobiliary disease, Gastroenterology, Protoporphyrin, 3. Good health, Cholesterol, Phenotype, Heme Biosynthesis, 030211 gastroenterology & hepatology, Erythropoietic protoporphyria, medicine.medical_specialty, Genotype, medicine.drug_class, Kupffer Cells, Cholangitis, Sclerosing, Biology, Bile Acids and Salts, 03 medical and health sciences, Cholestasis, Internal medicine, medicine, Animals, Point Mutation, 030304 developmental biology, Hepatology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, Bile Salt Export Pump, Mice, Inbred C57BL, Disease Models, Animal, Endocrinology, Gene Expression Regulation, Immunology, Hepatocytes, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Ferrochelatase
Abstract

Chantier qualité GA; International audience; BACKGROUND & AIMS: Chronic, progressive hepatobiliary disease is the most severe complication of erythropoietic protoporphyria (EPP) and can require liver transplantation, although the mechanisms that lead to liver failure are unknown. We characterized protoporphyrin-IX (PPIX)-linked hepatobiliary disease in BALB/c and C57BL/6 (Fechm1Pas) mice with mutations in ferrochelatase as models for EPP. METHODS: Fechm1Pas and wild-type (control) mice were studied at 12-14 weeks of age. PPIX was quantified; its distribution in the liver, serum levels of lipoprotein-X, liver histology, contents of bile salt and cholesterol phospholipids, and expression of genes were compared in mice of the BALB/c and C57BL/6 backgrounds. The in vitro binding affinity of PPIX for bile components was determined. RESULTS: Compared with mice of the C57BL/6 background, BALB/c Fechm1Pas mice had a more severe pattern of cholestasis, fibrosis with portoportal bridging, bile acid regurgitation, sclerosing cholangitis, and hepatolithiasis. In C57BL/6 Fechm1Pas mice, PPIX was sequestrated mainly in the cytosol of hepatocytes and Kupffer cells, whereas, in BALB/c Fechm1Pas mice, PPIX was localized within enlarged bile canaliculi. Livers of C57BL/6 Fechm1Pas mice were protected through a combination of lower efflux of PPIX and reduced synthesis and export of bile acid. CONCLUSIONS: PPIX binds to bile components and disrupts the physiologic equilibrium of phospholipids, bile acids, and cholesterol in bile. This process might be involved in pathogenesis of sclerosing cholangitis from EPP; a better understanding might improve diagnosis and development of reagents to treat or prevent liver failure in patients with EPP.

Published
2011

25. Phlebotomies or erythropoietin injections allow mobilization of iron stores in a mouse model mimicking intensive care anemia

Author

Valérie Andrieu, Sarah Millot, Nathalie Pilard, Philippe Montravers, Olivier Thibaudeau, Carole Beaumont, Françoise Muzeau, S. Lasocki, and Philippe Lettéron

Subjects
Male, Resuscitation, Anemia, Iron, Ferroportin, Physiology, Critical Care and Intensive Care Medicine, Mice, Hepcidins, Phlebotomy, Hepcidin, hemic and lymphatic diseases, Intensive care, medicine, Animals, Homeostasis, RNA, Messenger, Cation Transport Proteins, Erythropoietin, biology, business.industry, Interleukin-6, Cell Membrane, medicine.disease, Mice, Inbred C57BL, Disease Models, Animal, Immunology, biology.protein, Microsomes, Liver, business, medicine.drug, Hormone, Antimicrobial Cationic Peptides
Abstract

Anemia in critically ill patients is frequent and consists of chronic disease associated with blood losses. These two mechanisms have opposite effects on iron homeostasis, especially on the expression of the iron regulatory hormone hepcidin. We developed a mouse model mimicking the intensive care anemia to explore iron homeostasis.Experimental study.University-based research laboratory.C57BL/6 mice.Mice received either a single intraperitoneal injection of lipopolysaccharide followed 1 week later by zymosan, or were subjected to repeated phlebotomies by retro-orbital punctures, or both. Several subsets of mice were analyzed over a 14-day period to describe the mouse model of intensive care anemia. Additional mice received erythropoietin injections with or without the zymosan treatment and were killed at day 5, to perform a more detailed analysis.We observed anemia as soon as 5 days after zymosan injection, together with increased messenger RNA (mRNA) levels for interleukin-6 and hepcidin. Phlebotomies alone fully suppressed hepcidin mRNA expression. Interestingly, in mice treated with zymosan and phlebotomies, hepcidin expression was suppressed, despite the persistent increase in interleukin-6. Stimulation of erythropoiesis by erythropoietin injections also led to a decrease in hepcidin mRNA in zymosan-treated mice. In these situations combining inflammation and erythropoiesis stimulation, there was no change in ferroportin, the membrane iron exporter, at the mRNA level, whereas ferroportin protein increased. Macrophage iron stores (assessed by histology using diaminobenzidine staining, or by quantification of nonheme iron and ferritin concentrations) were depleted in the spleen.These results suggest that the erythroid factor dominates over inflammation for hepcidin regulation, and that iron could be mobilized in these situations combining inflammation and erythropoiesis stimulation.

