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25 results on '"Pharmacochimie et Biologie pour le Développement (PHARMA-DEV)"'

1. On the risk of further excluding outcast patient populations in South America

Author

Eloy Ruiz, Ramiro Fernández, Francisco Berrospi, Sandro Casavilca-Zambrano, Juan Contreras-Mancilla, Juan Pablo Cerapio, Pascal Pineau, Stéphane Bertani, Instituto Nacional de Enfermedades Neoplasicas [Lima, Pérou] (INEN), Laboratoire Mixte International d'Oncologie Anthropologique Moléculaire = International Joint Laboratory of Molecular Anthropological Oncology (LOAM), Institut de Recherche pour le Développement (IRD [Pérou]), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Organisation Nucléaire et Oncogenèse / Nuclear Organization and Oncogenesis, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), and INCa

Subjects
South america, Hepatology, Peru, Hepatitis B Virus HBV, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, General Medicine, Liver cancer, Amerindian Populations
Abstract

International audience

Published
2023

2. Relationship between dietary fats and serum antioxidants with atheromatic index in regular blood donors

Author

Agathi Pritsa, Maria Parpori, Kyriaki S. Papadopoulou, Ioannis Tsamesidis, Diana Samara, Evgenia Lymperaki, Argyrios Gkinoudis, International Hellenic University, Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), ΓΕΝΙΚΟ ΝΟΣΟΚΟΜΕΙΟ ΝΑΟΥΣΑΣ = Naoussa General Hospital, Aristotle University of Thessaloniki, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD)

Subjects
0301 basic medicine, Index (economics), [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Saturated fat, Blood Donors, 030209 endocrinology & metabolism, Atheromatic index, Antioxidants, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Nutrient, Negatively associated, Humans, Medicine, Food science, Sugar, 2. Zero hunger, chemistry.chemical_classification, 030109 nutrition & dietetics, Nutrition and Dietetics, Regular blood donors, Cholesterol, business.industry, Fatty Acids, Fatty acid, Dietary Fats, 3. Good health, chemistry, Dietary intakes, business, Serum antioxidant status, Polyunsaturated fatty acid
Abstract

International audience; Background & objectives: Nutritional choices, which include dietary fatty acids (FA), vitamins and sugars, have an important significant impact on the development of atheromatic index levels. Controversial opinions exist in the literature regarding the role of different fat types and their association with atheromatic index. We investigated the relationship between dietary intake with different atheromatic index groups of volunteer regular blood donors (rBDs) recognizing them as a healthy population excluding drug and supplements intake and we correlated their values with serum total antioxidant status (sTAS).Material & methods: 150 individuals used in this study were divided in 3 groups according to their atheromatic index (AI = Total cholesterol/HDL) (AI): Group 1 (AI < 3.5) comprised of 50 rBDs, Group 2 (AI 3.5-4.49) of 52 rBDs and Group 3 of 48 rBDs (AI > 4.5). Dietary intake was assessed using the 3 day food recall and the Food Processor, computer program for nutrient analysis. sTAS was measured in all samples and correlated with atheromatic index too.Results: Our study showed that rBDs with low dietary intake of all vitamins, Ω3 fatty acids, trans fatty acids and dietary cholesterol presented an increased atheromatic index. On the other hand rBDs with high dietary intake of saturated fat, total fats, monounsaturated and polyunsaturated fats and sugar showed increased atheromatic index. In addition, groups with the higher atheromatic index presented statistically significant higher total antioxidant status. Trans FA are also positively associated with sTAS and on the other hand dietary cholesterol is negatively associated with sTAS and positively in groups B and C.Conclusions: The results of the present study showed that dietary intake of different types of fatty acids should be used separately as atheromatic index predictors. Moreover, sTAS is correlated with dietary intake of SFA, MUFA, PUFA, Cholesterol, Trans FA and sugar. Finally, the measurement of each fatty acid would be of great value for the screening of lipid metabolism disorders in atheromatic index control.

Published
2020

3. Control of replication of hepatitis B and C virus improves patient and graft survival in kidney transplantation

Author

Marc Hazzan, Sébastien Dharancy, Christophe Legendre, Hélène Fontaine, Alain Duhamel, Nassim Kamar, Benjamin Legendre, Stanislas Pol, Corinne Antoine, Philippe Mathurin, Alexandre Louvet, Laurent Alric, Julien Labreuche, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiopathologie du système immunitaire (Inserm U1223), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Unité de biostatistiques, CRLCC Val d'Aurelle - Paul Lamarque, Physiopathologie des Maladies Inflammatoires de l'Intestin, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Service des Maladies de l'Appareil Digestif et de la Nutrition [CHRU Lille], Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Agence de la biomédecine [Saint-Denis la Plaine], Service Néphrologie et transplantation rénale Adultes [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie et Transplantation rénale [CHRU-lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Néphrologie - Immunologie Clinique [Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-PRES Université de Toulouse, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Unité fonctionnelle d’éthique et médecine légale [AP-HP Hôpital Necker Enfants malades], Hôpital Purpan [Toulouse], and CHU Toulouse [Toulouse]

Subjects
Male, 0301 basic medicine, MESH: Antiviral Agents / therapeutic use, Kidney transplant recipients, [SDV]Life Sciences [q-bio], MESH: Hepatitis B, Chronic / virology, Hepacivirus, Virus Replication, medicine.disease_cause, Gastroenterology, 0302 clinical medicine, Interferon, MESH: Hepatitis C, Chronic / virology, Kidney transplantation, Graft Survival, MESH: Hepatitis B virus / drug effects, virus diseases, Middle Aged, MESH: Kidney Transplantation / mortality, Hepatitis B, Prognosis, MESH: Case-Control Studies, MESH: Hepatitis C, Chronic / drug therapy, 3. Good health, MESH: Hepacivirus / drug effects, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, 030211 gastroenterology & hepatology, medicine.drug, Adult, Hepatitis B virus, medicine.medical_specialty, MESH: Graft Survival, Hepatitis C virus, Antiviral Agents, Virus, 03 medical and health sciences, Hepatitis B, Chronic, MESH: Hepacivirus / physiology, Internal medicine, medicine, Humans, chronic hepatitis C, chronic hepatitis B, Hepatitis, Hepatology, business.industry, MESH: Adult, MESH: Hepatitis B virus / physiology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepatitis C, Chronic, medicine.disease, Kidney Transplantation, 030104 developmental biology, MESH: Virus Replication / drug effects, Viral replication, Case-Control Studies, business, MESH: Female, MESH: Hepatitis B, Chronic / drug therapy
Abstract

International audience; Background & aims: Before antiviral therapy, kidney transplant recipients infected with hepatitis B virus (HBV) or hepatitis C virus (HCV) had poor outcomes. Since the 90s, nucleos(t)ide analogues have been widely used in HBV-infected patients, while interferon-based therapy was rarely used in HCV-infected patients. The aim of this study was to assess the impact of HBV and HCV on patient and graft survival, according to viral replication status.Methods: Data from January 1993 to December 2010 were extracted from the French national database CRISTAL. A total of 31,433 kidney transplant recipients were included, of whom 575, 1,060 and 29,798 had chronic hepatitis B, C, or were not infected, respectively.Results: Ten-year survival was lower in HCV-infected (71.3%) than in HBV-infected (81.2%, p = 0.0004) or non-infected kidney transplant recipients (82.7%, p

Published
2019

4. Herbal medicine for epilepsy seizures in Asia, Africa and Latin America: A systematic review

Author

Mayoura Bounlu, Pierre-Marie Preux, Voa Ratsimbazafy, Farid Boumediene, Geneviève Bourdy, Jaime Luna, François Chassagne, Emilie Auditeau, Jeremy Jost, Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Emory University [Atlanta, GA], Institut de la Francophonie pour la Médecine Tropicale (IFMT), Service de Pharmacie Centrale [CHU Limoges], CHU Limoges, Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, CCSD, Accord Elsevier, Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)

Subjects
Asia, Latin Americans, Chemical models, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Drug Discovery, Text messaging, Humans, Medicine, Medicinal plants, 030304 developmental biology, 2. Zero hunger, Pharmacology, 0303 health sciences, Plants, Medicinal, Traditional medicine, business.industry, Medicinal plant, Chronic epilepsy, medicine.disease, Seizure, 3. Good health, Latin America, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 030220 oncology & carcinogenesis, Ethnopharmacology, Africa, Quality of Life, Plant species, Anticonvulsants, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Pharmacological models, Critical assessment, Medicine, Traditional, Plant Preparations, Herbal medicine, business, Phytotherapy
Abstract

