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6. Protection against Mycobacterium ulcerans lesion development by exposure to aquatic insect saliva

Author

Marsollier, Laurent, Deniaux, Estelle, Brodin, Priscille, Marot, Agnes, Wondje, Christelle Mbondji, Saint-Andre, Jean-Paul, Chauty, Annick, Johnson, Christian, Tekaia, Fredj, Yeramian, Edouard, Legras, Pierre, Carbonnelle, Bernard, Reysset, Gilles, Eyangoh, Sara, Milon, Genevieve, Cole, Stewart T., and Aubry, Jacques

Subjects
Mycobacterial infections -- Prevention, Skin -- Ulcers, Skin -- Prevention, West Africa -- Health aspects
Abstract

ABSTRACT Background Buruli ulcer is a severe human skin disease caused by Mycobacterium ulcerans. This disease is primarily diagnosed in West Africa with increasing incidence. Antimycobacterial drug therapy is relatively [...]

Published
2007

7. Serial magnetic resonance imaging based assessment of the early effects of an ACE inhibitor on postinfarction left ventricular remodeling in rats

Author

Prunier, Fabrice, Marescaux, Laurent, Franconi, Florence, Thia, Alain, Legras, Pierre, Lejeune, Jean-Jacques, and Furber, Alain

Subjects
ACE inhibitors -- Research -- Health aspects, Heart ventricles -- Research -- Usage -- Health aspects, Biological sciences, Usage, Research, Health aspects
Abstract

Abstract: In vivo assessment of treatment efficacy on postinfarct left ventricular (LV) remodeling is crucial for experimental studies. We examined the technical feasibility of serial magnetic resonance imaging (MRI) for [...]

Published
2005

8. Aquatic plants stimulate the growth of a biofilm formation by Mycobacterium ulcerants in axenic culture and harbor these bacteria in the environment

Author

Marsollier, Laurent, Stinear, Timothy, Aubry, Jacques, Robert, Raymond, Carbonnelle, Bernard, Legras, Pierre, Manceau, Anne-Lise, Bourdon, Sandra, ChristineSaint Andre, Jean Paul, Kouakou, Henri, and Audrain, Christine

Subjects
Mycobacteria -- Growth, Aquatic plants -- Research, Mycobacterium -- Growth, Skin diseases -- Causes of, Company growth, Biological sciences
Abstract

Mycobacterium ulcerans is a pathogen that causes Buruli ulcer a necrotic skin disease prevalent throughout Western Africa and studies indicate that aquatic insects could be transmitting this pathogen. Studies conducted show that crude extracts from the green algae added to BACTEC 7H12B culture medium, reduced to half.

Published
2004

10. Aquatic insects as a vector for Mycobacterium ulcerans

Author

Marsollier, Laurent, Robert, Raymond, Aubry, Jacques, Andre, Jean-Paul Saint, Kouakou, Henri, Legras, Pierre, Manceau, Anne-Lise, Mahaza, Chetaou, and Carbonnelle, Bernard

Subjects
Microbiological research -- Analysis, Microbiology -- Environmental aspects, Mycobacterium -- Physiological aspects, Insects, Aquatic -- Physiological aspects, Infection, Biological sciences
Abstract

Research has been conducted on the role of water insects as Mycobacterium ulcerans host. Results indicate that M. ulcerans can be transmitted to the laboratory mice via the aquatic bug bite.

Published
2002

12. In vivo comparison of the proangiogenic properties of chlordecone and three of its dechlorinated derivatives formed by in situ chemical reduction

Author

Alabed Alibrahim, Eid, primary, Legeay, Samuel, additional, Billat, Pierre-André, additional, Bichon, Emmanuelle, additional, Guiffard, Ingrid, additional, Antignac, Jean-Philippe, additional, Legras, Pierre, additional, Roux, Jérôme, additional, Bristeau, Sébastien, additional, Clere, Nicolas, additional, Faure, Sébastien, additional, and Mouvet, Christophe, additional

Published
2019
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14. Aquatic snails, passive hosts of Mycobacterium ulcerans

Author

Marsollier, Laurent, Severin, Tchibozo, Aubry, Jacques, Andre, Jean-Paul, Saint, Legras, Pierre, Manceau, Anne-Lise, Chauty, Annick, Carbonnelle, Bernard, and Cole, Stewart T.

