Descriptor: "MESH: Injections, Intraperitoneal" - Searchworks@Jio Institute Digital Library Search Results

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26 results on '"MESH: Injections, Intraperitoneal"'

1. The tyrosine kinase inhibitor imatinib mesylate suppresses uric acid crystal-induced acute gouty arthritis in mice

Author: Dongmin Kang, Stephan Rogalla, Bianca Balbino, Riccardo Sibilano, Harini Raghu, Philipp Starkl, Christopher H. Contag, Stephen J. Galli, Steven Sensarn, William H. Robinson, Laurent L. Reber, Jeremy Sokolove, Mindy Tsai, Nicolas Gaudenzio, Department of Pathology [Stanford], Stanford Medicine, Stanford University-Stanford University, Sean N. Parker Center for Allergy and Asthma Research [Stanford], Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC), Stanford School of Medicine [Stanford], Molecular Imaging Program at Stanford (MIPS), EWHA Womans University (EWHA), Veterans Affairs Palo Alto Healthcare System [Palo Alto, CA, États-Unis], Department of Microbiology and Immunology [Stanford], L.L.R. acknowledges support from the Arthritis National Research Foundation (ANRF), National Institutes of Health grant K99 AI110645, the European Commission (Marie Skłodowska-Curie Individual Fellowship H2020-MSCA-IF-2014 656086) and the Institut National de la Santé et de la Recherche Médicale (INSERM), P.S. was supported by a Max Kade Fellowship of the Max Kade Foundation and the Austrian Academy of Sciences and a Schroedinger Fellowship of the Austrian Science Fund (FWF): J3399-B21, B.B. was supported by a stipend from the Pasteur - Paris University (PPU) International Ph.D. Program, R.S. was supported by the Lucile Packard Foundation for Children’s Health and the Stanford NIH/NCRR CTSA award number UL1 RR025744, N.G. was the recipient of a fellowship from the French 'Fondation pour la Recherche Médicale FRM', S.R. was supported in part by the George Will Foundation, C.H.C. acknowledges the Chambers Family Foundation Fund for Excellence in Pediatric Research, and the Child Health Research Institute at Stanford for their generous support, S.J.G. acknowledges support from National Institutes of Health grants U19 AI104209, NS 080062, and R01 AR067145 and the Department of Pathology, Stanford University School of Medicine., We thank Dr. Rajadas and the Stanford Biomaterials and Advanced Drug Delivery (BioADD) Laboratory core for the production of the imatinib-loaded PLGA nanoparticles., HAL UPMC, Gestionnaire, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Veterans Affairs Palo Alto Healthcare System
Subjects: 0301 basic medicine, Gout, MESH: Protein Kinase Inhibitors / administration & dosage, lcsh:Medicine, Arthritis, MESH: Uric Acid / chemistry, Pharmacology, Pathology and Laboratory Medicine, Mouse models, Tyrosine-kinase inhibitor, Mice, chemistry.chemical_compound, 0302 clinical medicine, Medicine and Health Sciences, Nanotechnology, MESH: Animals, lcsh:Science, Musculoskeletal System, Immune Response, Routes of Administration, MESH: Crystallization, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Multidisciplinary, Arthritis, Gouty, Animal Models, Protein-Tyrosine Kinases, 3. Good health, Experimental Organism Systems, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Rheumatoid arthritis, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Physical Sciences, Imatinib Mesylate, Legs, Engineering and Technology, Anatomy, Crystallization, Tyrosine kinase, Injections, Intraperitoneal, MESH: Injections, Intraperitoneal, Research Article, medicine.drug, medicine.medical_specialty, Materials by Structure, medicine.drug_class, Inflammatory Diseases, Materials Science, Immunology, Intraperitoneal injections, MESH: Imatinib Mesylate / administration & dosage, Research and Analysis Methods, Crystals, 03 medical and health sciences, MESH: Protein-Tyrosine Kinases / antagonists & inhibitors, Model Organisms, Signs and Symptoms, Rheumatology, MESH: Imatinib Mesylate / pharmacology, Diagnostic Medicine, MESH: Mice, Inbred C57BL, Internal medicine, medicine, Animals, Protein Kinase Inhibitors, MESH: Mice, 030203 arthritis & rheumatology, Inflammation, MESH: Arthritis, Gouty / prevention & control, business.industry, lcsh:R, Limbs (Anatomy), Ankles, Biology and Life Sciences, Imatinib, medicine.disease, MESH: Uric Acid / adverse effects, MESH: Protein Kinase Inhibitors / pharmacology, Uric Acid, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, Imatinib mesylate, chemistry, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Uric acid, Nanoparticles, lcsh:Q, business
Abstract: International audience; Gouty arthritis is caused by the deposition of monosodium urate (MSU) crystals in joints. Despite many treatment options for gout, there is a substantial need for alternative treatments for patients unresponsive to current therapies. Tyrosine kinase inhibitors have demonstrated therapeutic benefit in experimental models of antibody-dependent arthritis and in rheumatoid arthritis in humans, but to date, the potential effects of such inhibitors on gouty arthritis has not been evaluated. Here we demonstrate that treatment with the tyrosine kinase inhibitor imatinib mesylate (imatinib) can suppress inflammation induced by injection of MSU crystals into subcutaneous air pouches or into the ankle joint of wild type mice. Moreover, imatinib treatment also largely abolished the lower levels of inflammation which developed in IL-1R1-/- or KitW-sh/W-sh mice, indicating that this drug can inhibit IL-1-independent pathways, as well as mast cell-independent pathways, contributing to pathology in this model. Imatinib treatment not only prevented ankle swelling and synovial inflammation when administered before MSU crystals but also diminished these features when administrated after the injection of MSU crystals, a therapeutic protocol more closely mimicking the clinical situation in which treatment occurs after the development of an acute gout flare. Finally, we also assessed the efficiency of local intra-articular injections of imatinib-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles in this model of acute gout. Treatment with low doses of this long-acting imatinib:PLGA formulation was able to reduce ankle swelling in a therapeutic protocol. Altogether, these results raise the possibility that tyrosine kinase inhibitors might have utility in the treatment of acute gout in humans.
Published: 2017

2. Erythropoietin Restores C-Fiber Function and Prevents Pressure Ulcer Formation in Diabetic Mice

Author: James Javellaud, Vincent Sarrazy, Nicole Oudart, L. Botelle, Loriane Gourloi, Claire Demiot, Jean-Michel Achard, Homéostasie Cellulaire et Pathologies (HCP), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Laboratoire de Chimie des Substances Naturelles (LCSN), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), and Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Vasodilation, Pharmacology, Biochemistry, MESH: Dose-Response Relationship, Drug, MESH: Recombinant Proteins, Mice, 0302 clinical medicine, MESH: Diabetes Mellitus, Experimental, MESH: Animals, Skin, MESH: Treatment Outcome, Pressure Ulcer, 0303 health sciences, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Recombinant Proteins, 3. Good health, Dose–response relationship, Treatment Outcome, medicine.anatomical_structure, Nociception, Anesthesia, Injections, Intraperitoneal, MESH: Injections, Intraperitoneal, medicine.drug, MESH: Pressure Ulcer, Endothelium, Dermatology, Streptozocin, Diabetes Mellitus, Experimental, Magnetics, 03 medical and health sciences, MESH: Skin, Diabetes mellitus, MESH: Nerve Fibers, Unmyelinated, medicine, Animals, MESH: Magnetics, MESH: Erythropoietin, Erythropoietin, MESH: Mice, Molecular Biology, 030304 developmental biology, Nerve Fibers, Unmyelinated, Dose-Response Relationship, Drug, business.industry, MESH: Streptozocin, Cell Biology, Neurovascular bundle, Streptozotocin, medicine.disease, MESH: Male, Disease Models, Animal, MESH: Disease Models, Animal, business, 030217 neurology & neurosurgery
Abstract: International audience; Pressure-induced vasodilatation (PIV), a cutaneous physiological neurovascular (C-fiber/endothelium) mechanism, is altered in diabetes and could possibly contribute to pressure ulcer development. We wanted to determine whether recombinant human erythropoietin (rhEPO), which has protective neurovascular effects, could prevent PIV alteration and pressure ulcer formation. We developed a skin pressure ulcer model in mice by applying two magnetic plates to the dorsal skin. This induced significant stage 2 ulcers (assessed visually and histologically) in streptozotocin-treated mice with 8 weeks of diabetes compared with very few in controls. Control and streptozotocin mice received either no treatment or systematic rhEPO (3,000 UI kg(-1) intraperitoneally, twice a week) during the last 2 weeks of diabetes. After 8 weeks of diabetes, we assessed ulcer development, PIV, endothelium-dependent vasodilation, C-fiber-mediated nociception threshold, and skin innervation density. Pretreatment with rhEPO fully prevented ulcer development in streptozotocin mice and also fully restored C-fiber nociception, skin innervation density, and significantly improved PIV, but had no effect on endothelium-dependent vasodilation. Our finding that rhEPO treatment protects the skin against pressure-induced ulcers in diabetic mice encourages evaluation of the therapeutic potential for non-hematopoietic analogs of EPO in preventing neuropathic diabetic ulcers.
Published: 2011

3. Population Pharmacokinetics and Dosing Recommendations for Cisplatin during Intraperitoneal Peroperative Administration

Author: Xavier Pivot, Bruno Chauffert, Jean-Pierre Kantelip, Emmanuel Guardiola, Vincent Jullien, Bruno Heyd, Bernard Royer, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Pharmacologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Epilepsies de l'Enfant et Plasticité Cérébrale (U1129), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Service de chirurgie viscérale et digestive - Unité de transplantation hépatique, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( UR 3920) (PCVP / CARDIO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( EA 3920) (PCVP / CARDIO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Cochin-Saint Vincent de Paul, Epilepsies de l'Enfant et Plasticité Cérébrale ( U1129 ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'oncologie Médicale, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( PCVP / CARDIO ), Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) ( HOTE GREFFON ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( EA 3920) ( PCVP / CARDIO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université de Franche-Comté ( UFC ) -Université Bourgogne Franche-Comté [COMUE] ( UBFC ), and Saas, Philippe
Subjects: MESH: Combined Modality Therapy, MESH : Aged, MESH : Dose-Response Relationship, Drug, MESH : Models, Biological, MESH: Risk Assessment, 030226 pharmacology & pharmacy, MESH: Dose-Response Relationship, Drug, Intraoperative Period, MESH : Metabolic Clearance Rate, 0302 clinical medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Medicine, MESH : Female, Pharmacology (medical), MESH : Risk Assessment, Ovarian Neoplasms, MESH: Aged, Volume of distribution, education.field_of_study, MESH: Middle Aged, Middle Aged, MESH : Adult, MESH : Nonlinear Dynamics, Combined Modality Therapy, 3. Good health, MESH : Antineoplastic Agents, MESH: Nonlinear Dynamics, MESH: Ovarian Neoplasms, Area Under Curve, 030220 oncology & carcinogenesis, Toxicity, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH : Intraoperative Period, Risk assessment, Monte Carlo Method, Injections, Intraperitoneal, MESH: Injections, Intraperitoneal, Adult, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Metabolic Clearance Rate, MESH : Drug Administration Schedule, Population, Urology, Antineoplastic Agents, MESH: Monte Carlo Method, MESH: Drug Administration Schedule, Models, Biological, Risk Assessment, Drug Administration Schedule, MESH : Cisplatin, 03 medical and health sciences, Pharmacokinetics, Humans, MESH : Middle Aged, Dosing, education, Aged, MESH: Intraoperative Period, MESH: Metabolic Clearance Rate, Pharmacology, MESH : Injections, Intraperitoneal, MESH: Humans, Dose-Response Relationship, Drug, MESH : Ovarian Neoplasms, business.industry, MESH : Humans, MESH: Models, Biological, MESH: Adult, Nomogram, NONMEM, MESH : Monte Carlo Method, Nonlinear Dynamics, MESH: Cisplatin, MESH: Antineoplastic Agents, MESH: Area Under Curve, MESH : Area Under Curve, Cisplatin, MESH : Combined Modality Therapy, business, MESH: Female
Abstract: International audience; BACKGROUND: Ovarian cancer is the leading cause of gynaecological cancer-related death in Western countries. Intraperitoneal (IP) peroperative chemotherapy is an interesting therapeutic option. However, very few data are available regarding pharmacokinetics and especially population pharmacokinetics. PATIENTS AND METHODS: Thirty-one patients with advanced epithelial cancer classified as International Federation of Gynecology and Obstetrics stage IIIC were included in the study. Blood and IP samples were taken over a 24-hour period during and after IP treatment. Both total and ultrafiltered (Uf) platinum (Pt) concentrations were analysed using a population approach with nonlinear mixed-effects modelling (NONMEM) software. Improvement of the model with covariates was performed as well as assessment of the model using bootstrap and posterior visual predictive methods. RESULTS: Both IP fluid and serum pharmacokinetics were satisfactorily described with a three-compartment model for both Uf Pt and total Pt concentrations. The covariates were bodyweight for the IP volume of distribution in the Uf Pt model, and both IP and serum protein concentrations for the clearance from the central compartment in the total Pt model. A nomogram, based on the results of the Monte Carlo simulations, displays a dose recommendation regarding both the risk of renal toxicity and the potent efficacy of the treatment. A limited sampling strategy (LSS) allowing the estimation of potential risk of renal toxicity is also described. CONCLUSION: The pharmacokinetics of cisplatin during peroperative IP chemotherapy could be successfully fitted with the present model, which allowed a dosing strategy accompanied by an LSS to facilitate the follow-up of patients.
Published: 2009