Relevance More than 70 million people suffer epilepsy worldwide. Low availability of anti-epileptic drugs, side-effects and drug-resistant epilepsy affect the quality of life of persons with epilepsy in countries with a poorly developed health system. Herbal medicine is frequently used for this neurological condition. Objectives The main objective was to provide a detailed analysis of Herbal Medicine used for neurological conditions related with epilepsy in Asia, Africa and Latin America. More broadly, this study aims to highlight species with assessed efficacy (cross-cultural use, pharmacological effects on models of epileptic seizures) and safety (toxicological data in laboratory) information, in order to point out species of interest for further studies. A critical assessment of models used in pharmacological evaluations was done. Materials and methods The systematic search for Herbal Medicine treatments for epilepsy was performed considering all the articles published until February 2017 through three scientific databases. It was made with MeSH terms and free text defining the epilepsy seizures and plant species. We included studies carried out in Asia, Africa and Latin America. All articles reporting the use of Herbal Medicine to treat epilepsy seizures and/or their pharmacological evaluation were retained for further analysis. Results The search yielded 1886 articles, from 30 countries. Hundred and six articles published between 1982 and 2017 were included, corresponding to a total of 497 use reports for 351 plant species belonging to 106 families. Three hundred and seventy seven use reports corresponding to 264 species in ethnopharmacological surveys and 120 evaluation reports corresponding to 107 species were noted. Twenty-nine reports, for 29 species, combined both ethnopharmacological and pharmacological evaluation. Fifty eight studies originated from Africa, 35 studies from Asia and 18 from Latin America. Highest use report was noted for rhizomes of Acorus calamus L. (12 use report in 1 country) and leaves of Bacopa monnieri (L.) Wettst. (8 use report in 2 countries). Therefore these species display the highest use convergence. Regarding pharmacological evaluation most studied species were: Leonotis leonurus (L.) R.Br. (4 evaluation reports in 1 country), Uncaria rhynchophylla (Miq.) Miq. ex Havil. (3 evaluation reports in 2 countries) and Calotropis gigantea (L.) Dryand. (3 evaluation reports in 1 country). In vivo models of chronic epilepsy were more relevant than in vitro models or chemical models inducing acute seizures for pharmacological assessment. Conclusion Species with the highest use report were not those with pharmacological evaluation. It will be pertinent to assess the pharmacological effects and safety of medicinal plants used mostly by traditional healers on predictive models of seizures.

Published
2019

5. Antiprotozoal properties of Indonesian medicinal plant extracts

Author

Lucie Paloque, Alexis Valentin, Arba Pramundita Ramadani, Hady Anshory Tamhid, Hugo Belda, Mustofa, Françoise Benoit-Vical, Jumina, Mahardika Agus Wijayanti, Jean-Michel Augereau, Masriani, Laboratoire de chimie de coordination (LCC), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Department of Pharmacology and Therapy, Faculty of Medicine, Universitas Gadjah Mada, Universitas Gadjah Mada, Department of Pharmacy, Faculty of Science & Mathematics, Islamic University of Indonesia, Islamic University of Indonesia, Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT), Department of Chemistry, Faculty of Mathematics and Natural Science, Gadjah Mada University, Department of Parasitology, Faculty of Medicine, Universitas Gadjah Mada, Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), and Université Fédérale Toulouse Midi-Pyrénées

Subjects
0301 basic medicine, Antiparasitic drugs, medicine.drug_class, Plasmodium falciparum, 030106 microbiology, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, 01 natural sciences, 03 medical and health sciences, parasitic diseases, Botany, medicine, Pycnarrhena cauliflora, Babesia divergens, biology, Traditional medicine, Antiparasitic Drugs, Tithonia, biology.organism_classification, 3. Good health, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, Complementary and alternative medicine, Indonesia, Antiprotozoal, Leishmania infantum, Tinospora crispa
Abstract

International audience; Tithonia diversifolia, Cyclea barbata, Tinospora crispa, Arcangelisia flava, Pycnarrhena cauliflora are plants used in Indonesia for the traditional treatment of malaria. In the search for new antiparasitic drugs, the parts traditionally used of these 5 plants were extracted with ethanol and then fractionated with various solvents and evaluated in vitro against Plasmodium falciparum and also against Babesia divergens and Leishmania infantum. Seven crude plant extracts out of 25 tested displayed high antimalarial activities with IC50

Published
2018

6. Quassia 'biopiracy' case and the Nagoya Protocol: A researcher's perspective

Author

Geneviève Bourdy, Eric Deharo, Catherine Aubertin, Valérie Jullian, Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Patrimoines locaux, Environnement et Globalisation (PALOC), Muséum national d'Histoire naturelle (MNHN)-Institut de Recherche pour le Développement (IRD)-Sorbonne Université (SU), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), and Sorbonne Université (SU)-Muséum national d'Histoire naturelle (MNHN)-Institut de Recherche pour le Développement (IRD)

Subjects
INDIANS, 0301 basic medicine, RESOURCES, [SDV]Life Sciences [q-bio], NATURAL BIOACTIVE COMPOUNDS, 030106 microbiology, MULTIDISCIPLINARY APPROACH, Context (language use), AMARA L. SIMAROUBACEAE, Indigenous, FRENCH-GUIANA, Patents as Topic, 03 medical and health sciences, Misconduct, Politics, SEARCH, Drug Discovery, Medicine, Nagoya Protocol, Traditional knowledge, Ratification, SIMALIKALACTONE-D, Pharmacology, Plants, Medicinal, business.industry, Biodiversity, French Guiana, Quassia, 030104 developmental biology, Law, BOLIVIA, ANTIMALARIAL ACTIVITY, business, Allegation
Abstract

International audience; Biopiracy accusations are common in the world of biodiversity research. At the end of 2015, a French NGO accused researchers from the Institut de Recherche pour le Développement (IRD) of biopiracy. These researchers had applied for a patent for a natural bioactive molecule against malaria and cancer, the Simalikalactone E, isolated from Quassia amara L. (Simaroubaceae) leaves. This biopiracy allegation triggered a huge wave of attacks from the media and social networks, and vehement recrimination from political officials in French Guiana against researchers who have been accused of ethical misconduct, by stealing the traditional knowledge of indigenous people. These accusations were made in the contentious context of the ratification of the Nagoya Protocol in the frame of implementing the French law on biodiversity, nature and landscapes. So, in an atmosphere of heightened emotions it is crucial to understand the issues behind these accusations. We describe herein the genesis of our discovery, present the detractors' arguments, and discuss the consequences of such biopiracy denunciations for scientific research. We also address our concerns about the gap between rhetoric and reality and the real impact of the Nagoya Protocol on biodiversity conservation.

Published
2017

7. Time before anti-Toxoplasma IgG seroconversion detection by 7 commercial assays in French pregnant women

Author

Xavier Iriart, Catherine Armengol, Judith Fillaux, Antoine Berry, Pamela Chauvin, Christine Roques-Malecaze, Sophie Cassaing, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)

Subjects
Adult, 0301 basic medicine, Microbiology (medical), Time Factors, [SDV]Life Sciences [q-bio], 030106 microbiology, Antibodies, Protozoan, Toxoplasma gondii, Immunoblot, 03 medical and health sciences, Pregnancy, medicine, Humans, Pregnancy Complications, Infectious, Immunodiagnosis, Seroconversion, Automation, Laboratory, biology, Diagnostic Tests, Routine, business.industry, General Medicine, medicine.disease, biology.organism_classification, Virology, 3. Good health, Infectious Diseases, Immunoglobulin G, Immunology, Female, France, Reagent Kits, Diagnostic, Automated tests, business, Toxoplasma, Toxoplasmosis
Abstract

International audience; We assessed the ability to early detect a toxoplasmic seroconversion between 1 immunoblot (LDBIO II®) and 6 automated assays (TGS TA®, Architect®, Vidas II®, Liaison II®, Platelia®, and Elecsys®), comparing the time before anti-Toxoplasma gondii IgG detection during infection in pregnant women. From 2007 to 2015, 620 sera of 269 women were included. The median durations before positive IgG detection with Vidas II®, Liaison II®, Platelia®, and Elecsys® were significantly longer than Architect® with differential times from 11 to 28days (P