Subjects
DNA replication -- Research, Aquatic animals -- Genetic aspects, Mycobacteria -- Research, Mycobacterium -- Research, Biological sciences
Abstract

A few aquatic snails that may transitorily harbor Mycobacterium ulcerans without offering favorable conditions for its growth and replication are reported. Results indicate that no mycobacterial growth was detected in aquatic snails and so they may be a passive host of M. ulcerans and other environmental mycobacteria.

Published
2004

15. Voriconazole pharmacokinetics in experimental models of disseminated scedosporiosis: Effect of infection and cyclosporine dosing regimen on voriconazole disposition

Author

Lelièvre, Bénédicte, Abbara, Chadi, Chao de La Barca, Juan Manuel, Godon, Charlotte, Legras, Pierre, Turcant, Alain, Bouchara, Jean-Philippe, Diquet, Bertrand, Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Université d'Angers (UA), 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
[SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

National audience

Published
2015

17. Etude de l'impact sur l'internalisation cellulaire et le comportement sanguin de nanocapsules de siRNA modifiées en surface

Author

Resnier, Pauline, Bejaud, Jérôme, Legras, Pierre, Benvegnu, Thierry, Pecorari, Frédéric, Chourpa, Igor, Benoit, Jean-Pierre, Passirani-Malleret, Catherine, Univ Angers, Okina, Micro et Nanomédecines Biomimétiques (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL), Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Université d'Angers (UA), Institut des Sciences Chimiques de Rennes (ISCR), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Nanomédicaments et Nanosondes, EA 6295 (NMNS), Université de Tours, Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Université de Tours (UT)

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

National audience

Published
2014

18. In vitro and in vivo behaviour of paclitaxel loaded lipid nanocapsules

Author

Groo, Anne-Claire, Bossiere, M., Ailhas, Caroline, Trichard, L., Legras, Pierre, Gravier, Julien, Saulnier, Patrick, Benoit, Jean-Pierre, Lagarce, Frédéric, Micro et Nanomédecines Biomimétiques (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL), Novosibirsk State University, Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Université d'Angers (UA), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), and Univ Angers, Okina

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2014

19. Pharmacokinetic and pharmacodynamic study of Paclitaxel-loaded lipid nanocapsules after intravenous and oral administration in rats, on Paclitaxel resistant tumor

Author

Groo, Anne-Claire, Bossière, M, Trichard, L, Legras, Pierre, Benoit, Jean-Pierre, Lagarce, Frédéric, Micro et Nanomédecines Biomimétiques (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL), Novosibirsk State University, Service Commun Animalerie hospitalo-universitaire (SCAHU), Université d'Angers (UA), and Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP)

Subjects
[SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2014

20. Development of modified siRNA lipid nanocapsules - Evaluation of cellular uptake and stealth properties

Author

Resnier, Pauline, Bejaud, Jérôme, David, Stephanie, Legras, Pierre, Benvegnu, Thierry, Pecorari, Frédéric, Chourpa, Igor, Benoit, Jean-Pierre, Passirani-Malleret, Catherine, Micro et Nanomédecines Biomimétiques (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL), Nanomédicaments et Nanosondes, EA 6295 (NMNS), Université de Tours, Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Université d'Angers (UA), Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Tours (UT), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), and Univ Angers, Okina

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2014

21. Use of triazole antifungal drugs in setting up an animal model of cerebral scedosporiosis

Author

Lelièvre, Bénédicte, Legras, Pierre, Abbara, Chadi, Bouchara, Jean-Philippe, Diquet, Bertrand, Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), and Université d'Angers (UA)