4. Toxic Effects of Iterative Intraperitoneal Administration of Zinc Gluconate in Rats

Author: Laurence Touvard, Diane Agay, Richard Claeyssen, Yves Chancerelle, Josiane Denis, Josiane Arnaud, M Andriollo-Sanchez, Anne-Marie Roussel, Centre de Recherches du Service de Santé des Armées (CRSSA), Service de Santé des Armées, Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe de Recherche en management stratégique (Euristik), Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Laboratoire de Recherche Magellan, Université de Lyon-Université de Lyon-Institut d'Administration des Entreprises (IAE) - Lyon-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Institut d'Administration des Entreprises (IAE) - Lyon, Université de Lyon-Université de Lyon-Centre de Recherche Magellan, and Hamant, Sarah
Subjects: Male, 030309 nutrition & dietetics, medicine.medical_treatment, Pharmacology, Toxicology, MESH: Dose-Response Relationship, Drug, Feces, 0302 clinical medicine, Tissue Distribution, MESH: Animals, 030212 general & internal medicine, Saline, 0303 health sciences, MESH: Feces, MESH: Gluconates, General Medicine, MESH: Pancreas, 3. Good health, Dose–response relationship, Liver, Toxicity, Injections, Intraperitoneal, MESH: Injections, Intraperitoneal, medicine.medical_specialty, MESH: Rats, chemistry.chemical_element, Zinc, Gluconates, 03 medical and health sciences, Internal medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Rats, Wistar, MESH: Tissue Distribution, Copper levels, Adverse effect, Pancreas, Dose-Response Relationship, Drug, business.industry, Body Weight, MESH: Rats, Wistar, MESH: Male, Rats, MESH: Body Weight, Endocrinology, chemistry, Acute exposure, business, MESH: Liver
Abstract: International audience; Although zinc is an essential trace element involved in many physiological functions, toxicological data concerning acute exposure are scarce. The aim of our study was to determine the maximal iterative dose of zinc that can be administrated in rats without any adverse effect. Saline (control group) or zinc gluconate at 1, 2 or 4 mg/kg were intraperitoneally injected in animals daily during 7 days. The tolerance of zinc treatments was evaluated by the observation of clinical symptoms, haematological parameters and biochemistry, in relation to the zinc and copper levels in blood, liver, pancreas and faeces. We found no serious adverse effect within 1 week in rats injected intraperitoneally with 1 or 2 mg/kg/day of zinc gluconate, which tends to indicate that those doses could be useful in future therapeutic research. In contrast, the therapeutic treatment of adult rats with repeated intraperitoneal injections of a 4 mg/kg/day zinc dose should be cancelled, due to the occurrence of clinical adverse effects within a few days, as intraperitoneal local intolerance or major growth underdevelopment.
Published: 2008

5. Benefit of tianeptine and morphine in a transgenic model of familial amyotrophic lateral sclerosis

Author: Gérard Besson, Marc Savasta, M. Chritin, Département de neurologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Dynamique des Reseaux Neuronaux, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Collaboration, and Savasta, Marc
Subjects: Male, MESH: Thiazepines, Thiazepines, Disease, Antidepressive Agents, Tricyclic, Pharmacology, MESH: Analgesics, Opioid, medicine.disease_cause, Transgenic Model, Mice, 0302 clinical medicine, MESH: Animals, Tianeptine, Amyotrophic lateral sclerosis, MESH: Amyotrophic Lateral Sclerosis, MESH: Superoxide Dismutase, MESH: Treatment Outcome, 0303 health sciences, Mutation, Morphine, General Medicine, MESH: Recovery of Function, 3. Good health, Analgesics, Opioid, Survival Rate, Drug Combinations, Treatment Outcome, Neurology, Anesthesia, Injections, Intraperitoneal, MESH: Injections, Intraperitoneal, medicine.drug, Genetically modified mouse, MESH: Survival Rate, MESH: Mice, Transgenic, SOD1, Mice, Transgenic, 03 medical and health sciences, medicine, Animals, MESH: Mice, Pathological, 030304 developmental biology, MESH: Drug Combinations, Superoxide Dismutase, business.industry, Amyotrophic Lateral Sclerosis, Recovery of Function, medicine.disease, MESH: Male, MESH: Antidepressive Agents, Tricyclic, Disease Models, Animal, MESH: Morphine, Neurology (clinical), MESH: Disease Models, Animal, business, 030217 neurology & neurosurgery
Abstract: International audience; The familial form of amyotrophic lateral sclerosis (FALS) has been linked in some cases to dominant mutations in the gene encoding the Cu/Zn superoxide dismutase (SOD1) mutation. Transgenic mice bearing the G93A SOD1 mutation develop clinical symptoms and pathological features similar to those described in the human disease and represent a good model to explore the potential benefit of therapeutic agents. Using this animal model, we tested the efficacy of morphine and tianeptine treatments, separately and in association, on both disease progression and survival. Acute injection of either of them, administered daily and before the onset of the disease, significantly prolonged the survival of the transgenic mice.
Published: 2006

6. Intraperitoneal clearance as a potential biomarker of cisplatin after intraperitoneal perioperative chemotherapy: a population pharmacokinetic study

Author: Virginie Nerich, Sebastien Pili-Floury, Marielle Combe, Antoine Thiery-Vuillemin, Sylvain Onteniente, Damien Montange, Emmanuel Guardiola, Vincent Jullien, Bruno Chauffert, Patrice Muret, Xavier Pivot, Bernard Royer, Bruno Heyd, Delphine Delroeux, Jean-Pierre Kantelip, Sarah Piedoux, Elsa Kalbacher, Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Laboratoire de Pharmacologie Clinique et Toxicologie [CHRU Besancon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Service d'Oncologie Médicale [CHRU Besançon], Service de pharmacologie, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Saint-Vincent de Paul-Université Paris Descartes - Paris 5 (UPD5), Epilepsies de l'Enfant et Plasticité Cérébrale (U1129), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'oncologie chirurgicale, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service d'anesthésie et soins intensifs [CHRU Besançon], Pôle pharmaceutique [CHRU Besançon], Service d'oncologie, CHU Amiens-Picardie, Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Centre d'Investigation Clinique de Besançon ( CICB ), Etablissement Français du Sang Bourgogne Franche-Comté-Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Franche-Comté ( UFC ), Université de Franche-Comté ( UFC ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Laboratoire de Pharmacologie Clinique et Toxicologie [Besancon], Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz-Université de Franche-Comté ( UFC ), Service d'oncologie Médicale, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, CHU Cochin [AP-HP]-Hôpital Saint-Vincent de Paul-Université Paris Descartes - Paris 5 ( UPD5 ), Epilepsies de l'Enfant et Plasticité Cérébrale ( U1129 ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Service d'anesthésie et soins intensifs, Hôpital Jean Minjoz, Service de pharmacie, Saas, Philippe, and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Cancer Research, MESH : Aged, cisplatin, MESH : Models, Biological, Pharmacology, intraperitoneal perioperative chemotherapy, 030226 pharmacology & pharmacy, Intraoperative Period, MESH : Metabolic Clearance Rate, 0302 clinical medicine, population pharmacokinetics, Clinical Studies, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, Ovarian Neoplasms, Volume of distribution, MESH: Aged, education.field_of_study, MESH: Middle Aged, MESH: Peritoneum, MESH : Chemotherapy, Adjuvant, Middle Aged, MESH : Adult, 3. Good health, MESH : Antineoplastic Agents, MESH: Ovarian Neoplasms, Epinephrine, Oncology, Chemotherapy, Adjuvant, MESH: Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Toxicity, biomarker, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH : Intraoperative Period, Peritoneum, Injections, Intraperitoneal, MESH: Injections, Intraperitoneal, medicine.drug, Adult, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Metabolic Clearance Rate, MESH: Epinephrine, MESH : Drug Administration Schedule, Population, Urology, Antineoplastic Agents, MESH: Drug Administration Schedule, Models, Biological, Drug Administration Schedule, MESH : Cisplatin, 03 medical and health sciences, Pharmacokinetics, medicine, Humans, MESH : Middle Aged, education, MESH : Peritoneum, Aged, Cisplatin, MESH: Intraoperative Period, MESH: Metabolic Clearance Rate, MESH : Injections, Intraperitoneal, MESH: Humans, MESH : Ovarian Neoplasms, business.industry, MESH : Humans, MESH: Models, Biological, MESH: Biological Markers, MESH: Adult, medicine.disease, NONMEM, MESH : Biological Markers, MESH: Cisplatin, MESH : Epinephrine, MESH: Antineoplastic Agents, Ovarian cancer, business, MESH: Female, Biomarkers
Abstract: International audience; BACKGROUND: Intraperitoneal (IP) perioperative chemotherapy with cisplatin is an interesting option in ovarian cancer treatment. A combination of cisplatin with IP epinephrine (already shown to improve IP and decrease systemic platinum (Pt) exposure) was evaluated using a population pharmacokinetic analysis. METHODS: Data from 55 patients treated with cisplatin-based IP perioperative chemotherapy with (n=26) or without (n=29) epinephrine were analysed using NONMEM. RESULTS: Epinephrine halves clearance between peritoneum and serum (IPCL) and increases the Pt central volume of distribution, IP exposure and penetration in tissue. IPCL has a better predictive value than any other parameter with respect to renal toxicity. CONCLUSION: This confirms that IPCL could be useful in assessing renal toxicity. As IPCL is also linked to tissue penetration and IP exposure, it may be proposed as biomarker. In addition to a Bayesian estimation, we propose a single-sample calculation-way to assess it. Prospective studies are needed to validate IPCL as a biomarker in this context.
Published: 2012