Published
2017

8. Exploring the scope of new arylamino alcohol derivatives: Synthesis, antimalarial evaluation, toxicological studies, and target exploration

Author

Giovanny Garavito, Ben M. Dunn, Silvia Galiano, David W. Wright, Miguel Quiliano, Eric Deharo, Adriana Pabón, Nathan E. Goldfarb, Adela López de Cerain, Ignacio Aldana, Adela Mendoza, Isabelle Fabing, Kim Y. Fong, Ariane Vettorazzi, Silvia Pérez-Silanes, Universidad Pública de Navarra [Espagne] = Public University of Navarra (UPNA), Vanderbilt University [Nashville], Universidad de Antioquia = University of Antioquia [Medellín, Colombia], University of Florida [Gainesville] (UF), Southern California University of Health Sciences, Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique (SPCMIB), Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Universidad Nacional de Colombia [Bogotà] (UNAL), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Southern California University of Health Sciences (SCU), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), and Université de Toulouse (UT)

Subjects
0301 basic medicine, Hemozoin inhibition, Antimalarial, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Parasitemia, Pharmacology, medicine.disease_cause, 01 natural sciences, Antiplasmodial, Mice, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Mannich reaction, Pharmacology (medical), Malaria, Falciparum, biology, Chemistry, Regular Article, Amino Alcohols, Arylamino alcohol, 3. Good health, Treatment Outcome, Infectious Diseases, Biochemistry, Pharmacophore, Drug-Related Side Effects and Adverse Reactions, In silico, Plasmodium falciparum, lcsh:Infectious and parasitic diseases, Plasmepsin II enzyme, Antimalarials, Inhibitory Concentration 50, Structure-Activity Relationship, 03 medical and health sciences, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, In vivo, medicine, Animals, Potency, lcsh:RC109-216, IC50, biology.organism_classification, medicine.disease, Survival Analysis, 0104 chemical sciences, Disease Models, Animal, 010404 medicinal & biomolecular chemistry, 030104 developmental biology, Parasitology, Genotoxicity
Abstract

Synthesis of new 1-aryl-3-substituted propanol derivatives followed by structure-activity relationship, in silico drug-likeness, cytotoxicity, genotoxicity, in silico metabolism, in silico pharmacophore modeling, and in vivo studies led to the identification of compounds 22 and 23 with significant in vitro antiplasmodial activity against drug sensitive (D6 IC50 ≤ 0.19 μM) and multidrug resistant (FCR-3 IC50 ≤ 0.40 μM and C235 IC50 ≤ 0.28 μM) strains of Plasmodium falciparum. Adequate selectivity index and absence of genotoxicity was also observed. Notably, compound 22 displays excellent parasitemia reduction (98 ± 1%), and complete cure with all treated mice surviving through the entire period with no signs of toxicity. One important factor is the agreement between in vitro potency and in vivo studies. Target exploration was performed; this chemotype series exhibits an alternative antimalarial mechanism., Graphical abstract Image 1, Highlights • New aryl-substituted propanol derivatives (APD) show promising antimalarial activity. • γ-amino alcohol moiety is significant antimalarial chemotype. • Compound 22 displays excellent in vivo parasitemia reduction (98%) and complete cure. • APD are active against drug sensitive and multidrug resistant strains.

Published
2016

9. Metabolomic approach of the antiprotozoal activity of medicinal Piper species used in Peruvian Amazon

Author

Wilfredo Ruiz Mesía, Liliana Ruiz-Vásquez, Sandrine Cojean, Bruno Figadère, Pedro Vásquez-Ocmín, Alice Gadea, Anne-Cécile Van Baelen, Sébastien Pomel, Alexandre Maciuk, Lastenia Ruiz Mesía, Guillaume Marti, Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Biomolécules : Conception, Isolement, Synthèse (BioCIS), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-CY Cergy Paris Université (CY), Cibles Thérapeutiques et conception de médicaments (CiTCoM - UMR 8038), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Metatoul - Agromix, MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Laboratoire de Recherche en Sciences Végétales (LRSV), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Laboratorio de Investigación de Productos Naturales Antiparasitarios de la Amazonia (LIPNAA), Centro de Investigaciones de Recursos Naturales de la Amazonía (CIRNA), Universidad Nacional de la Amazonía Peruana [Loreto, Perou] (UNAP)-Universidad Nacional de la Amazonía Peruana [Loreto, Perou] (UNAP), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), MetaToul Agromix, MetaboHUB-MetaToul, and Benson-Rumiz, Alicia

Subjects
Plasmodium, MESH: Mesocricetus, MESH: Antimalarials / isolation & purification, Mice, 0302 clinical medicine, MESH: Ethnopharmacology / methods, Genus, Surveys and Questionnaires, Peru, Drug Discovery, [SDV.BV] Life Sciences [q-bio]/Vegetal Biology, MESH: Animals, Leishmania, 0303 health sciences, biology, Traditional medicine, Amazon rainforest, MESH: Antiprotozoal Agents / metabolism, 030220 oncology & carcinogenesis, Antiprotozoal, Female, MESH: Antimalarials / therapeutic use, antiprotozoal Activity, MESH: Leishmania donovani / drug effects, MESH: Metabolomics / methods, Trypanosoma, medicine.drug_class, Plasmodium falciparum, Antiprotozoal Agents, Leishmania donovani, Metabolomic, Antimalarials, 03 medical and health sciences, MESH: Antiprotozoal Agents / therapeutic use, parasitic diseases, Human Umbilical Vein Endothelial Cells, medicine, Animals, Humans, Metabolomics, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, HUVEC Cells, 030304 developmental biology, Pharmacology, Piper, Mesocricetus, Plant Extracts, MESH: Leishmania donovani / metabolism, 15. Life on land, biology.organism_classification, RAW 264.7 Cells, MESH: Antiprotozoal Agents / isolation & purification, Ethnopharmacology, MESH: Antimalarials / metabolism, MESH: Human Umbilical Vein Endothelial Cells / drug effects, MESH: Human Umbilical Vein Endothelial Cells / metabolism, Medicine, Traditional, Peruvian amazon
Abstract

International audience; Ethnopharmacological relevance : In the Peruvian Amazon as in the tropical countries of South America, the use of medicinal Piper species (cordoncillos) is common practice, particularly against symptoms of infection by protozoal parasites. However, there is few documented information about the practical aspects of their use and few scientific validation. The starting point of this work was a set of interviews of people living in six rural communities from the Peruvian Amazon (Alto Amazonas Province) about their uses of plants from Piper genus: one community of Amerindian native people (Shawi community) and five communities of mestizos. Infections caused by parasitic protozoa take a huge toll on public health in the Amazonian communities, who partly fight it using traditional remedies. Validation of these traditional practices contributes to public health care efficiency and may help to identify new antiprotozoal compounds.Aims of study : To record and validate the use of medicinal Piper species by rural people of Alto Amazonas Province (Peru) and annotate active compounds using a correlation study and a data mining approach.Materials and methods : Rural communities were interviewed about traditional medication against parasite infections with medicinal Piper species. Ethnopharmacological surveys were undertaken in five mestizo villages, namely: Nueva Arica, Shucushuyacu, Parinari, Lagunas and Esperanza, and one Shawi community (Balsapuerto village). All communities belong to the Alto Amazonas Province (Loreto region, Peru). Seventeen Piper species were collected according to their traditional use for the treatment of parasitic diseases, 35 extracts (leaves or leaves and stems) were tested in vitro on P. falciparum (3D7 chloroquine-sensitive strain and W2 chloroquine-resistant strain), Leishmania donovani LV9 strain and Trypanosoma brucei gambiense. Assessments were performed on HUVEC cells and RAW 264.7 macrophages. The annotation of active compounds was realized by metabolomic analysis and molecular networking approach.Results : Nine extracts were active (IC50 ≤ 10 μg/mL) on 3D7 P. falciparum and only one on W2 P. falciparum, six on L. donovani (axenic and intramacrophagic amastigotes) and seven on Trypanosoma brucei gambiense. Only one extract was active on all three parasites (P. lineatum). After metabolomic analyses and annotation of compounds active on Leishmania, P. strigosum and P. pseudoarboreum were considered as potential sources of leishmanicidal compounds.Conclusions : This ethnopharmacological study and the associated in vitro bioassays corroborated the relevance of use of Piper species in the Amazonian traditional medicine, especially in Peru. A series of Piper species with few previously available phytochemical data have good antiprotozoal activity and could be a starting point for subsequent promising work. Metabolomic approach appears to be a smart, quick but still limited methodology to identify compounds with high probability of biological activity.