Subjects
Scedosporiosis, [SDV]Life Sciences [q-bio], voriconazole, cerebral diffusion, posaconazole
Abstract

National audience; Scedosporium apiospermum is a soil fungus which may cause severe and often fatal cerebral mycosis in immunocompetent patients in the case of near drowning and in immunosuppressed patients such as lung transplant recipients. Due to the low susceptibility of the fungus to antifungal drugs and to the low permeability of the blood-brain barrier, it might be difficult to reach a therapeutic tissue concentration. Indeed, the diffusion of the drug in the brain depends on several parameters such as integrity of the blood-brain barrier.To evaluate the drug diffusion, two experimental models were developed in immunocompetent and immunosuppressed rats. Inocula of S.apiospermum (strain IHEM 3817): 106 spores in immunocompetent and 105 spores in immunosuppressed rats were administered in the penile vein and a scale (graded from 0 to 9) was established based on weight, clinical and neurological signs evaluated by the tail suspension test. Cerebral involvement was confirmed among others by magnetic resonance imaging of brain, which highlighted differences in localisation of fungal abscesses in brain depending on the immune status. As voriconazole or posaconazole exhibit an in vitro activity against the tested strain (E-test), they were given to the rats at doses ranging from 10 to 50 mg/kg/d by i.v. or oral route, respectively (6 rats per dose and controls). The efficacy criteria was defined as time doubling the survival time and absence of neurological sequelae.Whatever the immune status, the effective doses were 30 mg/kg/d for voriconazole and 50 mg/kg/d for posaconazole. The chosen doses of voriconazole and posaconazole were higher than the doses calculated on the basis of data published for mice, rabbits and guinea pigs.This might be explained by the chosen animal species and criteria of efficacy.So, this infectious model appears to be a valuable tool to evaluate the cerebral diffusion of two antifungal drugs in rats. The data enable to perform pharmacokinetic (PK) and pharmacodynamic (PD) studies for PK-PD modelling.

Published
2013

22. Development of smart siRNA Lipid NanoCapsules

Author

Resnier, Pauline, Bejaud, Jérôme, Gaillard, C, Legras, Pierre, Lautram, Nolwenn, Benvegnu, Thierry, Pecorari, Frédéric, Benoit, Jean-Pierre, Passirani-Malleret, Catherine, Micro et Nanomédecines Biomimétiques (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL), Histoire naturelle de l'Homme préhistorique (HNHP), Muséum national d'Histoire naturelle (MNHN)-Université de Perpignan Via Domitia (UPVD)-Centre National de la Recherche Scientifique (CNRS), Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Université d'Angers (UA), Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS)-Université de Perpignan Via Domitia (UPVD), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)

Subjects
[SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

National audience

Published
2013

23. One-step stealth lipid nanocapsule design for anticancer drug delivery

Author

Lainé, Anne-Laure, Wiber, M, Boussier, M, Legras, Pierre, Vessieres, Anne, Jaouen, Gérard, Benoit, Jean-Pierre, Passirani-Malleret, Catherine, Ingénierie de la Vectorisation Particulaire, Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Micro et Nanomédecines Biomimétiques (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL), Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Université d'Angers (UA), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), and Université Paris sciences et lettres (PSL)

Subjects
[SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

National audience

Published
2012

25. Protective effect of Water bug saliva against M. ulcerans lesion development

Author

Marot, Agnès, Marion, Estelle, D'Alayer, J., Cassisa, Viviane, Robert, René, Eyangoh, Sara, Legras, Pierre, Brodin, Priscille, Marsollier, Laurent, Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Université d'Angers (UA), Analyse et Microséquençage des Protéines (Plate-forme), Institut Pasteur [Paris], Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), Institut Pasteur Korea - Institut Pasteur de Corée, and Institut Pasteur [Paris] (IP)