7. Experimental Meningococcal Sepsis in Congenic Transgenic Mice Expressing Human Transferrin

Author: Corinne Ruckly, Muhamed-Kheir Taha, Eva Hong, Marek Szatanik, Dario Giorgini, Katarzyna Jopek, Morgan Ledroit, Marie-Anne Nicola, Ala-Eddine Deghmane, Infections Bactériennes Invasives, Institut Pasteur [Paris], Imagerie Dynamique (Plate-Forme) (PFID), The work was supported exclusively by the Institut Pasteur with no external funding., and Institut Pasteur [Paris] (IP)
Subjects: Bacterial Diseases, Viral Diseases, Critical Care and Emergency Medicine, Mouse, Microarrays, Colony Count, Microbial, Gene Expression, lcsh:Medicine, Neisseria meningitidis, medicine.disease_cause, MESH: Meningococcal Infections, Mice, Molecular Cell Biology, MESH: Animals, lcsh:Science, MESH: Sepsis, Animal Management, chemistry.chemical_classification, Inhalation Exposure, Mice, Inbred BALB C, 0303 health sciences, MESH: Cytokines, Multidisciplinary, Transferrin, Acute-phase protein, Brain, Agriculture, Animal Models, MESH: Gene Expression Regulation, Bacterial Pathogens, 3. Good health, Infectious Diseases, Influenza A virus, MESH: Survival Analysis, Medicine, Cytokines, MESH: Inhalation Exposure, Transgenic Animals, Injections, Intraperitoneal, MESH: Transferrin, MESH: Injections, Intraperitoneal, Research Article, MESH: Mice, Transgenic, MESH: Influenza A virus, Congenic, MESH: Mice, Inbred BALB C, Mice, Transgenic, Biology, Meningococcal disease, Microbiology, MESH: Neisseria meningitidis, Sepsis, Mice, Congenic, 03 medical and health sciences, MESH: Brain, Model Organisms, Immune system, MESH: Mice, Congenic, medicine, Animals, Humans, MESH: Mice, MESH: Colony Count, Microbial, 030304 developmental biology, Innate immune system, MESH: Humans, 030306 microbiology, lcsh:R, Computational Biology, medicine.disease, Survival Analysis, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Influenza, Meningococcal Infections, Gene Expression Regulation, chemistry, Immunology, Meningoccal Septicemia, lcsh:Q
Abstract: International audience; Severe meningococcal sepsis is still of high morbidity and mortality. Its management may be improved by an experimental model allowing better understanding of its pathophysiology. We developed an animal model of meningococcal sepsis in transgenic BALB/c mice expressing human transferrin. We studied experimental meningococcal sepsis in congenic transgenic BALB/c mice expressing human transferrin by transcriptional profiling using microarray analysis of blood and brain samples. Genes encoding acute phase proteins, chemokines and cytokines constituted the largest strongly regulated groups. Dynamic bioluminescence imaging further showed high blood bacterial loads that were further enhanced after a primary viral infection by influenza A virus. Moreover, IL-1 receptor-associated kinase-3 (IRAK-3) was induced in infected mice. IRAK-3 is a negative regulator of Toll-dependant signaling and its induction may impair innate immunity and hence result in an immunocompromised state allowing bacterial survival and systemic spread during sepsis. This new approach should enable detailed analysis of the pathophysiology of meningococcal sepsis and its relationships with flu infection.
Published: 2011

8. Acute food deprivation reduces expression of diazepam-binding inhibitor, the precursor of the anorexigenic octadecaneuropeptide ODN, in mouse glial cells

Author: Schouft, Marie-Thérèse, Fontaine, Marc, Scalbert, Elisabeth, Malagon, Maria, Gandolfo, Pierrick, Desrues, Laurence, Cellier, Eric, Decker, Annick, Clerens, Stefan, Vandesande, Frans, Do-Rego, C., Beauvillain, C., Baroncini, Marc, Balment, Richard, Dujardin, Cynthia, Tollemer, Helene, BRUZZONE, FEDERICA, Tollemer, Hélène, Do-Régo, Jean, Simonnet, Guy, VALLARINO, MAURO, Beauvillain, Jean, Costentin, Jean, Do-Régo, Jean-Claude, Beauvillain, Jean-Claude, Chartrel, C, Alvear-Perez, P, Iturrioz, X., Reaux-Le Goazigo, A., Audinot, V., Chomarat, C, Coge, C, Nosjean, O., Rodriguez, M., Galizzi, J., Goazigo, R., Chomarat, P., Coge, F., Chartrel, Nicolas, Alonzeau, Jessy, Alexandre, David, Jeandel, Jean, Alvear-Perez, Rodrigo, Boutin, Jean, Anouar, Youssef, Llorens-Cortes, Catherine, Jeandel, Lydie, Carlier, Ludovic, Ségalas-Milazzo, Isabelle, Guilhaudis, Laure, Oulyadi, Hassan, Davoust, Daniel, Dubessy, Christophe, Scalbert, Elizabeth, Pfeiffer, Bruno, Renard, Pierre, Lihrmann, Isabelle, Pacaud, Pierre, Chevrier, Lucie, De Brevern, Alexandre, Hernandez, Eva, Guedj, Anne Marie, de Roux, Nicolas, Cholez, V, Debuysscher, V, Bourgeais, B, Boudot, B, Tron, F., Brassart, B., Regnier, A., Bissac, E, Pecnard, E, Gouilleux, F., Lassoued, K, Gouilleux-Gruart, V, Cholez, E, Bourgeais, J, Boudot, C., Gouilleux, V, Chuquet, Julien, Lecrux, Clotilde, Chatenet, David, Chazalviel, Laurent, Roussel, Simon, MacKenzie, Eric, Touzani, Omar, Tonon, M.C, Li, S., Leprince, J�r�me, Tonon, M.C., Compère, M, Lanfray, D, Castel, Hélène, Morin, M., Leprince, Jérôme, Dureuil, B, Vaudry, Hubert, Pelletier, G., Tonon, Marie-Christine, Compère, V., Morin, F., Dureuil, D, Vaudry, V, inconnu, Inconnu, Neuroendocrinologie cellulaire et moléculaire, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Différenciation et communication neuronale et neuroendocrine (DC2N), Chercheur indépendant, Laboratoire de l'intégration, du matériau au système (IMS), Centre National de la Recherche Scientifique (CNRS)-Institut Polytechnique de Bordeaux-Université Sciences et Technologies - Bordeaux 1, University of Córdoba [Córdoba], Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc - U837 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille 2 - Faculté de Médecine, UMR 5287, Homéostasie-Allostasie-Pathologie-Réhabilitation, Centre National de la Recherche Scientifique (CNRS), Neuropsycho-pharmacologie expérimentale, Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Institut de la Vision, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique et Physiologie Intégratives de l'Arbre Fruitier et Forestier (PIAF), Institut National de la Recherche Agronomique (INRA)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Centre National de la Recherche Scientifique (CNRS), Neuropeptides centraux et régulations hydrique et cardiovasculaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherches Servier, Centre de Recherches de Croissy, ESPE de l'Académie d'Amiens, Chimie Organique et Bioorganique : Réactivité et Analyse (COBRA), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie Organique Fine (IRCOF), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Equipe de Chimie Organique et Biologie Structurale (ECOBS), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA), Université Henri Poincaré - Nancy 1 (UHP), Institut de recherches Servier (INSTITUT DE RECHERCHES SERVIER), INSTITUT SERVIER, Les Laboratoires SERVIER, Institut de Recherche Servier, Institut du thorax, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie et neuroprotection des atteintes du cerveau en développement, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bioinformatique génomique et moléculaire ((U 726)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Service des Maladies Métaboliques et Endocriniennes, Hôpital Universitaire Carémeau [Nîmes], Neuroprotection du Cerveau en Développement / Promoting Research Oriented Towards Early Cns Therapies (PROTECT), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Fédératif de Recherches Multidisciplinaires sur les Peptides (IFRMP 23), Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Henri Becquerel-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), STMicroelectronics, Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Matrice extracellulaire et régulations cellulaires (MERC), Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), Institut Armand Frappier (INRS-IAF), Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS), Neurodégénérescence : modèles et stratégies thérapeutiques (NMST), Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Aix-Marseille Université - Faculté de pharmacie (AMU PHARM), Aix Marseille Université (AMU), IRCELYON-Ingéniérie, du matériau au réacteur (ING), Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Télécom SudParis (TSP), Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille 2 - Faculté de Médecine -Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [APHP], CHU Rouen, Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-CRLCC Henri Becquerel-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre interdisciplinaire de recherche en biologie (CIRB), Collège de France (CdF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-PSL Research University (PSL)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-PSL Research University (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Chimie Organique Fine (IRCOF), Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université Le Havre Normandie (ULH), Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), and Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Leptin, Male, Transcription, Genetic, MESH: Sequence Homology, Amino Acid, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MESH: Receptors, G-Protein-Coupled, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, MESH: Neuropeptides, Energy homeostasis, MESH: Down-Regulation, MESH: Ependyma, Mice, 0302 clinical medicine, Endocrinology, Lateral Ventricles, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Insulin, MESH: Animals, MESH: Proline-Rich Protein Domains, MESH: Peptide Fragments, MESH: Lateral Ventricles, Diazepam Binding Inhibitor, 2. Zero hunger, 0303 health sciences, MESH: Ranidae, MESH: Receptors, Kisspeptin-1, Fasting, medicine.anatomical_structure, Hypothalamus, Neuroglia, MESH: Neuroglia, Ependyma, Diazepam binding inhibitor, Injections, Intraperitoneal, MESH: Injections, Intraperitoneal, Protein Binding, MESH: Protein Transport, medicine.medical_specialty, MESH: Rats, Central nervous system, Down-Regulation, Neuropeptide, MESH: Fasting, MESH: Insulin, Biology, 03 medical and health sciences, Internal medicine, medicine, Animals, MESH: Protein Binding, Molecular Biology, MESH: Mice, Third Ventricle, MESH: RNA, Messenger, 030304 developmental biology, MESH: Transcription, Genetic, Neuropeptides, MESH: Time Factors, MESH: Rats, Wistar, MESH: Leptin, MESH: Hypothalamus, Peptide Fragments, MESH: Male, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, MESH: Diazepam Binding Inhibitor, 030217 neurology & neurosurgery, MESH: Third Ventricle
Abstract: In the central nervous system of mammals, the gene encoding diazepam-binding inhibitor (DBI) is exclusively expressed in glial cells. Previous studies have shown that central administration of a DBI processing product, the octadecaneuropeptide ODN, causes a marked inhibition of food consumption in rodents. Paradoxically, however, the effect of food restriction on DBI gene expression has never been investigated. Here, we show that in mice, acute fasting dramatically reduces DBI mRNA levels in the hypothalamus and the ependyma bordering the third and lateral ventricles. I.p. injection of insulin, but not of leptin, selectively stimulated DBI expression in the lateral ventricle area. These data support the notion that glial cells, through the production of endozepines, may relay peripheral signals to neurons involved in the central regulation of energy homeostasis.
Published: 2010

9. Intraoperative chemotherapy with cisplatin and epinephrine after cytoreductive surgery in patients with recurrent ovarian cancer: a phase I study