Published
2021

10. Discovery and preliminary structure–activity relationship studies on tecomaquinone I and tectol as novel farnesyltransferase and plasmodial inhibitors

Author

Joëlle Dubois, David Barker, Alexis Valentin, Melissa M. Cadelis, Brent R. Copp, Marie-Lise Bourguet-Kondracki, University of Auckland [Auckland], Molécules de Communication et Adaptation des Micro-organismes (MCAM), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie des Substances Naturelles (ICSN), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), University of Auckland, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD)

Subjects
Stereochemistry, [SDV]Life Sciences [q-bio], Farnesyltransferase, Plasmodium falciparum, Clinical Biochemistry, Pharmaceutical Science, FTase inhibitor, Tecomaquinone I, Heterocyclic Compounds, 4 or More Rings, 01 natural sciences, Biochemistry, Natural product, Antimalarials, Structure-Activity Relationship, chemistry.chemical_compound, Cell Line, Tumor, Drug Discovery, Animals, Farnesyltranstransferase, Humans, Structure–activity relationship, Enzyme Inhibitors, Molecular Biology, IC50, Pyrans, biology, 010405 organic chemistry, Spectrum Analysis, Organic Chemistry, biology.organism_classification, Anti-plasmodial, 3. Good health, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, chemistry, biology.protein, Molecular Medicine, Dimerization
Abstract

International audience; Biological screening of a library of synthesized benzo[c]chromene-7,10-dione natural products against human farnesyltransferase (FTase) has identified tecomaquinone I (IC50 of 0.065 ± 0.004 μM) as being one of the more potent natural product inhibitors identified to date. Anti-plasmodial screening of the same library against a drug-resistant strain of Plasmodium falciparum identified the structurally-related dichromenol tectol as a moderately active growth inhibitor with an IC50 3.44 ± 0.20 μM. Two novel series of analogues, based on the benzo[c]chromene-7,10-dione scaffold, were subsequently synthesized, with one analogue exhibiting farnesyltransferase inhibitory activity in the low micromolar range. A preliminary structure–activity relationship (SAR) study has identified different structural requirements for anti-malarial activity in comparison to FTase activities for these classes of natural products. Our results identify tecomaquinone I as a novel scaffold from which more potent inhibitors of human and parasitic FTase could be developed.

Published
2016

11. Improved on-chip impedimetric immuno-detection of subpopulations of cells toward single-cell resolution

Author

Karine Reybier, Rémi Courson, Jan Sudor, Armelle Montrose, Anne Marie Gué, Paul-Louis Fabre, Rémi Manczak, Marc Fouet, Équipe Nano Ingénierie et Intégration des Systèmes (LAAS-N2IS), Laboratoire d'analyse et d'architecture des systèmes (LAAS), Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Service Techniques et Équipements Appliqués à la Microélectronique (LAAS-TEAM), Région Midi-Pyrénées (France), University of Toulouse (France), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées, Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)

Subjects
Materials science, immune-detection, Microfluidics, microfluidic, Analytical chemistry, 02 engineering and technology, interdigitated electrode, 01 natural sciences, Redox, Materials Chemistry, Miniaturization, Wafer, cell detection, [SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics, Electrical and Electronic Engineering, Instrumentation, Electrical impedance, business.industry, 010401 analytical chemistry, Metals and Alloys, Impedance, 021001 nanoscience & nanotechnology, Condensed Matter Physics, 0104 chemical sciences, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, Dielectric spectroscopy, Electrode, Optoelectronics, 0210 nano-technology, business, Sensitivity (electronics)
Abstract

International audience; Impedance spectroscopy has gained interest for the quantitative detection of specific cells mainly due to a label-free detection and their miniaturization capability required for integration on chip and development of point-of-care diagnostics. In this paper, we report the study of impedimetric microfluidic devices with improved sensitivity targeting the immuno-detection of cells. The sensitivity of our system was evaluated in terms of the capacity of the electrodes to trap monocytes by immune-reaction with CD14 antibody immobilized on micro-electrode surface. All measurements were performed in faradic mode using a redox probe. The sensitivity was evaluated as a function of the impedance increase recorded at 100 Hz caused by the insulating character of the cell trapped on electrodes. Analyses first confirmed that the sensing performances were significantly improved by using microfluidic. This increase could originate from an increase in the probability of cell trapping and a better organization of cells on the electrode due to the laminar flow. The great sensitivity was recorded with interdigitated electrodes for which the influence of the gap value was evaluated. The maximum sensitivity was reached with the smallest inter-electrodes gap tested (50 µm). This performance was in part attributed to the redox cycling taking place between neighboring fingers that was strongly affected when cells were trapped on the electrodes edges. Furthermore we also demonstrate that the slice of cell concentration for which the sensitivity is maximized is correlated to the area of electrodes. Moreover, the smallest area of interdigitated electrode (0.1 mm length) allowed the detection of as low as 5 cells per mL

Published
2016

12. Electrochemical and Spin-Trapping Properties of para-substituted α-Phenyl-N-tert-butyl Nitrones

Author

Frederick A. Villamena, Pierre Perio, Paul-Louis Fabre, Grégory Durand, Béatrice Tuccio, Marie Rosselin, Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Avignon Université (AU), Institut de Chimie Radicalaire (ICR), Aix Marseille Université (AMU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Ohio State University [Columbus] (OSU), NIH National Heart, Lung, Blood Institute grant RO1HL81248, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)

Subjects
chemistry.chemical_classification, Spin-Trapping, Free Radicals, Spin trapping, 010405 organic chemistry, [SDV]Life Sciences [q-bio], General Chemical Engineering, Kinetics, Nitrones, 010402 general chemistry, Photochemistry, 01 natural sciences, Redox, Antioxidants, 0104 chemical sciences, Nitrone, Oxidative Stress, chemistry.chemical_compound, chemistry, Nucleophile, Electrochemistry, Polar effect, Hydroxymethyl, Cyclic voltammetry
Abstract

International audience; Nitrones are known both as therapeutic antioxidants and efficient spin-traps. In this work, the redox behavior of various para-substituted α-phenyl-N-tert-butyl nitrones (PBN) was studied by cyclic voltammetry. The polar effect of the substituents was found to correlate with the electrochemical properties of the nitronyl function. Compounds bearing an electron-withdrawing group were more easily reduced than those having an electron-donating group and an opposite trend was observed for the oxidation. Ease of oxidation was also computationally rationalized using DFT approach showing increased ease of oxidation with electron donating functionalities. Since electrochemical properties of nitrones are known to correlate with biological properties, this work provides insights in the design of potent nitrone antioxidants. Using cyclic voltammetry the relative rate of superoxide trapping by nitrones was investigated and compared to the classical antioxidant BHT. The determination of the relative rate of phenyl radical trapping was also carried out but showed no clear correlation with the nature of the substituents. This indicates the absence of a polar effect in agreement with previous data and further supports the intermediate nature, that is, non- or weakly nucleophile, of phenyl radical. On the contrary kinetics of hydroxymethyl radical trapping was found to correlate with the nature of the substituents, demonstrating the nucleophilic nature of its addition onto nitrones.