Subjects
[SDV]Life Sciences [q-bio]
Abstract

International audience; At this day, no specific vaccine against Buruli ulcer is available. BCG vaccination has first been suggested to have incomplete but significant short-term protective effects. Subsequent studies have provided highly controversial results with some showing partial protection against M. ulcerans osteomyelitis. The only study that did not solely rely on BCG scar for assessing BCG vaccination status (a procedure that has been shown to be unreliable when BCG is given under the age of three months which is the case is most African countries), but used vaccine booklet examination, did not find any significant protective effect of routine BCG vaccination against Buruli ulcer. Vaccination based on mycobacterial antigens (Hsp65, Ag85A) showed a short delay in lesion development and borderline impact on bacterial loads. These results demonstrated that the most efficient vaccine for Buruli ulcer does not solely rely on the Mycobacterium alone but is a combination of bacilli- and vector-based molecules as already shown for other microbial agents such as Borrelia and Leishmania. Recently, we have demonstrated that repeated water bug bites free of M. ulcerans could protect against M. ulceransinduced lesions. To test whether vector salivary proteins can protect against M. ulcerans lesion, a mouse model was developed involving intradermal inoculation in the tail of 1000 bacilli together with Water bug salivary gland homogenate to mimic a potential natural transmission. Before M. ulcerans inoculation, mice were immunized by immunogenic salivary proteins purified by affinity chromatography. We showed that salivary proteins confer protection against the M. ulcerans lesion development in mouse model. Moreover, two candidate proteins (isolated form salivary gland homogenate) that are able to bound M. ulcerans surface, were identified and detected in saliva fluid. These proteins were detected in several water bugs families. This work reinforces the concept of using components of arthropod saliva in vaccine strategies against M. ulcerans lesions.

Published
2010

27. High throughput screening for identification of mycolactone targets : Relations between M. ulcerans and nervous system

Author

Marion, Estelle, Marsollier, Laurent, Song, Ok-Ryul, Cassisa, Viviane, Letournel, Franck, Dantec, C., Legras, Pierre, Brodin, Priscille, Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Université d'Angers (UA), Micro et Nanomédecines Translationnelles (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur Korea - Institut Pasteur de Corée, and Réseau International des Instituts Pasteur (RIIP)

Subjects
[SDV]Life Sciences [q-bio]
Abstract

International audience; Buruli ulcer is an infectious disease transmitted by arthropod vectors harboring Mycobacterium ulcerans, a mycobacterium which belong to the same family of bacteria causing tuberculosis and leprosy. The infection causes painless swelling and severe skin lesions. One key feature of M. ulcerans bacterium is its ability to secrete a necrotic toxin, the mycolactone within small lipophilic vesicles, which are critical for the bacterial induced cytotoxicity. The biological knowledge as well as the preventive and therapeutic means for this invalidating disease is still very limited. Our first approach was to investigate whether the mycolactone toxin could be involved in the neutralization of pain by acting directly on the peripheral nervous system without causing destruction of nervous fibers. By use of live time fluorescence microscopy and appropriate markers, we showed that the addition of toxin at sub-toxic dose provokes modification of ionic currents of neuron cells. Based on this ability of the toxin, a molecular high throughput methodology was developed for the screening of a genome wide siRNA library and small molecules inhibitors to enable the search of the cellular targets for the toxin. The cell-based assay relies on automated confocal microscopy on macrophages coupled with dedicated image analysis. These two screening allowed us to identify a putative toxin target, and a toxin inhibitor. A binding assay confirmed that the putative target is a receptor of the toxin. Together these results allowed us to build a potential signaling pathway activated by the mycolactone and implicated in ionic channel activities. The second approach was to confirm this model in the mouse model of M. ulcerans infection and its role in the hypoesthesia of the lesions. Toxin inhibitor, daily administered to mice, which were experimentally infected by M. ulcerans, conducted to the absence of the hypoesthesia of the lesions. Furthermore, a histological study of neuronal fibers did not show a destruction of neuronal cells. Moreover, in vitro studies have showed that M. ulcerans are able to colonize neuronal cells. Then, these results suggested that the hypoesthesia of the M. ulcerans lesions could be caused by a non-destructive process of nervous cells.&nbsp