Author: Martin Demarchi, Laurent Benoit, Françoise Mayer, Emmanuel Guardiola, Xavier Pivot, Hervé Tixier, Bernard Royer, Bruno Chauffert, Delphine Delroeux, Marielle Combe, Guy Magnin, Bruno Heyd, Sylvain Causeret, Service d'oncologie Médicale, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Service de chirurgie viscérale et digestive - Unité de transplantation hépatique, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Hôpital Jean Minjoz, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Service de Chirurgie Digestive, Cancérologique, Générale, Endocrinienne et Urgences (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Service d'anesthésie - réanimation chirurgicale [CHU de Dijon], Service de Gynécologie Obstétrique, Médecine Foetale et Stérilité Conjugale - Chirurgie Gynécologie et Oncologique [CHU de Dijon], Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), and Saas, Philippe
Subjects: Cancer Research, MESH : Antineoplastic Combined Chemotherapy Protocols, medicine.medical_treatment, MESH : Heart Injuries, MESH : Aged, MESH: Intraoperative Care, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Pharmacology (medical), MESH : Female, MESH: Treatment Outcome, Ovarian Neoplasms, MESH: Aged, 0303 health sciences, MESH: Middle Aged, MESH : Neoplasm Recurrence, Local, Area under the curve, MESH : Intraoperative Care, Middle Aged, MESH : Adult, 3. Good health, MESH: Ovarian Neoplasms, MESH: Antineoplastic Combined Chemotherapy Protocols, Treatment Outcome, Epinephrine, Oncology, 030220 oncology & carcinogenesis, Anesthesia, Toxicity, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, France, MESH: Neoplasm Recurrence, Local, Injections, Intraperitoneal, MESH: Injections, Intraperitoneal, medicine.drug, Adult, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Epinephrine, Urology, Peritonitis, MESH : Treatment Outcome, MESH : Cisplatin, 03 medical and health sciences, medicine, Humans, MESH : Middle Aged, Adverse effect, MESH : France, Aged, 030304 developmental biology, Pharmacology, Cisplatin, Chemotherapy, Intraoperative Care, MESH: Humans, MESH : Injections, Intraperitoneal, business.industry, MESH : Ovarian Neoplasms, MESH : Humans, MESH: Adult, medicine.disease, MESH: France, MESH: Heart Injuries, Heart Injuries, MESH: Cisplatin, MESH : Epinephrine, Neoplasm Recurrence, Local, business, Ovarian cancer, MESH: Female
Abstract: International audience; BACKGROUND: Intraperitoneal (i.p.) epinephrine was shown to increase the accumulation of i.p. cisplatin in tumours, and thus its antitumour effect in a model of peritoneal carcinomatosis in rats. METHODS: To determine the tolerance to i.p. epinephrine with cisplatin, 18 patients with recurrent ovarian carcinoma were intraoperatively treated in this phase 1 study. After maximal cytoreductive surgery, the peritoneal cavity was filled twice for 1 h with 30 mg/l of cisplatin and increasing concentrations of epinephrine (0, 1, 2, 3 mg/l) in 3 l of saline solution at 37 degrees C. RESULTS: No deaths occurred. Three patients were treated at each of the 0, 1 and 2 mg/l epinephrine levels without adverse events. Two of the three patients who received 3 mg/l epinephrine experienced cardiac intolerance. Six additional patients received 2 mg/l of epinephrine without toxicity. A relationship between the serum concentration of epinephrine and occurrence of cardiac toxicity was established. A 60% decrease in serum area under the curve of platinum was calculated in patients receiving i.p. epinephrine compared with i.p. cisplatin alone. Renal toxicity from cisplatin was not increased by epinephrine. No haematological or neurological toxicity was recorded. The other grade 3-4 adverse events [thromboembolism (5), peritonitis (1), abdominal bleeding (1), bowel fistula (1)] occurred as often as usually reported for this heavy surgical procedure. CONCLUSION: The combination of i.p. epinephrine with cisplatin as intraoperative chemotherapy after optimal cytoreductive surgery is feasible. The recommended concentration for further studies is 2 mg/l for i.p. epinephrine.
Published: 2010

10. Overexpressed or intraperitoneally injected human transferrin prevents photoreceptor degeneration in rd10 mice

Author: Picard, Émilie, Jonet, Laurent, Sergeant, Claire, Vesvres, Marie-Hélène, Behar-Cohen, Francine, Courtois, Yves, Jeanny, Jean-Claude, Picard, Emilie, Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Chimie Nucléaire Analytique et Bio-environnementale (CNAB), Université Sciences et Technologies - Bordeaux 1-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université Sciences et Technologies - Bordeaux 1 (UB)-Centre National de la Recherche Scientifique (CNRS)
Subjects: genetic structures, MESH: Retinal Degeneration, Iron, MESH: Biological Transport, [SDV]Life Sciences [q-bio], Animals, Biological Transport/drug effects, Disease Models, Animal, Electron Probe Microanalysis, Humans, Injections, Intraperitoneal, Iron/metabolism, Mice, Retina/drug effects, Retina/metabolism, Retinal Cone Photoreceptor Cells/drug effects, Retinal Cone Photoreceptor Cells/metabolism, Retinal Degeneration/drug therapy, Retinal Degeneration/pathology, Retinal Rod Photoreceptor Cells/drug effects, Retinal Rod Photoreceptor Cells/metabolism, Spectrometry, X-Ray Emission, Transferrin/administration & dosage, Transferrin/pharmacology, Retina, Retinal Rod Photoreceptor Cells, MESH: Electron Probe Microanalysis, MESH: Animals, MESH: Mice, MESH: Retinal Rod Photoreceptor Cells, MESH: Iron, MESH: Humans, MESH: Retina, Retinal Degeneration, Transferrin, Biological Transport, MESH: Spectrometry, X-Ray Emission, [SDV] Life Sciences [q-bio], MESH: Retinal Cone Photoreceptor Cells, Retinal Cone Photoreceptor Cells, sense organs, MESH: Disease Models, Animal, MESH: Transferrin, MESH: Injections, Intraperitoneal, Research Article
Abstract: International audience; Purpose: Retinal degeneration has been associated with iron accumulation in age-related macular degeneration (AMD), and in several rodent models that had one or several iron regulating protein impairments. We investigated the iron concentration and the protective role of human transferrin (hTf) in rd10 mice, a model of retinal degeneration.Methods: The proton-induced X-ray emission (PIXE) method was used to quantify iron in rd10 mice 2, 3, and 4 weeks after birth. We generated mice with the β-phosphodiesterase mutation and hTf expression by crossbreeding rd10 mice with TghTf mice (rd10/hTf mice). The photoreceptor loss and apoptosis were evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling in 3-week-old rd10/hTf mice and compared with 3-week-old rd10 mice. The neuroprotective effect of hTf was analyzed in 5-day-old rd10 mice treated by intraperitoneal administration with hTf for up to 25 days. The retinal hTf concentrations and the thickness of the outer nuclear layer were quantified in all treated mice at 25 days postnatally.Results: PIXE analysis demonstrated an age-dependent iron accumulation in the photoreceptors of rd10 mice. The rd10/hTf mice had the rd10 mutation, expressed high levels of hTf, and showed a significant decrease in photoreceptor death. In addition, rd10 mice intraperitoneally treated with hTf resulted in the retinal presence of hTf and a dose-dependent reduction in photoreceptor degeneration.Conclusions: Our results suggest that iron accumulation in the retinas of rd10 mutant mice is associated with photoreceptor degeneration. For the first time, the enhanced survival of cones and rods in the retina of this model has been demonstrated through overexpression or systemic administration of hTf. This study highlights the therapeutic potential of Tf to inhibit iron-induced photoreceptor cell death observed in degenerative diseases such as retinitis pigmentosa and age-related macular degeneration.
Published: 2010

11. Intra-operative intra-peritoneal chemotherapy with cisplatin in patients with peritoneal carcinomatosis of ovarian cancer

Author: Delphine Delroeux, Emmanuel Guardiola, Xavier Pivot, Veronique Lorgis, Ulrich Stein, Bernard Royer, Bruno Chauffert, Marielle Combe, Bruno Heyd, Martin Demarchi, Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de chirurgie viscérale et digestive - Unité de transplantation hépatique, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service d'anesthésie - réanimation, Laboratoire de Pharmacologie Clinique et Toxicologie [CHRU Besancon], Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, and Saas, Philippe
Subjects: Oncology, medicine.medical_treatment, MESH: Intraoperative Care, Carboplatin, chemistry.chemical_compound, Peritoneal Neoplasm, 0302 clinical medicine, Technical Innovations, Surgical oncology, MESH: Carboplatin, Antineoplastic Combined Chemotherapy Protocols, MESH: Peritoneal Neoplasms, 030212 general & internal medicine, Peritoneal Neoplasms, MESH: Treatment Outcome, Ovarian Neoplasms, MESH: Aged, MESH: Middle Aged, MESH: Neoplasm Staging, Middle Aged, Debulking, Prognosis, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, MESH: Cystadenocarcinoma, Serous, 3. Good health, MESH: Ovarian Neoplasms, MESH: Antineoplastic Combined Chemotherapy Protocols, Treatment Outcome, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Carcinoma, Endometrioid, MESH: Neoplasm Recurrence, Local, Injections, Intraperitoneal, MESH: Injections, Intraperitoneal, medicine.drug, Adult, medicine.medical_specialty, Paclitaxel, [SDV.IMM] Life Sciences [q-bio]/Immunology, lcsh:Surgery, lcsh:RC254-282, MESH: Prognosis, 03 medical and health sciences, Internal medicine, medicine, Humans, MESH: Paclitaxel, Aged, Neoplasm Staging, Cisplatin, Chemotherapy, Intraoperative Care, MESH: Humans, business.industry, Cancer, MESH: Adult, lcsh:RD1-811, medicine.disease, Surgery, Cystadenocarcinoma, Serous, chemistry, MESH: Carcinoma, Endometrioid, MESH: Cisplatin, Chemotherapy, Cancer, Regional Perfusion, Feasibility Studies, MESH: Chemotherapy, Cancer, Regional Perfusion, Neoplasm Recurrence, Local, business, Ovarian cancer, MESH: Feasibility Studies, MESH: Female
Abstract: Background Intra-peritoneal (i.p.) chemotherapy is an encouraging treatment option for ovarian cancer with peritoneum involvement in addition with intravenous (i.v.) chemotherapy. Intra-operative i.p. chemotherapy is an interesting method of administration by enhancing the diffusion of chemotherapy. This study had assessed the feasibility of intra-operative i.p. chemotherapy in patients with peritoneal carcinoma of ovarian cancer. Methods From January 2003 to February 2006, 47 patients with stage III ovarian cancer were treated with standard paclitaxel carboplatin intravenous chemotherapy and debulking surgery with intra-operative i.p. chemotherapy. After optimal cytoreductive surgery, defined by no unresectable residual disease > 1 cm, i.p. chemotherapy was performed during surgery. The peritoneal cavity was filled by 3 litres of isotonic saline pre-heated at 37 degrees and 90 mg of cisplatin. The sequence was repeated twice during 2 hours based on previous published studies which optimized the cisplatin dosage and exposure duration. Optimal diffusion was obtained by stirring by hands during the 2 hours. Results Median age was 59.6 years. No severe haematological or non-haematological toxicity induced by intra operative i.p. chemotherapy was reported. No patient died due to the complications of surgery or the i.p. chemotherapy. No neurotoxicity occurred, and one patients had renal impairment. Conclusion This study demonstrates the feasibility of intra-operative i.p. chemotherapy with cisplatin after optimal resection of peritoneal tumor nodules. Further randomized trials are planned to investigate the clinical benefit of this therapeutic modality.
Published: 2009