Published
2016

13. Role of ethnopharmacologists in the conservation of endangered animal species

Author

François Chassagne, Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), and Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)

Subjects
0301 basic medicine, Pharmacology, Conservation of Natural Resources, Ecology, [SDV]Life Sciences [q-bio], Endangered Species, conservation, animal species, Endangered species, Species translocation, ethnopharmacologists, Biodiversity, 3. Good health, 03 medical and health sciences, Conservation reliant species, 030104 developmental biology, 0302 clinical medicine, Geography, 030220 oncology & carcinogenesis, Ethnopharmacology, Drug Discovery, Animals
Abstract

International audience; 1. IntroductionThe conservation of biodiversity is an issue of great concern in ethnopharmacology, and has gained a growing interest since the establishment of the Convention on Biological Diversity in 1992. Contributing to the conservation and the sustainable use of biodiversity (i.e. animals and plants species in traditional medicine) has been cited as a research objectives in many ethnopharmacological studies (Etkin, 2001, Heinrich et al., 2009), and it is also clearly highlighted in the scope of the Journal of Ethnopharmacology, which is the scientific journal of reference in the field (Heinrich, 2001). However, in a context of rapid global change, to express concern at the loss of biodiversity is not sufficient, and some authors call for a more proactive role of the ethnopharmacologists (Hedberg, 1993, Heywood, 2011).While the use of endangered plant species has been largely discussed (Moyo and Van Staden, 2014, Stewart, 2003), few ethnopharmacological researches have debated about the use of protected and endangered wildlife. In a recent letter to the editor of Journal of Ethnopharmacology, Nijman and Nekaris (2016) stressed that researchers have an obligation to provide context about the ethical and legal implications of using endangered wildlife in ethnopharmacological surveys. The authors propose to include in the manuscript three important information dealing with the conservation status and legality of trade of animal species reported in the survey. These minimal requirements are particularly useful to address the impact of traditional use on wildlife fauna, and are expected to be employed by many researchers.However, the inclusion of these information should be carefully supplemented by a wide description of the context of these uses, especially the socio-cultural aspect, to avoid misinterpretations of the data. Indeed, ethnopharmacology is a multi-disciplinary field based on approaches from the sociocultural sciences and the natural sciences/medicines (Heinrich and Jäger, 2015), and should not be reduced to a conservationist task. One of the main risk is to lose the confidence of our informants who will no longer share their knowledge with us. As in the case of Traditional Chinese Medicine, Lee and Mills (2000) reported that misinterpretations of the traditional concept by Western conservationists and disrespect of traditional medicine (TM) communities can offend some members of the TM communities and lead to a mistrustful context, which does not serve the achievement of sustainable wildlife use.This comment provides some examples of important contextual data to consider to clearly understand the traditional use of animal species, as well as the role of ethnopharmacologists in the conservation of endangered species by suggesting some areas of intervention.

Published
2017

14. Triterpenoid saponins from Calliandra calothyrsus Meisn. and their antiproliferative activity against two digestive carcinoma human cell lines

Author

Lin Marcellin Messi, Olivier Placide Noté, Joséphine Ngo Mbing, Pierre Lavedan, Marc Vedrenne, Noufou Ouedraogo, Maëlle Carraz, Sandra Bourgeade-Delmas, Dieudonné Emmanuel Pegnyemb, Mohamed Haddad, Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Université de Yaoundé I, Institut de Recherche Agricole pour le Développement [Yaoundé] (IRAD), Institut de Chimie de Toulouse (ICT), and Centre national de la recherche scientifique et technologique [Ouagadougou] (CNRST)

Subjects
[SDV]Life Sciences [q-bio], Cytotoxicity, Phytochemicals, ved/biology.organism_classification_rank.species, Flowers, 01 natural sciences, Triterpenoid saponins, Calliandra calothyrsus, Cell Line, Tumor, Drug Discovery, Carcinoma, medicine, Humans, Cameroon, Oleanolic Acid, Pharmacology, Calothyrsusoside, Molecular Structure, 010405 organic chemistry, ved/biology, Chemistry, Fabaceae, General Medicine, Plant Components, Aerial, Saponins, Carbon-13 NMR, medicine.disease, Antineoplastic Agents, Phytogenic, Triterpenes, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, Biochemistry, Proton NMR, Caco-2 Cells, Drug Screening Assays, Antitumor, Two-dimensional nuclear magnetic resonance spectroscopy, Heteronuclear single quantum coherence spectroscopy
Abstract

International audience; The chemical investigation of the flowers and twigs of Calliandra calothyrsus (Fabaceae) led to the isolation of three new oleanane-type triterpenoid saponins, named calothyrsusosides AC (13). Their structures were established by direct interpretation of their spectral data, mainly HRESIMS, 1D NMR and 2D NMR (1H, 1H NMR DOSY, 13C NMR, COSY, HSQC, HMBC, HSQC-TOCSY and NOESY) and by comparison with literature data. Compounds 1 and 2 were tested for their antiproliferative activity against two digestive carcinoma human cell lines: Hep3B (hepatocellular carcinoma) and Caco-2 (epithelial colorectal adenocarcinoma). Both compounds exhibited an antiproliferative activity against the Hep3B cell line, with IC50 values of 6.0 and 6.5 μM, respectively, while no effect was detected against the epithelial colorectal adenocarcinoma Caco-2 (CC50 > 25 μM).

Published
2020

15. Sacha Inchi Oil (Plukenetia volubilis L.), effect on adherence of Staphylococus aureus to human skin explant and keratinocytes in vitro

Author

Haouaria Belkhelfa, Geneviève Bourdy, Laila Haddioui-Hbabi, Eric Deharo, German Gonzalez-Aspajo, Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, FONdation pour le DEveloppement de la REcherche PHARmaceutique - FONDEREPHAR (FRANCE), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)

Subjects
Keratinocytes, Staphylococcus aureus, Cell Survival, [SDV]Life Sciences [q-bio], Human skin, Context (language use), Plukenetia volubilis L, Skin infection, Biology, medicine.disease_cause, Bacterial Adhesion, Cell Line, Sacha Inchi Oil, Keratinocytes cells, chemistry.chemical_compound, Drug Discovery, Botany, medicine, Humans, Plant Oils, Coco, Trypticase soy agar, Skin, Pharmacology, integumentary system, Traditional medicine, Euphorbiaceae, Human skin explant, 15. Life on land, medicine.disease, biology.organism_classification, medicine.anatomical_structure, chemistry, Dietary Supplements, Keratinocyte, Plukenetia volubilis
Abstract

Ethnopharmacological relevance Plukenetia volubilis L. (Euphorbiaceae) is a domesticated vine distributed from the high-altitude Andean rain forest to the lowlands of the Peruvian Amazon. Oil from the cold-pressed seeds, sold under the commercial name of Sacha Inchi Oil (SIO) is actually much in favour because it contains a high percentage of omega 3 and omega 6, and is hence used as a dietary supplement. SIO is also used traditionally for skin care, in order to maintain skin softness, and for the treatment of wounds, insect bites and skin infections, in a tropical context where the skin is frequently damaged. Aims of the study This study was designed in order to verify whether the traditional use of SIO for skin care would have any impact on Staphylococcus aureus growth and skin adherence, as S. aureus is involved in many skin pathologies ( impetigo, folliculitis, furuncles and subcutaneous abscesses) being one if the main pathogens that can be found on the skin. Therefore, our objective was to assess SIO bactericidal activity and interference with adherence to human skin explants and the keratinocyte cell line. Cytotoxicity on that cells was also determined. The activity of SIO was compared to coconut oil (CocO), which is widely used for skin care but has different unsaturated fatty acids contents. Materials and methods Laboratory testing with certified oil, determined antibacterial activity against radio labelled S. aureus . Cytotoxic effects were measured with XTT on keratinocyte cells and with neutral red on human skin explants; phenol was used as cytotoxic control. Adherence assays were carried out by mixing H3-labelled S. aureus bacteria with keratinocyte cells and human skin explants, incubated with oils 2 h before (to determine the inhibition of adherence, assimilated to a preventive effect) or 2 h after the contact of the biological material with S. aureus (to assess the detachment of the bacteria, assimilated to a curative effect). Residual radioactivity measured after washings made it possible to determine the adherence intensity. Bactericidal effect was determined by colony counting on trypticase soy agar. Results Laboratory assays showed that SIO and CocO, tested undiluted, were not cytotoxic on keratinocytes nor human explants and were not bactericidal neither. SIO was more active as antiadherent (preventive) than CocO on keratinocytes. There was no significant difference between detachment effects (curative) of both oils on keratinocytes but SIO was almost 5 times more active on the detachment of S. aureus from human skin explants. Conclusion From that study it can be concluded that the use of SIO on dermal cells is safe and efficient in the inhibition of S. aureus adherence. Our results tend to support the traditional use of undiluted SIO in skin care.