Published
2010

29. Oral fondaparinux: use of lipid nanocapsules as nanocarriers and in vivo pharmacokinetic study

Author

Ramadan,Alyaa, Lagarce,Frederic, Tessier-Marteau ,Anne, Thomas ,Olivier, Legras,Pierre, Macchi ,Laurent, Saulnier,Patrick, Benoit,Jean Pierre, Ramadan,Alyaa, Lagarce,Frederic, Tessier-Marteau ,Anne, Thomas ,Olivier, Legras,Pierre, Macchi ,Laurent, Saulnier,Patrick, and Benoit,Jean Pierre

Abstract

Alyaa Ramadan1,4, Frederic Lagarce1,3, Anne Tessier-Marteau2, Olivier Thomas1, Pierre Legras5, Laurent Macchi2, Patrick Saulnier1, Jean Pierre Benoit1,31LUNAM Université, Ingénierie de la Vectorisation Particulaire, Inserm U-646, Angers, France; 2Hematology Department, Angers University Hospital, Angers, France; 3Department of Pharmacy, Angers University Hospital, Angers, France; 4Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; 5SCAHU, Animal House, Angers, FranceAbstract: Oral anticoagulant therapy could be advanced using lipid-based nanoparticulate systems. This study examined lipid nanocapsules for their oral absorption potential as the first step in developing oral fondaparinux (Fp) novel carriers. Using phase inversion method and cationic surfactants such as hexadecyltrimethyl ammonium bromide (CTAB) or stearylamine (SA), cationic lipid nanocapsules (cLNCs), loaded with Fp on their surface, were prepared and characterized (zeta potential, size and Fp association efficiency and content). In vivo studies were conducted after single oral increasing doses of Fp-loaded cLNCs (0.5 to 5 mg/kg of Fp) in rats and the concentration of Fp in the plasma was measured by anti-factor Xa activity assay. The monodisperse, (~50 nm), positively charged Fp-cLNCs with high drug loadings demonstrated linear pharmacokinetic profiles of the drug with an increased oral absolute bioavailability (up to ~21%) compatible with therapeutic anticoagulant effect (>0.2 µg/mL).Keywords: oral anticoagulant, fondaparinux, lipid nanocapsules, bioavailability, pharmacokinetics, rats

Published
2011

31. Regulation of Mycolactone, the Mycobacterium ulcerans Toxin, Depends on Nutrient Source

Author

Deshayes, Caroline, primary, Angala, Shiva Kumar, additional, Marion, Estelle, additional, Brandli, Irène, additional, Babonneau, Jérémie, additional, Preisser, Laurent, additional, Eyangoh, Sara, additional, Delneste, Yves, additional, Legras, Pierre, additional, De Chastellier, Chantal, additional, Stinear, Timothy P., additional, Jackson, Mary, additional, and Marsollier, Laurent, additional

Published
2013
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34. Seasonal and Regional Dynamics of M. ulcerans Transmission in Environmental Context: Deciphering the Role of Water Bugs as Hosts and Vectors

Author

Marion, Estelle, primary, Eyangoh, Sara, additional, Yeramian, Edouard, additional, Doannio, Julien, additional, Landier, Jordi, additional, Aubry, Jacques, additional, Fontanet, Arnaud, additional, Rogier, Christophe, additional, Cassisa, Viviane, additional, Cottin, Jane, additional, Marot, Agnès, additional, Eveillard, Matthieu, additional, Kamdem, Yannick, additional, Legras, Pierre, additional, Deshayes, Caroline, additional, Saint-André, Jean-Paul, additional, and Marsollier, Laurent, additional