12. Cocaine-induced reinstatement in rats: evidence for a critical role of cocaine stimulus properties

Author: Martine Cador, Ronald Keiflin, Elsa Isingrini, Centre Neurosciences intégratives et Cognition (INCC - UMR 8002), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Aquitaine Institute of Cognitive and Integrative Neurosciences, and Université de Bordeaux (UB)
Subjects: Male, [SDV]Life Sciences [q-bio], MESH: Mental Recall, Pharmacology, Stimulus Salience, MESH: Association Learning, Extinction, Psychological, MESH: Appetitive Behavior, MESH: Dose-Response Relationship, Drug, Discrimination Learning, 0302 clinical medicine, Cocaine, Operant response, MESH: Animals, Food pellet, Discrimination learning, Sensitization, 2. Zero hunger, Appetitive Behavior, digestive, oral, and skin physiology, food and beverages, MESH: Motor Activity, medicine.anatomical_structure, Anesthesia, Incentive salience, Psychology, Injections, Intraperitoneal, MESH: Injections, Intraperitoneal, MESH: Rats, MESH: Motivation, Motor Activity, Stimulus (physiology), MESH: Central Nervous System Stimulants, 03 medical and health sciences, MESH: Cocaine, medicine, Animals, Rats, Wistar, Motivation, Dose-Response Relationship, Drug, fungi, Association Learning, MESH: Rats, Wistar, MESH: Extinction, Psychological, MESH: Discrimination Learning, MESH: Male, Rats, 030227 psychiatry, Locomotor sensitization, Mental Recall, Central Nervous System Stimulants, 030217 neurology & neurosurgery
Abstract: The exact behavioral nature of drug-induced reinstatement of drug seeking is still debated. As an incentive, the drug can have general facilitatory influences on appetitive behaviors. As an interoceptive stimulus, the drug can acquire discriminative properties and control behavior. This study assessed the relative contribution of the incentive versus discriminative properties of cocaine in food-seeking reinstatement. In Experiment 1, eight groups of rats were trained to press a lever for food pellets and experienced cocaine (0, 5, 10, or 15 mg/kg; i.p.), either during the operant conditioning sessions or 4 h after, in another environment without food access. In Experiment 2, to dissociate the role of the operant response per se from the consummatory response, two groups of rats experienced food consumption under cocaine (10 mg/kg; i.p.) either during operant conditioning sessions or during alternate sessions of free access to the food. Then, for both experiments, food pellets were withheld and cocaine injections ceased (extinction). The reinstating effects of noncontingent cocaine (10 mg/kg; i.p.) and food pellet delivery were assessed. Locomotor activity was recorded to probe expression of behavioral sensitization. Cocaine reinstated lever pressing only in rats having previously performed the operant responses under cocaine. In contrast, food pellet delivery reinstated lever pressing independently of rats’ history with cocaine. Locomotor sensitization was evidenced for all cocaine-pre-exposed rats, dissociating sensitization from reinstatement. When present during operant conditioning, the stimulus “cocaine” acquires conditioned properties which can then promote reinstatement of the extinguished behavior.
Published: 2008

13. Four disulfide-bridged scorpion beta neurotoxin CssII: heterologous expression and proper folding in vitro

Author: Cestèle, Sandrine, Estrada, Georgina, Garcia, Blanca, Schiavon, Emanuele, Ortiz, Ernesto, Cestele, Sandrine, Wanke, Enzo, Possani, Lourival, Corzo, Gerardo, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología-Universidad Nacional Autónoma de México (UNAM), Dipartimento di Biotecnologie e Bioscienze, Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute Bioclon SA, Conacyt-MOR-2004-C02-002, DGAPA IN226006, MIUR-PRIN2005-2001055320, Université Côte d'Azur, CNRS, UMR 7275, Institut de Pharmacologie Moléculaire et Cellulaire, Sophia Antipolis, Ingénierie des protéines (IP), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS), Department of Molecular Medicine and Bioprocesses, Institut of Biotechnology, National Autonomous University of Mexico, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Canepari, Marco, Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM)-Instituto de Biotecnología, Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), and Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM)
Subjects: Isopropyl Thiogalactoside, Male, MESH: Oxidation-Reduction, Patch-Clamp Techniques, [SDV]Life Sciences [q-bio], MESH: Genes, Synthetic, Peptide, radio-labeling, Biochemistry, Sodium Channels, law.invention, MESH: Circular Dichroism, MESH: Dose-Response Relationship, Drug, MESH: Recombinant Proteins, Mice, MESH: Histidine, MESH: Scorpion Venoms, law, protein folding, Genes, Synthetic, MESH: Animals, Disulfides, Cloning, Molecular, recombinant, toxin, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, Inclusion Bodies, 0303 health sciences, Expression vector, MESH: Escherichia coli, Circular Dichroism, MESH: Molecular Weight, 030302 biochemistry & molecular biology, Proteolytic enzymes, Centruroides suffusus suffusus, Recombinant Proteins, Recombinant DNA, Protein folding, Oxidation-Reduction, Injections, Intraperitoneal, MESH: Injections, Intraperitoneal, MESH: Isopropyl Thiogalactoside, Plasmids, MESH: Protein Folding, Neurotoxins, Biophysics, Scorpion Venoms, Mice, Inbred Strains, In Vitro Techniques, Transfection, MESH: Mice, Inbred Strains, Cell Line, MESH: Sodium Channels, Lethal Dose 50, 03 medical and health sciences, scorpion, Affinity chromatography, MESH: Plasmids, expression, MESH: Patch-Clamp Techniques, Escherichia coli, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Humans, Histidine, MESH: Cloning, Molecular, MESH: Disulfides, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, MESH: Mice, 030304 developmental biology, MESH: Neurotoxins, MESH: Humans, Molecular mass, Dose-Response Relationship, Drug, MESH: Transfection, electrophysiology, MESH: Inclusion Bodies, MESH: Male, MESH: Cell Line, Molecular Weight, MESH: Lethal Dose 50, chemistry, Heterologous expression
Abstract: International audience; The gene of the four disulfide-bridged Centruroides suffusus suffusus toxin II was cloned into the expression vector pQE30 containing a 6His-tag and a FXa proteolytic cleavage region. This recombinant vector was transfected into Escherichia coli BL21 cells and expressed under induction with isopropyl thiogalactoside (IPTG). The level of expression was 24.6 mg/l of culture medium, and the His tagged recombinant toxin (HisrCssII) was found exclusively in inclusion bodies. After solubilization the HisrCssII peptide was purified by affinity and hydrophobic interaction chromatography. The reverse-phase HPLC profile of the HisrCssII product obtained from the affinity chromatography step showed several peptide fractions having the same molecular mass of 9392.6 Da, indicating that HisrCssII was oxidized forming several distinct disulfide bridge arrangements. The multiple forms of HisrCssII after reduction eluted from the column as a single protein component of 9400.6 Da. Similarly, an in vitro folding of the reduced HisrCssII generated a single oxidized component of HisrCssII, which was cleaved by the proteolytic enzyme FXa to the recombinant CssII (rCssII). The molecular mass of rCssII was 7538.6 Da as expected. Since native CssII (nCssII) is amidated at the C-terminal residue whereas the rCssII is heterologously expressed in the format of free carboxyl end, there is a difference of 1 Da, when comparing both peptides (native versus heterologously expressed). Nevertheless, they show similar toxicity when injected intracranially into mice, and both nCssII and rCssII show the typical electrophysiological properties of beta-toxins in Na(v)1.6 channels, which is for the first time demonstrated here. Binding and displacement experiments conducted with radiolabelled CssII confirms the electrophysiological results. Several problems associated with the heterologously expressed toxins containing four disulfide bridges are discussed.
Published: 2007

14. Calcium channel blocker prevents T helper type 2 cell-mediated airway inflammation

Author: Bruno Gomes, Catherine Leclerc, Pierre Paulet, Bernard Mariamé, Marilena Djata Cabral, Jean-Charles Guéry, Alexandra Gallard, Marc Moreau, Philippe Druet, Magali Savignac, Lucette Pelletier, 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 de biologie du développement (CBD), Centre de Biologie Intégrative (CBI), 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-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre de Biologie Intégrative (CBI)
Subjects: MESH: Inflammation, CD4-Positive T-Lymphocytes, Intracellular Fluid, MESH: Asthma, medicine.medical_treatment, MESH: Calcium Channel Blockers, Critical Care and Intensive Care Medicine, Lymphocyte Activation, Severity of Illness Index, Mice, 0302 clinical medicine, MESH: Animals, MESH: Administration, Intranasal, Lung, 0303 health sciences, Mice, Inbred BALB C, biology, MESH: Dendritic Cells, MESH: Intracellular Fluid, MESH: Enzyme-Linked Immunosorbent Assay, MESH: CD4-Positive T-Lymphocytes, respiratory system, Calcium Channel Blockers, 3. Good health, medicine.anatomical_structure, Cytokine, MESH: Calcium, Female, medicine.symptom, Bronchoalveolar Lavage Fluid, MESH: Injections, Intraperitoneal, Injections, Intraperitoneal, medicine.drug, Pulmonary and Respiratory Medicine, MESH: Mice, Transgenic, Ovalbumin, Nicardipine, MESH: Mice, Inbred BALB C, Inflammation, Enzyme-Linked Immunosorbent Assay, Mice, Transgenic, MESH: Nicardipine, 03 medical and health sciences, Th2 Cells, MESH: Th2 Cells, Intensive care, MESH: Severity of Illness Index, MESH: Cell Proliferation, medicine, Animals, MESH: Lung, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Lymphocyte Activation, MESH: Mice, B cell, Interleukin 4, Administration, Intranasal, 030304 developmental biology, Cell Proliferation, MESH: Ovalbumin, business.industry, MESH: Bronchoalveolar Lavage Fluid, T lymphocyte, Dendritic Cells, Asthma, respiratory tract diseases, Disease Models, Animal, Immunology, biology.protein, Calcium, MESH: Disease Models, Animal, business, MESH: Female, 030215 immunology
Abstract: RATIONALE: Ca(2+) signaling controls the production of T helper (Th) type 2 cytokines known to be deleterious in asthma. Recently, we showed that Ca(2+) signaling was dihydropyridine (DHP)-sensitive in Th2 lymphocytes and that the DHP derivate, nicardipine, used in the treatment of cardiovascular pathologies, prevents Th2-dependent B cell polyclonal activation. OBJECTIVES: We tested the effect of nicardipine in experimental allergic asthma. METHODS: BALB/c mice immunized with ovalbumin (OVA) in alum and challenged with intranasal OVA were treated with nicardipine once the Th2 response, or even airway inflammation, was induced. We also tested the effect of nicardipine in asthma induced by transferring OVA-specific Th2 cells in BALB/c mice exposed to intranasal OVA. We checked the impact of nicardipine on T-cell responses and airway inflammation. MEASUREMENTS AND MAIN RESULTS: Nicardipine inhibited in vitro Ca(2+) response in Th2 cells. In vivo, it impeded the development of Th2-mediated airway inflammation and reduced the capacity of lymphocytes from lung-draining lymph nodes to secrete Th2, but not Th1, cytokines. Nicardipine did not affect antigen presentation to CD4(+) T lymphocytes, nor the initial localization of Th2 cells into the lungs of mice exposed to intranasal OVA; however, it reduced the production of type 2 cytokines and the amplification of the Th2 response in mice with asthma. Conversely, nicardipine had no effect on Th1-mediated airway inflammation. CONCLUSIONS: Nicardipine improves experimental asthma by impairing Th2-dependent inflammation. This study could provide a rationale for developing drugs selectively targeting DHP receptors of Th2 lymphocytes, potentially beneficial in the treatment of asthma.
Published: 2007