Published
2015

16. Risk Factors of Pneumocystis Pneumonia in Solid Organ Recipients in the Era of the Common Use of Posttransplantation Prophylaxis

Author

Laurence Lavayssière, O. Roques, Jean-François Magnaval, Sandie Menard, Lionel Rostaing, A. Del Bello, Sophie Cassaing, Olivier Cointault, Antoine Berry, Judith Fillaux, Rose-Anne Lavergne, Isabelle Cardeau-Desangles, Pamela Chauvin, Nassim Kamar, Xavier Iriart, L. Esposito, T. Challan Belval, CHU Toulouse [Toulouse], Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Graft Rejection, Male, Antifungal Agents, [SDV]Life Sciences [q-bio], Cytomegalovirus, Pneumocystis carinii, Pneumocystis pneumonia, Clinical research, Postoperative Complications, Risk Factors, Immunology and Allergy, Pharmacology (medical), Univariate analysis, risk stratification, Pneumonia, Pneumocystis, Graft Survival, risk assessment, Middle Aged, complication: infectious, practice, Tissue Donors, 3. Good health, fungal, Cytomegalovirus Infections, Female, Risk assessment, infection and infectious agents, medicine.medical_specialty, infectious disease, lung, disease: infectious, Immunocompromised Host, Internal medicine, Trimethoprim, Sulfamethoxazole Drug Combination, medicine, Humans, Retrospective Studies, Transplantation, business.industry, Organ Transplantation, Odds ratio, Antibiotic Prophylaxis, medicine.disease, Transplant Recipients, Tacrolimus, Confidence interval, Surgery, Case-Control Studies, business, Follow-Up Studies
Abstract

International audience; Pneumocystis pneumonia (PCP) in solid organ transplant (SOT) recipients becomes rare in the immediate posttransplantation period thanks to generalized prophylaxis. We aimed to identify the predictive factors for PCP in the era of universal prophylaxis and to propose a strategy for preventing PCP beyond the first year after transplantation. In a retrospective case-control study, 33 SOT cases with PCP diagnosed between 2004 and 2010 were matched with two controls each to identify risk factors for PCP by uni- and multivariate analysis. All the patients benefited from 6 months of posttransplantation trimethoprim-sulfamethoxazole prophylaxis. Most PCP in SOT patients occurred during the second year posttransplantation (33%). By univariate analysis, age, nonuse of tacrolimus, total and CD4 lymphocyte counts, gamma-globulin concentration and cytomegalovirus (CMV) infection appeared to be PCP risk factors. In the final multivariate analysis, age (adjusted odds ratio [OR] 3.7, 95% confidence interval [CI]: 1.3-10.4), CMV infection (OR: 5.2, 95% CI: 1.8-14.7) and total lymphocyte count (OR: 3.9, 95% CI: 1.4-10.7) were found to be independently associated with PCP. The second year posttransplantation appeared to be the new period of highest risk of PCP. Age, CMV viremia and lymphocytes were the most pertinent predictive criteria to evaluate the risk of PCP in clinical practice.

Published
2015

17. Cloning and characterization of a basic cysteine-like protease (cathepsin L1) expressed in the gut of larval Diaprepes abbreviatus L. (Coleoptera: Curculionidae)

Author

Dov Borovsky, Pierre Rougé, John E. Ramos, Sulley K. Ben-Mahmoud, Robert G. Shatters, Charles A. Powell, Guy Smagghe, University ofFlorida, USDA-ARS : Agricultural Research Service, Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Universiteit Gent = Ghent University [Belgium] (UGENT), University of Florida [Gainesville] (UF), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), and Universiteit Gent = Ghent University (UGENT)

Subjects
Models, Molecular, Bacterial expression, Physiology, Cathepsin L, [SDV]Life Sciences [q-bio], Molecular Sequence Data, Cathepsin E, Cathepsin F, Cathepsin B, 3D modeling, Basic cathepsin L1, Cathepsin O, Cathepsin H, Cathepsin L1, Animals, Amino Acid Sequence, Cloning, Molecular, Cathepsin, biology, Diaprepes abbreviatus, Hydrogen-Ion Concentration, Enzyme characterization, Molecular biology, Recombinant Proteins, Gastrointestinal Tract, Biochemistry, Larva, Insect Science, biology.protein, Weevils
Abstract

International audience; Diaprepes abbreviatus is an important pest that causes extensive damage to citrus in the USA. Analysis of an expressed sequence tag (EST) library from the digestive tract of larvae and adult D. abbreviatus identified cathepsins as major putative digestive enzymes. One class, sharing amino acid sequence identity with cathepsin L's, was the most abundant in the EST dataset representing 14.4% and 3.6% of the total sequences in feeding larvae and adults, respectively. The predominant cathepsin (Da-CTSL1) among this class was further studied. Three dimensional modeling of the protein sequence showed that the mature Da-CTSL1 protein folds into an expected cathepsin L structure producing a substrate binding pocket with appropriate positioning of conserved amino acid residues. A full-length cDNA was obtained and the proCTSL1 encoding sequence was expressed in Rosetta™ Escherichia coli cells engineered to express tRNAs specific for eukaryotic codon usage. The Da-CTSL1 was expressed as a fusion protein with GST and His6 tags and purified in the presence of 1% Triton X-100 by Ni-NTA affinity and size exclusion chromatography. Recombinant mature Da-CTSL1 (23 KDa) exhibits optimal activity at pH 8, rather than at acidic pH that was shown of all previously characterized cathepsins L. Substrate specificity supports the hypothesis that Da-CTSL1 is a unique basic cathepsin L and protease inhibitor studies also suggest unique activity, unlike other characterized acidic cathepsin Ls. This paper describes for the first time a prokaryotic expression system for the production of a functional eukaryotic cathepsin L1 from larval gut of D. abbreviatus.

Published
2015

18. In silico tools for exploring potential human allergy to proteins

Author

Maria Hayes, Annick Barre, Corinne Herouet-Guicheney, Erwin Ludo Roggen, Pierre Rougé, Teagasc - The Agriculture and Food Development Authority (Teagasc), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Bayer SAS, 3Rs Management and Consulting ApS, EU COST Action ImpARAS FA1402, Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)

Subjects
Allergy, [SDV]Life Sciences [q-bio], In silico, Computational biology, Biology, Bioinformatics, medicine.disease_cause, 01 natural sciences, 03 medical and health sciences, Allergen, immune system diseases, Drug Discovery, otorhinolaryngologic diseases, medicine, Food allergens, 030304 developmental biology, 0303 health sciences, Novel protein, 010401 analytical chemistry, respiratory system, medicine.disease, proteins, respiratory tract diseases, 0104 chemical sciences, human allergy, Molecular Medicine
Abstract

International audience; Bioinformatics can help scientists to develop hypotheses about proteins that may need to be tested further for risks of causing allergy. In silico methodologies and tools like databases and comparison software, play an important role in the assessment of protein allergenicity and allergenicity mechanisms. They can identify whether a novel protein is an existing allergen and/or has the potential to cross-react with an existing allergen. They cannot identify whether a novel protein will ‘become’ an allergen. AllergenOnline is the tool currently used for the safety assessment of novel proteins, but other tools are also available including the Structural Database of Allergenic Proteins (SDAP) and AllerTOP. Information concerning PeptideRanker, as well as the Hydrophobic Cluster Analysis (HCA) method used for identifying IgE-binding epitopes in food allergens is discussed.

Published
2015

19. Detection, identification and quantification by 1H NMR of adulterants in 150 herbal dietary supplements marketed for improving sexual performance

Author

Robert Martino, Véronique Gilard, Stéphane Balayssac, Myriam Malet-Martino, Aurélie Tinaugus, Nathalie Martins, Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique (SPCMIB), Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), and Université de Toulouse (UT)

Subjects
Magnetic Resonance Spectroscopy, Sexual Behavior, Clinical Biochemistry, Pharmaceutical Science, Analytical Chemistry, chemistry.chemical_compound, Labelling, Drug Discovery, medicine, [CHIM]Chemical Sciences, ComputingMilieux_MISCELLANEOUS, Spectroscopy, Marketing, Chromatography, Traditional medicine, Chemistry, Aphrodisiacs, Phosphodiesterase 5 Inhibitors, Tadalafil, 3. Good health, Vardenafil, Batch Number, Dietary Supplements, Proton NMR, Flibanserin, Plant Preparations, Drug Contamination, Icariin, Hydrogen, medicine.drug
Abstract

One hundred and fifty dietary supplements (DS) marketed to increase sexual performance were analyzed. All these formulations were claimed to contain only natural compounds, plant extracts and/or vitamins. (1)H NMR spectroscopy was used for detecting the presence of adulterants and for their identification and quantification. Mass spectrometry was used as a complementary method for confirming the chemical structures. 61% of DS were adulterated with phosphodiesterase-5 inhibitors (PDE-5i) (27% with the PDE-5i medicines sildenafil, tadalafil and vardenafil, and 34% with their structurally modified analogues). Among them, 64% contained only one PDE-5i and 36% mixtures of two, three and even four. The amounts of PDE-5i medicines were higher than the maximum recommended dose in 25% of DS tainted with these drugs. Additional 5.5% DS included other drugs for the treatment of sexual dysfunction (yohimbine, flibanserin, phentolamine, dehydroepiandrosterone or testosterone). Some DS (2.5%) contained products (osthole, icariin) extracted from plants known to improve sexual performance. Only 31% of the samples could be considered as true herbal/natural products. A follow-up over time of several DS revealed that manufacturers make changes in the chemical composition of the formulations. Lack of quality or consistent manufacture (contamination possibly due to inadequate cleaning of the manufacturing chain, presence of impurities or degradation products, various compositions of a given DS with the same batch number, inadequate labelling) indicated poor manufacturing practices. In conclusion, this paper demonstrates the power of (1)H NMR spectroscopy as a first-line method for the detection of adulterated herbal/natural DS and the need for more effective quality control of purported herbal DS.