Published
2010
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35. New starch-based radiotracer for lung perfusion scintigraphy

Author

Lacoeuille, Franck, primary, Hindré, François, additional, Denizot, Benoit, additional, Bouchet, Francis, additional, Legras, Pierre, additional, Couturier, Olivier, additional, Askiénazy, Serge, additional, Benoit, Jean Pierre, additional, and Le Jeune, Jean Jacques, additional

Published
2009
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36. Impact of Mycobacterium ulcerans Biofilm on Transmissibility to Ecological Niches and Buruli Ulcer Pathogenesis

Author

Marsollier, Laurent, primary, Brodin, Priscille, additional, Jackson, Mary, additional, Korduláková, Jana, additional, Tafelmeyer, Petra, additional, Carbonnelle, Etienne, additional, Aubry, Jacques, additional, Milon, Geneviève, additional, Legras, Pierre, additional, André, Jean-Paul Saint, additional, Leroy, Céline, additional, Cottin, Jane, additional, Guillou, Marie Laure Joly, additional, Reysset, Gilles, additional, and Cole, Stewart T, additional

Published
2007
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37. Colonization of the salivary glands of Naucoris cimicoides by Mycobacterium ulcerans requires host plasmatocytes and a macrolide toxin, mycolactone

Author

Marsollier, Laurent, primary, Aubry, Jacques, additional, Coutanceau, Emmanuelle, additional, André, Jean-Paul Saint, additional, Small, Pamela L., additional, Milon, Geneviève, additional, Legras, Pierre, additional, Guadagnini, Stéphanie, additional, Carbonnelle, Bernard, additional, and Cole, Stewart T., additional

Published
2005
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40. Regulation of Mycolactone, the Mycobacterium ulcerans Toxin, Depends on Nutrient Source.

Author

Deshayes, Caroline, Angala, Shiva Kumar, Marion, Estelle, Brandli, Irène, Babonneau, Jérémie, Preisser, Laurent, Eyangoh, Sara, Delneste, Yves, Legras, Pierre, De Chastellier, Chantal, Stinear, Timothy P., Jackson, Mary, and Marsollier, Laurent

Subjects
BURULI ulcer, MYCOBACTERIOSIS, MYCOBACTERIUM tuberculosis, HANSEN'S disease, BACTERIAL toxins, POLYKETIDES
Abstract

Background: Mycobacterium ulcerans, a slow-growing environmental bacterium, is the etiologic agent of Buruli ulcer, a necrotic skin disease. Skin lesions are caused by mycolactone, the main virulence factor of M. ulcerans, with dermonecrotic (destruction of the skin and soft tissues) and immunosuppressive activities. This toxin is secreted in vesicles that enhance its biological activities. Nowadays, it is well established that the main reservoir of the bacilli is localized in the aquatic environment where the bacillus may be able to colonize different niches. Here we report that plant polysaccharides stimulate M. ulcerans growth and are implicated in toxin synthesis regulation. Methodology/Principal Findings: In this study, by selecting various algal components, we have identified plant-specific carbohydrates, particularly glucose polymers, capable of stimulating M. ulcerans growth in vitro. Furthermore, we underscored for the first time culture conditions under which the polyketide toxin mycolactone, the sole virulence factor of M. ulcerans identified to date, is down-regulated. Using a quantitative proteomic approach and analyzing transcript levels by RT-qPCR, we demonstrated that its regulation is not at the transcriptional or translational levels but must involve another type of regulation. M. ulcerans produces membrane vesicles, as other mycobacterial species, in which are the mycolactone is concentrated. By transmission electron microscopy, we observed that the production of vesicles is independent from the toxin production. Concomitant with this observed decrease in mycolactone production, the production of mycobacterial siderophores known as mycobactins was enhanced. Conclusions/Significance: This work is the first step in the identification of the mechanisms involved in mycolactone regulation and paves the way for the discovery of putative new drug targets in the future. [ABSTRACT FROM AUTHOR]

Published
2013
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42. Isolation of Three Mycobacterium ulceransStrains Resistant to Rifampin after Experimental Chemotherapy of Mice

Author

Marsollier, Laurent, Honoré, Nadine, Legras, Pierre, Manceau, Anne Lise, Kouakou, Henri, Carbonnelle, Bernard, and Cole, Stewart T.