15. Synthesis and antimalarial activity of new 1,12-bis(N,N'-acetamidinyl)dodecane derivatives

Author: Michèle Calas, Sharon Wein, Yen Vo Hoang, Roger Escale, Mahama Ouattara, Henri Vial, Université Montpellier 1 (UM1), Laboratoire de Chimie Thérapeutique et Synthèse de Médicaments (LCTSM), Université d'Abidjan-Cocody, Dynamique des interactions membranaires normales et pathologiques (DIMNP), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre d'études sur la cooperation juridique internationale (CECOJI), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Laboratoire des Amino-acides Peptides et Protéines (LAPP), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1)
Subjects: MESH: Plasmodium cynomolgi, Clinical Biochemistry, Amidines, Pharmaceutical Science, Administration, Oral, 01 natural sciences, Biochemistry, Chemical synthesis, chemistry.chemical_compound, Mice, Oral administration, Drug Discovery, MESH: Animals, Antimalarial Agent, Malaria, Falciparum, MESH: Plasmodium falciparum, 0303 health sciences, MESH: Malaria, Falciparum, MESH: Indicators and Reagents, Biological activity, Prodrug, 3. Good health, MESH: Administration, Oral, Molecular Medicine, Female, Injections, Intraperitoneal, MESH: Injections, Intraperitoneal, Plasmodium cynomolgi, Stereochemistry, Dodecane, Plasmodium falciparum, MESH: Malaria, MESH: Hydroxylation, Hydroxylation, 03 medical and health sciences, Antimalarials, MESH: Amidines, In vivo, Alkanes, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, MESH: Mice, 030304 developmental biology, MESH: Humans, 010405 organic chemistry, Organic Chemistry, MESH: Antimalarials, In vitro, 0104 chemical sciences, Malaria, MESH: Alkanes, chemistry, Indicators and Reagents, MESH: Female
Abstract: Amidoxime and O-substituted derivatives of the bis-alkylamidine 1,12-bis(N,N'-acetamidinyl)dodecane were synthesized and evaluated as in vitro and in vivo antimalarial prodrugs. The bis-O-methylsulfonylamidoxime 8 and the bis-oxadiazolone 9 derivatives show relatively potent antimalarial activity after oral administration.
Published: 2007

16. Poly(I)-Poly(C12U) but Not Ribavirin Prevents Death in a Hamster Model of Nipah Virus Infection

Author: Caroline Faure, Philippe Loth, Vincent Deubel, Hugues Contamin, Marie-Claude Georges-Courbot, Pieter Leyssen, Johan Neyts, Sylvain Baize, Biologie des Infections Virales Émergentes - Biology of Emerging Viral Infections (UBIVE), Institut Pasteur [Paris], Laboratoire P4 - Jean Mérieux, Centre Européen de Virologie/Immunologie-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut fédératif de recherche 128-Biosciences [Lyon], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), and Institut Pasteur [Paris] (IP)
Subjects: Male, viruses, MESH: Mesocricetus, MESH: Cricetinae, Median lethal dose, chemistry.chemical_compound, MESH: Chlorocebus aethiops, Cricetinae, MESH: Reverse Transcriptase Polymerase Chain Reaction, Chlorocebus aethiops, Pharmacology (medical), MESH: Animals, MESH: Nipah Virus, MESH: Immunoglobulin G, 0303 health sciences, Interferon inducer, Reverse Transcriptase Polymerase Chain Reaction, virus diseases, MESH: Enzyme-Linked Immunosorbent Assay, Viral Load, 3. Good health, Infectious Diseases, MESH: Cell Survival, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Viral Load, Viral load, Injections, Intraperitoneal, Encephalitis, MESH: Injections, Intraperitoneal, Cell Survival, Hamster, MESH: Vero Cells, Enzyme-Linked Immunosorbent Assay, Biology, Antiviral Agents, MESH: Poly I-C, Lethal Dose 50, 03 medical and health sciences, MESH: Ribavirin, Ribavirin, medicine, Animals, Humans, Vero Cells, 030304 developmental biology, Pharmacology, MESH: Humans, Mesocricetus, 030306 microbiology, Lethal dose, Nipah Virus, biochemical phenomena, metabolism, and nutrition, medicine.disease, biology.organism_classification, Virology, MESH: Male, Disease Models, Animal, Poly I-C, MESH: Lethal Dose 50, chemistry, Immunoglobulin G, MESH: HeLa Cells, MESH: Disease Models, Animal, HeLa Cells
Abstract: Clinical nonrandomized trials demonstrate some efficacy for ribavirin in the treatment of patients with severe Nipah virus-induced encephalitis. We report here that EICAR, the 5-ethynyl analogue of ribavirin, and the OMP-decarboxylase inhibitors 6-aza-uridine and pyrazofurin have strong antiviral activity against Nipah virus replication in vitro. Ribavirin and 6-aza-uridine were tested further in hamsters infected with a lethal dose of Nipah virus. The activity of these small-molecule inhibitors was compared with that of the interferon inducer poly(I)-poly(C 12 U). Both ribavirin and 6-aza-uridine were able to delay but not prevent Nipah virus-induced mortality. Poly(I)-poly(C 12 U), at 3 mg/kg of body weight daily from the day of infection to 10 days postinfection, prevented mortality in 5 of 6 infected animals.
Published: 2006

17. The rat Toxo1 locus directs toxoplasmosis outcome and controls parasite proliferation and spreading by macrophage-dependent mechanisms

Author: Véronique Sergent, Thomas Faraut, Dominique Lagrange, Magali Mas, Marie-Hélène Bessières, Maryline Calise, Marie-France Cesbron-Delauw, Gilbert J. Fournié, Olivier Papapietro, Bernard Pipy, Abdelhadi Saoudi, Céline Colacios, Jean-François Subra, Cordelia Bisanz, Philippe Druet, Pierre Cavaillès, Sylvie Appolinaire, Laboratoire de Génétique Cellulaire (LGC), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, and ProdInra, Migration
Subjects: Male, Genetic Linkage, [SDV]Life Sciences [q-bio], MESH: Genetic Markers, Animals, Congenic, Rats, Inbred BN, TOXOPLASMOSIS, MESH: Animals, ComputingMilieux_MISCELLANEOUS, Subclinical infection, 0303 health sciences, Multidisciplinary, MESH: Toxoplasmosis, Animal, biology, MESH: Toxoplasma, MESH: Genetic Predisposition to Disease, Chromosome Mapping, MESH: Animals, Congenic, Biological Sciences, 3. Good health, [SDV] Life Sciences [q-bio], MESH: Rats, Inbred BN, Female, MESH: Rats, Inbred Lew, Toxoplasma, MESH: Macrophages, Peritoneal, Injections, Intraperitoneal, MESH: Injections, Intraperitoneal, Genetic Markers, MESH: Rats, Congenic, Locus (genetics), RATS, 03 medical and health sciences, MESH: Cell Proliferation, medicine, Animals, Genetic Predisposition to Disease, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Cell Proliferation, 030306 microbiology, TOXO1, Toxoplasma gondii, Fibroblasts, medicine.disease, biology.organism_classification, Toxoplasmosis, Forward genetics, MESH: Male, Chronic infection, Toxoplasmosis, Animal, Genetic marker, Rats, Inbred Lew, MESH: Fibroblasts, Immunology, Macrophages, Peritoneal, RAT, MESH: Microsatellite Repeats, MESH: Chromosome Mapping, MESH: Female, MESH: Linkage (Genetics), Microsatellite Repeats
Abstract: Toxoplasmosis is a healthcare problem in pregnant women and immunocompromised patients. Like humans, rats usually develop a subclinical chronic infection. LEW rats exhibit total resistance toToxoplasma gondiiinfection, which is expressed in a dominant mode. A genome-wide search carried out in a cohort of F2progeny of susceptible BN and resistant LEW rats led to identify on chromosome 10 a major locus of control, which we calledToxo1. Using reciprocal BN and LEW lines congenic for chromosome 10 genomic regions from the other strain,Toxo1was found to govern the issue ofT. gondiiinfection whatever the remaining genome. Analyzes of rats characterized by genomic recombination withinToxo1, reduced the interval down to a 1.7-cM region syntenic to human 17p13.In vitrostudies showed that theToxo1-mediated refractoriness toT. gondiiinfection is associated with the ability of the macrophage to impede the proliferation of the parasite within the parasitophorous vacuole. In contrast, proliferation was observed in fibroblasts whatever the genomic origin ofToxo1. Furthermore,ex vivostudies indicate that macrophage controls parasitic infection spreading by aToxo1-mediated mechanism. This forward genetics approach should ultimately unravel a major pathway of innate resistance to toxoplasmosis and possibly to other apicomplexan parasitic diseases.
Published: 2006

18. Pharmacological properties of a new antimalarial bisthiazolium salt, T3, and a corresponding prodrug, TE3

Author: Sharon Wein, Delphine Margout, Henri Vial, Françoise Bressolle, Nicolas Taudon, Michèle Calas, Olivier Nicolas, Laboratoire de Chimie des Biomolécules et de l'Environnement (LCBE), Université de Perpignan Via Domitia (UPVD)-Université Montpellier 1 (UM1), Dynamique moléculaire des interactions membranaires (DMIM), Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des Amino-acides Peptides et Protéines (LAPP), and Centre National de la Recherche Scientifique (CNRS)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1)
Subjects: Plasmodium, MESH: Rats, Sprague-Dawley, Pharmacology, MESH: Research Support, Non-U.S. Gov't, Rats, Sprague-Dawley, Mice, Oral administration, Pharmacology (medical), Prodrugs, MESH: Animals, ED50, MESH: Plasmodium falciparum, Volume of distribution, 0303 health sciences, Chemistry, Prodrug, 3. Good health, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Infectious Diseases, Injections, Intravenous, Female, Injections, Intraperitoneal, MESH: Injections, Intraperitoneal, MESH: Rats, MESH: Bayes Theorem, Plasmodium falciparum, MESH: Malaria, MESH: Thiazoles, Models, Biological, 03 medical and health sciences, Antimalarials, Pharmacokinetics, In vivo, Animals, Experimental Therapeutics, MESH: Mice, 030304 developmental biology, 030306 microbiology, MESH: Plasmodium, MESH: Models, Biological, Bayes Theorem, MESH: Antimalarials, MESH: Injections, Intravenous, Bioavailability, Malaria, Rats, Thiazoles, Membrane biogenesis, MESH: Prodrugs, MESH: Female
Abstract: A new approach to malarial chemotherapy based on quaternary ammonium that targets membrane biogenesis during intraerythrocytic Plasmodium falciparum development has recently been developed. To increase the bioavailability, nonionic chemically modified prodrugs were synthesized. In this paper, the pharmacological properties of a bisthiazolium salt (T3) and its bioprecursor (TE3) were studied. Their antimalarial activities were determined in vitro against the growth of P. falciparum and in vivo against the growth of P. vinckei in mice. Pharmacokinetic evaluations were performed after T3 (1.3 and 3 mg/kg of body weight administered intravenously; 6.4 mg/kg administered intraperitoneally) and TE3 (1.5 and 3 mg/kg administered intravenously; 12 mg/kg administered orally) administrations to rats. After intraperitoneal administration, very low doses offer protection in a murine model of malaria (50% efficient dose [ED 50 ] of 0.2 to 0.25 mg/kg). After oral administration, the ED 50 values were 13 and 5 mg/kg for T3 and TE3, respectively. Both compounds exerted antimalarial activity in the low nanomolar range. After TE3 administration, rapid prodrug-drug conversion occurred; the mean values of the pharmacokinetic parameters for T3 were as follows: total clearance, 1 liter/h/kg; steady-state volume of distribution, 14.8 liters/kg; and elimination half-life, 12 h. After intravenous administration, T3 plasma concentrations increased in proportion to the dose. The absolute bioavailability was 72% after intraperitoneal administration (T3); it was 15% after oral administration (TE3). T3 plasma concentrations (8 nM) 24 h following oral administration of TE3 were higher than the 50% inhibitory concentrations for the most chloroquine-resistant strains of P. falciparum (6.3 nM).
Published: 2005

19. Effect of nor-trimebutine on neuronal activation induced by a noxious stimulus or an acute colonic inflammation in the rat