Published
2015

20. Performance of anti-HEV assays for diagnosing acute hepatitis E in immunocompromised patients

Author

Nassim Kamar, Jean-Marie Péron, Lionel Rostaing, Jacques Izopet, Sabine Chapuy-Regaud, Marcel Miedougé, Sébastien Lhomme, Laurent Alric, Florence Abravanel, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Hôpital de Rangueil, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)

Subjects
interquartile range, [SDV]Life Sciences [q-bio], viruses, medicine.medical_treatment, First line, hepatitis E virus, medicine.disease_cause, Sensitivity and Specificity, Serology, open reading frames, Immunoenzyme Techniques, Immunocompromised Host, 03 medical and health sciences, Sensitivity, 0302 clinical medicine, Hepatitis E virus, Interquartile range, Virology, medicine, international unit, Humans, Serologic Tests, Hepatitis Antibodies, 030212 general & internal medicine, Anti hev, 0303 health sciences, 030306 microbiology, Acute hepatitis E, business.industry, IQR, virus diseases, Immunosuppression, Hepatitis E, medicine.disease, digestive system diseases, 3. Good health, IU, Infectious Diseases, Immunoglobulin M, HEV, Immunoglobulin G, Immunology, Specificity, business, ORF
Abstract

International audience; Hepatitis E virus is an emerging concern in immunocompromised patients, who may become chronically infected. This prompted us to assess the performance of two anti-HEV IgG and IgM assays for diagnosing acute HEV infections. The specificities of the assays were estimated by testing samples from 2 to 3 year-old French children and blood donors and their sensitivities by testing 40 immunocompromised patients acutely infected. Both anti-HEV IgM assays were highly specific (99.6% and 100%). The sensitivity of the Adaltis was 87.5%, and that of Wantai was 85%. The specificities of anti-HEV IgG Wantai (97.8%) and Adaltis tests (89.5%, p=0.1) were similar but the Wantai test was more sensitive (45%) than the Adaltis test (15%, p

Published
2013

21. Electrochemical behavior of indolone-N-oxides: Relationship to structure and antiplasmodial activity

Author

Pierre Perio, Karine Reybier, Paul-Louis Fabre, Hany Ibrahim, Françoise Nepveu, Armelle Montrose, Thi Hoang Yen Nguyen, Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Laboratoire de génie chimique [ancien site de Basso-Cambo] (LGC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, Centre National de la Recherche Scientifique - CNRS (FRANCE), Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE), Institut de Recherche pour le Développement - IRD (FRANCE), Université Toulouse III - Paul Sabatier - UT3 (FRANCE), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Laboratoire de Génie Chimique (LGC), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Institut National Polytechnique de Toulouse - INPT (FRANCE)

Subjects
Indolone-N-oxides, Nitroxide mediated radical polymerization, Indoles, Cyclic voltammetry, Stereochemistry, Plasmodium falciparum, Antiprotozoal Agents, Biophysics, Protonation, 010402 general chemistry, 01 natural sciences, Redox, Nitrone, law.invention, Structure-Activity Relationship, Antimalarials, 03 medical and health sciences, chemistry.chemical_compound, Electron transfer, [CHIM.GENI]Chemical Sciences/Chemical engineering, law, Electrochemistry, Radical, Génie chimique, Phenyl group, Physical and Theoretical Chemistry, Electron paramagnetic resonance, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Radical nitroxide anion, Electron Spin Resonance Spectroscopy, Oxides, General Medicine, 0104 chemical sciences, 3. Good health, chemistry, nitroxide anion, EPR, Hydrophobic and Hydrophilic Interactions, Oxidation-Reduction
Abstract

International audience; Indolone-N-oxides exert high parasiticidal activity at the nanomolar level in vitro against Plasmodiumfalciparum, the parasite responsible for malaria. The bioreductive character of these molecules was investigated using cyclic voltammetry and EPR spectroelectrochemistry to examine the relationship between electrochemical behavior and antimalarial activity and to understand theirmechanisms of action. For all the compounds (37 compounds) studied, the voltammograms recorded in acetonitrile showed a well-defined and reversible redox couple followed by a second complicated electron transfer. The first reduction (−0.88 VbE1/2b−0.50 V vs. SCE) was attributed to the reduction of the N-oxide function to form a radical nitroxide anion. The second reduction (−1.65 VbE1/2b−1.14 V vs. SCE) was assigned to the reduction of the ketone function. By coupling electrochemistry with EPR spectroscopy, the EPR spectra confirmed the formation of the nitroxide anion radical.Moreover, the experiments demonstrated that a slowprotonation occurs at the carbon of the nitrone function and not at the NO function. A relationship between electrochemical behavior and indolone-N-oxide structure can be established for compounds with R1=―OCH3, R2=H, and electron-withdrawing substituents on the phenyl group at R3. The results help in the design of new molecules with more potent in vivo antimalarial activity.

Published
2012

22. Aqueous extract of Vitex trifolia L. (Labiatae) inhibits LPS-dependent regulation of inflammatory mediators in RAW 264.7 macrophages through inhibition of Nuclear Factor kappa B translocation and expression

Author

Dominique Laurent, Serge Pauillac, Mariko Matsui, Bernard Pipy, Shilpa Kumar-Roiné, Agnès Coste, Minou Adib-Conquy, Institut Pasteur de Nouvelle-Calédonie, Réseau International des Instituts Pasteur (RIIP), Cytokines et Inflammation, Institut Pasteur [Paris], Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD), Polarisation des Macrophages et Récepteurs Nucléaires dans les Pathologies Inflammatoires et Infectieuses, IFR50-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Bactéries anaérobies et Toxines, Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR50, Institut Pasteur [Paris] (IP), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), and Université de Toulouse (UT)-Université de Toulouse (UT)-IFR50

Subjects
Lipopolysaccharides, Chemokine, Lipopolysaccharide, Anti-Inflammatory Agents, Gene Expression, Vitex, Nuclear factor kappa B, Mice, chemistry.chemical_compound, 0302 clinical medicine, Vitex trifolia, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Drug Discovery, Gene expression, Chemokine CCL3, 2. Zero hunger, 0303 health sciences, biology, Traditional medicine, Chemistry, NF-kappa B, Real-time polymerase chain reaction, 030220 oncology & carcinogenesis, Cytokines, Inflammation Mediators, Chemokines, Anti-inflammatory activity, 03 medical and health sciences, In vivo, Animals, RNA, Messenger, 030304 developmental biology, Inflammation, Pharmacology, Cyclooxygenase 2 Inhibitors, Plant Extracts, Macrophages, Transcription Factor RelA, NF-kappa B p50 Subunit, Biological Transport, COX-2, biology.organism_classification, Molecular biology, Chemokine CXCL10, Cyclooxygenase 2, Apoptosis, biology.protein, Phytotherapy
Abstract