Abstract

ABSTRACTBy use of a murine model for Buruli ulcer, Mycobacterium ulceranswas found to be susceptible to rifampin, with the MIC being 0.5 to 1 μg/ml. Three mutants were isolated after rifampin monotherapy. Two were resistant to rifampin at 8 μg/ml, and one was resistant to rifampin at 32 μg/ml. The mutants harbored Ser416Phe mutations and His420Tyr mutations in the rpoBgene, and these mutations have also been found to be responsible for rifampin resistance in the leprosy and tubercle bacilli. The results indicate that while rifampin may be active against M. ulcerans, it should never be used as monotherapy in humans.

Published
2003
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43. Colonization of the salivary glands of Naucoris cimicoides by Mycobacterium ulcerans requires host plasmatocytes and a macrolide toxin, mycolactone

Author

Marsollier, Laurent, Aubry, Jacques, Coutanceau, Emmanuelle, André, Jean-Paul Saint, Small, Pamela L, Milon, Geneviève, Legras, Pierre, Guadagnini, Stéphanie, Carbonnelle, Bernard, and Cole, Stewart T

Abstract

Mycobacterium ulcerans was first identified as the causative agent of Buruli ulcer; this cutaneous tissue-destructive process represents the third most important mycobacterial disease in humans after tuberculosis and leprosy. More recently other life traits were documented. M. ulcerans is mainly detected in humid tropical zones as part of a complex ecosystem comprising algae, aquatic insect predators of the genus Naucoris, and very likely their vegetarian preys. Coelomic plasmatocytes could be the first cells of Naucoris cimicoides to be involved in the infection process, acting as shuttle cells that deliver M. ulcerans to the salivary glands as suggested by both in vitro and in vivo approaches. Furthermore, a key element for the early and long-term establishment of M. ulcerans in Naucoridae is demonstrated by the fact that only mycolactone toxin-producing M. ulcerans isolates are able to invade the salivary glands, a site where they proliferate. Later, the raptorial legs of Naucoris are covered by M. ulcerans-containing material that displays features of biofilms.

45. Aquatic Snails, Passive Hosts of Mycobacterium ulcerans.

Author

Laurent Marsollier, Sévérin, Tchibozo, Aubry, Jacques, Merritt, Richard W., André, Jean-Paul Saint, Legras, Pierre, Manceau, Anne-Lise, Chauty, Annick, Carbonnelle, Bernard, and Cole, Stewart T.

Subjects
*MYCOBACTERIUM, *SKIN diseases, *AQUATIC insects, *ULCERS, *SNAILS, *MYCOBACTERIA, *EPIDEMIOLOGY, *BACTERIOLOGY
Abstract

Accumulative indirect evidence of the epidemiology of Mycobacterium ulcerans infections causing chronic skin ulcers (i.e., Buruli ulcer disease) suggests that the development of this pathogen and its transmission to humans are related predominantly to aquatic environments. We report that snails could transitorily harbor M. ulcerans without offering favorable conditions for its growth and replication. A novel intermediate link in the transmission chain of M. ulcerans becomes likely with predator aquatic insects in addition to phytophage insects. Water bugs, such as Naucoris cimicoides, a potential vector of M. ulcerans, were shown to be infected specifically by this bacterium after feeding on snails experimentally exposed to M. ulcerans. [ABSTRACT FROM AUTHOR]

Published
2004
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