Author: Bruno Bonaz, Patrick Mouchet, Valérie Sinniger, Sinniger, Valérie, Groupe d'Etude du Stress et des Interactions Neuro-Digestives (GESIND), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Département d'hépato-gastroentérologie, CHU Grenoble-Université Grenoble Alpes (UGA), This work was supported by Pfizer France, and Université Grenoble Alpes (UGA)-CHU Grenoble
Subjects: Male, Abdominal pain, colitis, MESH: Muscle Contraction, MESH: Neurons, MESH: Rats, Sprague-Dawley, Pharmacology, medicine.disease_cause, Rats, Sprague-Dawley, MESH: Spinal Cord, 0302 clinical medicine, MESH: Colitis, MESH: Animals, General Pharmacology, Toxicology and Pharmaceutics, Anesthetics, Local, visceral afferents, Irritable bowel syndrome, Acetic Acid, Neurons, 0303 health sciences, Local anesthetic, MESH: Proto-Oncogene Proteins c-fos, General Medicine, Immunohistochemistry, trimebutine, MESH: Trimebutine, 3. Good health, MESH: Trinitrobenzenesulfonic Acid, Spinal Cord, Anesthesia, MESH: Acetic Acid, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, Irritation, Proto-Oncogene Proteins c-fos, Injections, Intraperitoneal, MESH: Injections, Intraperitoneal, medicine.drug, Muscle Contraction, c-fos, MESH: Rats, medicine.drug_class, Injections, Subcutaneous, Inflammation, MESH: Anesthetics, Local, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, medicine, Noxious stimulus, Animals, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Colitis, 030304 developmental biology, business.industry, MESH: Injections, Subcutaneous, Trimebutine, MESH: Immunohistochemistry, medicine.disease, somato-visceral pain, MESH: Male, Abdominal Pain, Rats, MESH: Abdominal Pain, Trinitrobenzenesulfonic Acid, MESH: Visceral Afferents, business, 030217 neurology & neurosurgery
Abstract: International audience; Nor-trimebutine is the main metabolite of trimebutine that is used in the treatment of patients with irritable bowel syndrome. Nor-trimebutine has a blocking activity on sodium channels and a potent local anesthetic effect. These properties were used to investigate the effect of nor-trimebutine on spinal neuronal activation induced by models of noxious somato-visceral stimulus and acute colonic inflammation. Nor-trimebutine was administered in rats either subcutaneously 30 min before intraperitoneal administration of acetic acid or intracolonically 30 min before intracolonic infusion of trinitrobenzenesulfonic acid. Abdominal contractions were counted for 1 h as a marker of abdominal pain. c-fos expression was used as a marker of neuronal activation and revealed by immunohistochemistry 1h after intraperitoneal acetic acid injection and 2 h after colonic inflammation. Nor-trimebutine decreased Fos expression in the thoraco-lumbar (peritoneal irritation) and lumbo-sacral (colonic inflammation) spinal cord in laminae I, IIo V, VII and X. This effect was also observed in the sacral parasympathetic nucleus after colonic inflammation. Nor-trimebutine induced a significant decrease of abdominal contractions following intraperitoneal acetic acid injection. These data may explain the effectiveness of trimebutine in the therapy of abdominal pain in the irritable bowel syndrome.
Published: 2005

20. Low ethanol sensitivity and increased ethanol consumption in mice lacking adenosine A2A receptors

Author: Martine Daoust, Catherine Ledent, Mickaël Naassila, Naassila, Mickael, Groupe de Recherche sur l'alcool et les pharmacodépendances - UMR INSERM_S 1247 (GRAP), Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), and Université libre de Bruxelles (ULB)
Subjects: Male, Sucrose, MESH: Body Temperature, MESH: Triazines, Drug Resistance, Adenosine A2A receptor, Administration, Oral, Hypothermia, Choice Behavior, MESH: Mice, Knockout, Body Temperature, MESH: Dose-Response Relationship, Drug, chemistry.chemical_compound, Mice, 0302 clinical medicine, MESH: Hypothermia, MESH: Behavior, Animal, MESH: Animals, Receptor, Mice, Knockout, 0303 health sciences, Quinine, Behavior, Animal, Triazines, General Neuroscience, Drug Tolerance, 3. Good health, Biochemistry, Adenosine a, MESH: Administration, Oral, MESH: Drug Resistance, MESH: Receptor, Adenosine A2A, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, Injections, Intraperitoneal, MESH: Injections, Intraperitoneal, medicine.drug, medicine.medical_specialty, MESH: Ethanol, Alcohol Drinking, Receptor, Adenosine A2A, MESH: Quinine, MESH: Reflex, MESH: Drug Tolerance, MESH: Choice Behavior, 03 medical and health sciences, Sex Factors, MESH: Sex Factors, MESH: Purinergic P1 Receptor Antagonists, Internal medicine, Reflex, medicine, Animals, MESH: Receptors, Purinergic P1, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], ARTICLE, MESH: Mice, 030304 developmental biology, Ethanol, Dose-Response Relationship, Drug, MESH: Sucrose, Antagonist, Receptors, Purinergic P1, Triazoles, MESH: Male, Endocrinology, chemistry, Purinergic P1 Receptor Antagonists, MESH: Triazoles, MESH: Female, 030217 neurology & neurosurgery, MESH: Alcohol Drinking
Abstract: We have shown previously that the severity of handling-induced convulsions during ethanol withdrawal was reduced in A(2A)receptor knock-out (A(2A)R(−/−)) mice. In the present report, we further characterize the role of adenosine A(2A) receptors in ethanol consumption and neurobiological responses to this drug of abuse. Male A(2A)R(−/−) mice showed increased consumption of solutions containing 6 and 20% (v/v) ethanol compared with wild-type (A(2A)R(+/+)) control mice; female A(2A)R(−/−) mice showed increased consumption of solutions containing 6 and 10% ethanol. This slightly higher ethanol consumption was also related to increased ethanol preference. In contrast, A(2A)R(−/−) mice showed normal consumption of solutions containing either sucrose or quinine. Relative to A(2A)R(+/+) mice, A(2A)R(−/−) mice were found to be less sensitive to the sedative effect of 3.0 gm/kg ethanol, as measured by more rapid recovery from ethanol-induced loss of righting reflex, and to the hypothermic effects of 1.5, 3.0, and 4.0 gm/kg ethanol, although plasma ethanol levels did not differ significantly between the two genotypes. The selective adenosine A(2A) receptor antagonist ZM 241385 (4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol) (10–30 mg/kg) significantly attenuated ethanol-induced (4.0 gm/kg) hypothermia in CD1 mice. To assess whether ethanol administration would induce differential tolerance in A(2A)R(−/−) and wild-type mice, we administered ethanol (3.0 gm/kg) over 4 consecutive days and found no difference in the development of tolerance; however, female A(2A)R(−/−) mice showed a lower tolerance-acquisition rate. These data suggest that activating the A(2A) receptors may play a role in suppressing alcohol-drinking behavior and is associated with the sensitivity to the intoxicating effects of acute ethanol administration.
Published: 2002

21. Adenovirus-mediated overexpression of sterol regulatory element binding protein-1c mimics insulin effects on hepatic gene expression and glucose homeostasis in diabetic mice

Author: Isabelle Hainault, Dalila Azzout-Marniche, Pascal Ferré, Lydia Bertry-Coussot, Dominique Bécard, Fabienne Foufelle, Physiologie de la Nutrition et du Comportement Alimentaire ( PNCA ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Physiologie de la Nutrition et du Comportement Alimentaire (PNCA), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Azzout-Marniche, Dalila, AgroParisTech-Institut National de la Recherche Agronomique (INRA), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE)
Subjects: Male, MESH : RNA, Messenger, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], MESH: CCAAT-Enhancer-Binding Proteins, MESH: Recombinant Proteins, Mice, 0302 clinical medicine, Homeostasis, Insulin, Glucose homeostasis, MESH: Animals, 0303 health sciences, MESH: Mice, Inbred CBA, Glycogen, Gene Transfer Techniques, MESH: Adenoviridae, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], MESH: Transcription Factors, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH : Genetic Vectors, 3. Good health, MESH : DNA-Binding Proteins, MESH : Diabetes Mellitus, Experimental, Sterol Regulatory Element Binding Protein 1, medicine.medical_specialty, MESH: Gene Expression, MESH: Gene Transfer Techniques, MESH: Insulin, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Adenoviridae, MESH: Sterol Regulatory Element Binding Protein 1, 03 medical and health sciences, MESH : Sterol Regulatory Element Binding Protein 1, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], RNA, Messenger, MESH : Gene Transfer Techniques, MESH : Injections, Intraperitoneal, MESH : Glucose, Glucokinase, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease, MESH : Gene Expression, Glucose, Endocrinology, [SDV.BBM.MN] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], chemistry, CCAAT-Enhancer-Binding Proteins, Mice, Inbred CBA, MESH: Liver, Transcription Factors, MESH : Transcription Factors, MESH : Insulin, MESH : Mice, Inbred CBA, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, Gene Expression, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, chemistry.chemical_compound, MESH: Genetic Vectors, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], MESH: Diabetes Mellitus, Experimental, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [ SDV.MHEP.PHY ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Recombinant Proteins, MESH: Glucose, DNA-Binding Proteins, Liver, MESH : CCAAT-Enhancer-Binding Proteins, MESH: Homeostasis, MESH : Homeostasis, Phosphoenolpyruvate carboxykinase, MESH: Injections, Intraperitoneal, Injections, Intraperitoneal, MESH : Recombinant Proteins, MESH : Male, Genetic Vectors, 030209 endocrinology & metabolism, Biology, Diabetes Mellitus, Experimental, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [ SDV.BBM.MN ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], Diabetes mellitus, Internal medicine, MESH : Mice, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Internal Medicine, medicine, Animals, MESH : Adenoviridae, MESH: Mice, Transcription factor, MESH: RNA, Messenger, 030304 developmental biology, [ SDV.BC.BC ] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], MESH : Liver, Metabolism, MESH: Male, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, MESH : Animals, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, MESH: DNA-Binding Proteins
Abstract: International audience; In vitro, the transcription factor sterol regulatory element binding protein-1c (SREBP-1c) mimics the positive effects of insulin on hepatic genes involved in glucose utilization, such as glucokinase (GK) and enzymes of the lipogenic pathway, suggesting that it is a key factor in the control of hepatic glucose metabolism. Decreased glucose utilization and increased glucose production by the liver play an important role in the development of the hyperglycemia in diabetic states. We thus reasoned that if SREBP-1c is indeed a mediator of hepatic insulin action, a hepatic targeted overexpression of SREBP-1c should greatly improve glucose homeostasis in diabetic mice. This was achieved by injecting streptozotocin-induced diabetic mice with a recombinant adenovirus containing the cDNA of the mature, transcriptionally active form of SREBP-1c. We show here that overexpressing SREBP-1c specifically in the liver of diabetic mice induces GK and lipogenic enzyme gene expression and represses the expression of phosphoenolpyruvate carboxykinase, a key enzyme of the gluconeogenic pathway. This in turn increases glycogen and triglyceride hepatic content and leads to a marked decrease in hyperglycemia in diabetic mice. We conclude that SREBP-1c has a major role in vivo in the long-term control of glucose homeostasis by insulin.
Published: 2001