Ethnopharmacological relevance: Vitex trifolia L. (Labiatae), a widespread tree found from the Asia-Pacific to the east Africa regions is used in the traditional medicine of the Pacific islands to treat inflammatory-associated conditions. Aim of the study: We herein evaluated its in vitro regulatory effects on the expression profile of lipopolysaccharide (LPS)-induced inflammatory genes focusing on regulation of chemokines C-X-C motif 10 (CXCL-10) and C-C motif ligand 3 (CCL-3) and cyclo-oxygenase (COX)-2. Furthermore, the plant effect on the LPS-mediated activation of Nuclear Factor kappa B (NF-kappa B) was also studied. Materials and methods: Aqueous extract of Vitex trifolia leaves was prepared and evaluated for its effect on LPS-induced stress and toxicity-related genes in RAW 264.7 macrophage cells using RT2 Profiler Polymerase Chain Reaction (PCR) Array System. Effects of the extract on LPS-induced chemokines CCL-3 and CXCL-10, COX-2, and NF-kappa B p50 and p65 mRNA levels were also studied using Reverse Transcription quantitative PCR (RT-qPCR) technique. Translocation of the nuclear factor was further assessed by measuring its nuclear p65 subunit via an ELISA-based TransAM method. Results: Vitex trifolia extract at 5000 mu g/ml exerted a significant inhibitory effect on the expression of various LPS-induced inflammatory genes in RAW 264.7 cells after 8 h of incubation time. Using RT-qPCR, this anti-inflammatory effect was further confirmed by significant inhibition of CCL-3 and CXCL-10 mRNA production in LPS-stimulated RAW 264.7 cells upon treatment with 2500 mu g/ml of Vitex trifolia extract. Furthermore, the inhibitory activity of this plant on LPS-induced COX-2 mRNA was also observed at a concentration of 2500 mu g/ml in a time-dependent manner. TransAM assays showed that LPS-induced NF-kappa B translocation was also inhibited by Vitex trifolia extract even at a concentration of extract as low as 250 mu g/ml. RT-qPCR assays showed that aqueous extract of Vitex trifolia leaves had a significant inhibitory activity on LPS-induced p50 mRNA synthesis. Interestingly, however, no effect on p65 subunit mRNA expression was observed. Moreover, PCR array analysis showed that LPS-induced inflammatory and apoptosis genes under NF-kappa B control are also repressed by the extract. Conclusion: The anti-inflammatory properties of Vitex trifolia extract seem associated with inhibition of NF-kappa B translocation through a reduction in the expression level of NF-kappa B p50 but interestingly not p65 subunit mRNA. The regulatory effects of Vitex trifolia on NF-kappa and consequently on inflammation mediators such as chemokines CCL-3 and CXCL-10, and COX-2 provide new evidence of its efficacy and emphasise its high potential therapeutic value. However, further in vivo experiments are still required to validate its utilization as a remedy against inflammatory diseases.

Published
2012

23. Contribution of molecular diagnosis to the management of cutaneous leishmaniasis in travellers

Author

Sandie Menard, Jean-François Magnaval, Sophie Cassaing, Guillaume Martin-Blondel, Alexis Valentin, Judith Fillaux, Rose-Anne Lavergne, Pamela Chauvin, S. Arnaud, Christine Roques-Malecaze, Xavier Iriart, Antoine Berry, Bruno Marchou, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Parasitologie et Mycologie, CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Service des maladies infectieuses et tropicales [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Laboratoire d'Anthropobiologie (LA), École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Service de Parasitologie et Mycologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service Maladies infectieuses et tropicales [CHU Toulouse], Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Pagès, Nathalie, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Male, Microbiology (medical), Adolescent, diagnosis, [SDV]Life Sciences [q-bio], 030231 tropical medicine, Direct examination, Leishmaniasis, Cutaneous, Polymerase Chain Reaction, Sensitivity and Specificity, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Cutaneous leishmaniasis, medicine, Humans, Child, leishmaniasis, Aged, Aged, 80 and over, Leishmania, Travel, 0303 health sciences, biology, cutaneous, 030306 microbiology, business.industry, Leishmaniasis, Sequence Analysis, DNA, sequencing, General Medicine, Middle Aged, medicine.disease, biology.organism_classification, Optimal management, 3. Good health, [SDV] Life Sciences [q-bio], PCR, Infectious Diseases, Molecular Diagnostic Techniques, Child, Preschool, Immunology, Female, Identification (biology), business
Abstract

International audience; Cutaneous leishmaniasis is one of the most frequent skin diseases occurring after travelling in endemic areas. Optimal management requires identification of the species of Leishmania involved. In this study we aimed to evaluate the use of molecular diagnosis as routine, in comparison with direct examination and culture. Thirty positive diagnoses were carried out between 2007 and 2013. Classical PCR enabled 11 positive cases to be identified that were found to be negative by conventional methods. Sequencing led to the identification of eight different species. Routine use of PCR and sequencing appears very efficient in the management of cutaneous leishmaniasis.

Published
2014

24. Electrical stimulation superimposed onto voluntary muscular contraction reduces deterioration of both postural control and quadriceps femoris muscle strength

Author

Eric Margnes, Vincent Chaubet, Thierry Paillard, Yrieix Francois, Gerard Gonzalez, Liliane Borel, J.-L. Jully, Julien Maitre, Mouvement, Équilibre, Performance, Santé (MEPS), Université de Pau et des Pays de l'Adour (UPPA), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)

Subjects
Male, Volition, Muscle Strength Dynamometer, medicine.medical_specialty, Contraction (grammar), Posture, Stimulation, Physical strength, Quadriceps Muscle, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Pressure, medicine, Humans, Force platform, Muscle Strength, ComputingMilieux_MISCELLANEOUS, Analysis of Variance, Muscle fatigue, business.industry, General Neuroscience, 030229 sport sciences, Electric Stimulation, Quadriceps femoris muscle, Muscle Fatigue, Physical therapy, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, business, 030217 neurology & neurosurgery, Muscle Contraction, Muscle contraction
Abstract

Fatiguing exercise of the quadriceps femoris muscle degrades postural control in human subjects. The aim of this work was to compare the effects of the fatigue of the quadriceps femoris induced by voluntary muscular contraction (VC), and by electrical stimulation (ES) superimposed onto voluntary muscular contraction (VC+ES), on postural control and muscle strength. Fourteen healthy young adults participated in the study. Postural control and muscle strength were evaluated using a stable force platform and an isokinetic dynamometer, respectively, before (PRE condition) and after the completion of each fatiguing exercise (immediately: POST condition; after a 5 min recovery time: POST 5 condition). In POST, both postural control and muscle strength were impaired by both fatiguing exercises. However, the impairment was higher for VC than for VC+ES. In POST 5, for both fatiguing exercises, postural control recovered its initial level while muscle strength did not. These results suggest that superimposing ES onto voluntary muscular contractions (VCs) impaired muscle strength and postural control less than did VCs alone. However the duration of recovery of these two neurophysiological functions did not differ for the two fatiguing exercises. For both exercises, postural control was restored faster than the ability to produce muscular strength.

Published
2010

25. Prospective evaluation of the aetiological profile of acute pancreatitis in young adult patients

Author

Louis Buscail, Jean-Marie Peron, Adrian Culetto, Barbara Bournet, Laurent Alric, Audrey Haennig, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), CHU Toulouse [Toulouse], Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)

Subjects
Adult, Male, Endoscopic ultrasound, Pediatrics, medicine.medical_specialty, Adolescent, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Magnetic-resonance cholangiopancreatography, Prospective evaluation, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Hereditary pancreatitis, medicine, Humans, Medical history, Prospective Studies, Young adult, Aged, Genetic testing, Aged, 80 and over, Magnetic resonance cholangiopancreatography, medicine.diagnostic_test, Hepatology, business.industry, Age Factors, Gastroenterology, Middle Aged, medicine.disease, Acute pancreatitis, Surgery, 3. Good health, Pancreatitis, 030220 oncology & carcinogenesis, Acute Disease, Etiology, Female, 030211 gastroenterology & hepatology, business, Cannabis consumption, Follow-Up Studies
Abstract

International audience; Background: The aetiologies of acute pancreatitis in young adult patients are poorly known.Aims: To prospectively evaluate the causes of acute pancreatitis in patients aged less than 35 years.Methods: Overall, 309 consecutive patients admitted to our centre for acute pancreatitis received first-line investigations, including medical history, standard laboratory tests, abdominal ultrasound and computed tomography. If no aetiology was found, second-line investigations were performed, including endoscopic ultrasound, magnetic-resonance cholangiopancreatography and genetic testing in cases of idiopathic pancreatitis.Results: Overall, 66 patients aged between 16 and 35 years were included. After first-line investigations, 49% of cases of acute pancreatitis remained idiopathic. Second-line investigations reduced this rate to 21%. The frequency of aetiologies for acute pancreatitis significantly differed in adults aged ≤ 35 compared to those aged >35 years: biliary aetiology was less frequent (23% versus 43%, p=0.003) as well as alcohol-related (8% versus 24%, p=0.01); drug-induced was more common (16% versus 4%, p=0.0007), as well as cannabis-related (13% versus 1%, p

Published
2015

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