Published
2008

26. Labiomandibular paresthesia caused by endodontic treatment: an anatomic and clinical study

Author

Sarah Millot, P. Bravetti, J.F. Gaudy, Aziz El Haddioui, and Françoise Tilotta-Yasukawa

Subjects
Root canal, Mandibular Nerve, Dentistry, Mandible, Clinical study, Root Canal Filling Materials, Tooth root, Tooth Apex, Root Canal Obturation, medicine, Humans, Exact location, Paresthesia, Zinc Oxide-Eugenol Cement, General Dentistry, Cranial Nerve Injuries, Conventional radiology, Root Canal Irrigants, business.industry, Root Canal Therapy, stomatognathic diseases, medicine.anatomical_structure, Otorhinolaryngology, Surgery, Trigeminal Nerve Injuries, Trigeminal nerve injury, Oral Surgery, Gutta-Percha, business, Cancellous bone, Root Canal Preparation, Extravasation of Diagnostic and Therapeutic Materials
Abstract

Labiomandibular paresthesia after root canal treatment is an accident that is still too frequent despite the development of new endodontic techniques. The aim of this anatomical and clinical study is to advance the understanding of how accidents occur so as to avoid them. This anatomical study made it possible to determine the variability of proximity of the apex of the tooth root to the mandibular bundle, as well as the relationship between the nerve and its satellite artery, and to understand how endodontic filling material spreads into the cancellous bone. The clinical study, which included examination with conventional radiology as well as with imaging techniques, enabled us to identify the exact location of the filling material in relation to the mandibular bundle and to correlate this to the occurrence of clinical symptoms and their diverse manifestations.

Published
2005

27. Erythropoietin Injections Stimulate Spleen BMP4-Dependant Stress Erythropoiesis in a Mouse Model of Generalized Inflammation

Author

Carole Beaumont, Sarah Millot, Philippe Lettéron, Valérie Andrieu, and Sigismond Lasocki

Subjects
medicine.medical_specialty, Kidney, Stromal cell, business.industry, Immunology, Spleen, Inflammation, Cell Biology, Hematology, Biochemistry, medicine.anatomical_structure, Endocrinology, Erythropoietin, Internal medicine, medicine, Erythropoiesis, Bone marrow, medicine.symptom, Progenitor cell, business, medicine.drug
Abstract

Abstract 1983 Poster Board I-1005 Introduction: In mouse, acute anemia leads to the rapid expansion and differentiation of stress erythroid progenitors in the spleen. It has been shown that these progenitors respond to BMP4, Stem Cell Factor and hypoxia and differentiate into stress BFU-E. These are sensitive to high levels of erythropoietin (EPO) and rapidly expand in the spleen, allowing rapid recovery from the anemia (JM Perry et al., Blood 2009, 113:911-918). Inflammation is known to inhibit growth and differentiation of erythroid progenitors and to suppress EPO synthesis in the kidney. However, the effect of pro-inflammatory cytokines on this stress erythropoiesis response is not known. We have recently developed a mouse model of zymosan-induced generalized inflammation and shown that stimulation of erythropoiesis by repeated blood withdrawal or injections of erythropoietin favours iron mobilization from tissue iron stores (S. Lasocki et al., CCM 2008, 36:2388-2394), suggesting that EPO treatment may be beneficial provided effective erythropoiesis can be elicited. Objectives: The aim of our study was to assess the impact of EPO injections on the stress erythropoietic response in this mouse model of chronic inflammation. Methods: Mice (C57BL/6) received a single intraperitoneal injection of zymosan at day 1 (Z1) followed by four consecutive daily injections of EPO at day 5, 6, 7 and 8. Mice were analyzed one day (Z9EPO1), four days (Z12EPO4) or nine days (Z17EPO9) after the final injection and compared to controls, Z alone or EPO alone. Double Ter119/CD71 labelling was used to analyze the different stages of erythroblast differentiation by FACS, in bone marrow and spleen in the different conditions. Spleen BMP4 expression was followed by RT-qPCR and immunohistochemistry. Serum EPO levels were measured by ELISA and haematological parameters were recorded. Results: In the inflammatory condition, bone marrow erythropoiesis is suppressed and does not respond to EPO injections. There is a concomitant increased in the percentage of apoptotic Ter119+ cells. In the spleen, inflammation increases spleen size but only moderately stimulates the percentage of erythroblasts. However, EPO injections lead to a 10-fold increase in the percentage of immature erythroblasts at Z9EPO1, followed three days later (Z12EPO4) by a similar increase in the proportion of mature erythroblasts. This finally results in increased reticulocytes and haemoglobin concentration. In the spleen, BMP4 mRNAs are not stimulated by inflammation but significantly increased by EPO injections, both in normal mice and mice with Zymosan-induced inflammation. The protein BMP4 is expressed by erythroid precursors and stromal cells. Double labelling with F4/80 and BMP4 clearly shows that spleen macrophages are the BMP4-expressing cells following EPO injections in mice with a generalized inflammation. Conclusion: In mouse, bone marrow erythropoiesis is repressed by inflammation as it has been shown for human erythropoiesis and it does not respond to EPO injections. By contrast, spleen stress erythropoiesis is strongly stimulated by injections of EPO despite the presence of inflammation. This results from a strong increase in BMP4 synthesis by spleen macrophages. BMP4 is known to be stimulated by acute anemia but our study is the first report of a direct effect of EPO injections on BMP4 expression in the spleen and of the identification of macrophages as the stromal cells producing BMP4. It will be of interest to find out if bone marrow macrophages in humans can synthesize BMP4 and also contribute to a medullar stress erythropoietic response. Disclosures: No relevant conflicts of interest to declare.

Published
2009

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