22. Effect of some variables on the in vivo determination of scorpion and viper venom toxicities

Author: Naziha Marrakchi, Krifi Mn, Mohamed El Ayeb, K. Dellagi, Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Laboratoire de Purification des Sérums Thérapeutiques, Institut Pasteur de Tunis, Faculté de Médecine de Tunis, Université de Tunis El Manar (UTM), and Laboratoire d'Immunologie, Institut Pasteur de Tunis
Subjects: Male, [SDV]Life Sciences [q-bio], Antivenom, Venom, Pharmacology, Chemical Fractionation, Applied Microbiology and Biotechnology, Mice, MESH: Scorpion Venoms/administration & dosage, MESH: Animals, MESH: Scorpion Venoms/toxicity, 0303 health sciences, MESH: Viper Venoms/toxicity, Mice, Inbred BALB C, biology, 030302 biochemistry & molecular biology, General Medicine, MESH: Neurotoxins/administration & dosage, 3. Good health, Snake venom, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Female, Seasons, MESH: Injections, Intraperitoneal, Injections, Intraperitoneal, Biotechnology, VIPeR, Androctonus australis, Injections, Subcutaneous, MESH: Neurotoxins/toxicity, Neurotoxins, Scorpion, MESH: Mice, Inbred BALB C, Scorpion Venoms, Bioengineering, Viper Venoms, complex mixtures, Lethal Dose 50, 03 medical and health sciences, MESH: Chemical Fractionation, MESH: Mice, Inbred C57BL, biology.animal, Animals, MESH: Mice, 030304 developmental biology, General Immunology and Microbiology, Body Weight, MESH: Injections, Subcutaneous, biology.organism_classification, MESH: Male, MESH: Body Weight, Mice, Inbred C57BL, MESH: Viper Venoms/administration & dosage, MESH: Lethal Dose 50, Immunology, Buthus occitanus, MESH: Female, MESH: Seasons
Abstract: An adequate assessment of scorpion and snake venom LD50 is an important step for accurate evaluation of antivenom sera potencies and the optimization of serotherapy. The LD50 variation of Tunisian scorpion (Androctonus australis garzonii: Aag and Buthus occitanus tunetanus: Bot) venoms with body weight, sex and strain (Swiss or C57Bl/6) of mice used, the route of venom injection, the venom-milking procedures (manually or electrically) and the venom batches have been studied over a 7-year period (1990-1996). Aag venom is 3-4 times more toxic than Bot venom. However for both venoms, the LD50 determined in C57Bl/6 mice, in small body weight animal or by intraperitoneal route were respectively significantly lower than those determined in Swiss mice, in high body weight or by subcutaneous route. Significant LD50 variations (25-50%) were also seen from one electrically prepared batch to another. A good correlation (r = 0·982) was observed between the concentrations of the crude venom toxic fraction determined by ELISA and LD50 values when assessed in vivo. The LD50 variation of Tunisian viper (Cerastes cerastes :C c andVipera lebetina: Vl) venoms with the strain (Swiss or BALB/c), sex and body weight of mice used, the season and the year of venom milking were also investigated over a 3-year period (1990-1992). No significant LD50 variations were observed with the mouse strain, the sex or the season of venom milking. However, LD50 varies significantly with the year of the venom collection and the body weight of mice used. Furthermore, SDS-PAGE analysis shows annual variation for Vl venom composition where no such variations were observed for Cc venom. These results stress the need either for the standardization of the venom LD50 evaluation or of the venom quality used for the development of an efficient antivenom. = 1998 The International Association of Biological Standardization
Published: 1999

23. Induction and duration of long-term potentiation in the hippocampus of the freely moving mouse

Author: Sabrina Davis, Serge Laroche, Timothy V. P. Bliss, Gérard Dutrieux, M.L. Errington, Neurobiologie de l'apprentissage, de la mémoire et de la communication (NAMC), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), and Division of Neurophysiology, National Institute for Medical Research, Mill Hill
Subjects: Movement, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Long-Term Potentiation, MESH: Piperazines, Hippocampus, MESH: Movement, Pharmacology, Receptors, N-Methyl-D-Aspartate, Piperazines, 03 medical and health sciences, Mice, 0302 clinical medicine, MESH: Long-Term Potentiation, MESH: Mice, Inbred C57BL, Animals, MESH: Animals, MESH: Mice, 030304 developmental biology, 0303 health sciences, MESH: Receptors, N-Methyl-D-Aspartate, MESH: Mice, Inbred DBA, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Chemistry, General Neuroscience, Dentate gyrus, musculoskeletal, neural, and ocular physiology, Glutamate receptor, MESH: Electric Stimulation, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Long-term potentiation, Population spike, MESH: Excitatory Amino Acid Antagonists, Electric Stimulation, Mice, Inbred C57BL, nervous system, Mice, Inbred DBA, Dentate Gyrus, Excitatory postsynaptic potential, NMDA receptor, Tetanic stimulation, Neuroscience, Excitatory Amino Acid Antagonists, 030217 neurology & neurosurgery, Injections, Intraperitoneal, MESH: Injections, Intraperitoneal, MESH: Dentate Gyrus
Abstract: International audience; We describe a simple method, using readily available minaturised components, for inducing and monitoring long-term potentiation (LTP) at perforant path-granule cell synapses in the dentate gyrus of the freely moving mouse. Tetanic stimulation induced LTP of the field EPSP and the population spike which persisted for more than 24 h but was not present 10 days after the tetanus. The potentiation of the population spike was proportionately greater than the potentiation of the EPSP (E-S potentiation). Induction of LTP was blocked by intraperitoneal injections of the N-methyl-D-aspartate (NMDA) receptor antagonist, 3-((RS)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP).
Published: 1997

24. The alpha 2-adrenergic antagonist idazoxan enhances the frequency selectivity and increases the threshold of auditory cortex neurons

Author: Jean-Marc Edeline, Neurobiologie de l'apprentissage, de la mémoire et de la communication (NAMC), and Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MESH: Neurons, Dioxanes, Norepinephrine, 0302 clinical medicine, Idazoxan, MESH: Animals, Neurons, 0303 health sciences, education.field_of_study, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Chemistry, General Neuroscience, Imidazoles, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Adrenergic alpha-2 Receptor Antagonists, MESH: Idazoxan, MESH: Evoked Potentials, Auditory, Injections, Intravenous, Excitatory postsynaptic potential, Autoreceptor, Evoked Potentials, Auditory, MESH: Imidazoles, MESH: Injections, Intraperitoneal, Injections, Intraperitoneal, medicine.drug, MESH: Auditory Threshold, medicine.medical_specialty, MESH: Rats, Population, MESH: Acoustic Stimulation, Auditory cortex, 03 medical and health sciences, Internal medicine, MESH: Norepinephrine, medicine, Animals, Rats, Wistar, education, Adrenergic alpha-Antagonists, 030304 developmental biology, MESH: Dioxanes, Auditory Cortex, Antagonist, Auditory Threshold, MESH: Adrenergic alpha-2 Receptor Antagonists, MESH: Rats, Wistar, MESH: Injections, Intravenous, Rats, Electrophysiology, Endocrinology, Acoustic Stimulation, Receptive field, MESH: Adrenergic alpha-Antagonists, MESH: Auditory Cortex, 030217 neurology & neurosurgery
Abstract: International audience; Idazoxan (IDA), an alpha 2 antagonist of adrenoceptors, has been shown to increase cortical release of norepinephrine (NE) by an action mediated primarily by the alpha 2 autoreceptors located on the NE terminals. In the present experiment, IDA application was used to increase the cortial concentration of NE. Single unit activity (n = 107) was recorded in the rat auditory cortex, and the neurons' frequency receptive fields (FRF) were determined before and after systemic (intraperitoneal or intravenous) or local application of IDA. In the whole population (n = 107) there was a decrease in spontaneous activity and/or evoked activity for 84% of the recordings (90/107 cells). Decreased tone-evoked responses were obtained after systemic injections (n = 39), as well as after local applications (n = 68) of IDA. These effects were not observed after either systemic injections (n = 13) or local applications (n = 9) of saline. The signal-to-noise ratio (the mean evoked responses divided by the spontaneous activity) was slightly decreased after systemic injections and slightly increased after local applications. However, after both systemic and local injections the frequency selectivity of the neuronal responses was increased. For a group of neurons (n = 27), testing the FRF at three intensities indicated that this increased selectivity can be expressed at high or middle range intensity but not at low intensity. For 37 cells, the intensity function was tested at the best frequency before and after IDA application, and the threshold for excitatory responses was determined in 28 cases. An increased threshold was observed in 16 of 28 cases after IDA application. Thus, using a pharmacological procedure to increase the extracellular concentration of NE, the dominant inhibitory effect on the auditory cortex neurons led to an enhancement of the frequency selectivity, but also an increase in the threshold of these neurons.
Published: 1995

25. Antihypertensive Drug Guanabenz Is Active In Vivo against both Yeast and Mammalian Prions

Author: Stéphane Bach, Déborah Tribouillard-Tanvier, Nathalie Desban, Hervé Galons, Marc Blondel, Vincent Béringue, Hubert Laude, Cécile Voisset, Didier Vilette, Fabienne Gug, Unité de virologie et immunologie moléculaires, Institut National de la Recherche Agronomique (INRA), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Molécules et cibles thérapeutiques (MCT), Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Station biologique de Roscoff [Roscoff] (SBR), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: PrPSc Proteins, MESH: Protein Structure, Quaternary, MESH: Spleen, Scrapie, Pharmacology, Prion Diseases, Mice, 0302 clinical medicine, Adrenergic alpha-2 Receptor Agonists, MESH: Animals, Receptor, 0303 health sciences, Guanabenz, Multidisciplinary, MESH: PrPSc Proteins, MESH: Saccharomyces cerevisiae, 3. Good health, Survival Rate, Neurological Disorders/Prion Diseases, Tacrine, MESH: Guanabenz, Medicine, Biochemistry/Drug Discovery, medicine.symptom, Injections, Intraperitoneal, MESH: Injections, Intraperitoneal, Research Article, medicine.drug, Genetically modified mouse, Agonist, MESH: Survival Rate, Prions, MESH: Mice, Transgenic, medicine.drug_class, Science, MESH: Sheep, Mice, Transgenic, Saccharomyces cerevisiae, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, 03 medical and health sciences, MESH: Prions, In vivo, medicine, Animals, Protein Structure, Quaternary, MESH: Mice, Antihypertensive Agents, 030304 developmental biology, MESH: Antihypertensive Agents, Sheep, MESH: Prion Diseases, Disease Models, Animal, Mechanism of action, MESH: Receptors, Adrenergic, alpha-2, MESH: Disease Models, Animal, Spleen, 030217 neurology & neurosurgery, Pharmacology/Drug Development, MESH: Tacrine
Abstract: International audience; BACKGROUND: Prion-based diseases are incurable transmissible neurodegenerative disorders affecting animals and humans. METHODOLOGY/PRINCIPAL FINDINGS: Here we report the discovery of the in vivo antiprion activity of Guanabenz (GA), an agonist of alpha2-adrenergic receptors routinely used in human medicine as an antihypertensive drug. We isolated GA in a screen for drugs active in vivo against two different yeast prions using a previously described yeast-based two steps assay. GA was then shown to promote ovine PrP(Sc) clearance in a cell-based assay. These effects are very specific as evidenced by the lack of activity of some GA analogues that we generated. GA antiprion activity does not involve its agonist activity on alpha2-adrenergic receptors as other chemically close anti-hypertensive agents possessing related mechanism of action were found inactive against prions. Finally, GA showed activity in a transgenic mouse-based in vivo assay for ovine prion propagation, prolonging slightly but significantly the survival of treated animals. CONCLUSION/SIGNIFICANCE: GA thus adds to the short list of compounds active in vivo in animal models for the treatment of prion-based diseases. Because it has been administrated for many years to treat hypertension on a daily basis, without major side-effects, our results suggest that it could be evaluated in human as a potential treatment for prion-based diseases.
Published: 2008

26. Optical imaging of luminescence for in vivo quantification of gene electrotransfer in mouse muscle and knee

Author: Capucine Trollet, Daniel Scherman, Michel Bureau, Elodie Pradines, Johanne Seguin, C. Bloquel, Unité de Pharmacologie Chimique et Génétique (UPCG - UMR_S 640/UMR 8151), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-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)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), This work was in part supported by a grant I.PA (Imagerie du Petit Animal, CNRS-CEA), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC), Centre National de la Recherche Scientifique (CNRS) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Paris Descartes - Paris 5 (UPD5) - Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM) - Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP) - Centre National de la Recherche Scientifique (CNRS) - Institut de Recherche pour le Développement (IRD) - Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP) - Centre National de la Recherche Scientifique (CNRS) - Institut de Recherche pour le Développement (IRD) - Université Paris Descartes - Paris 5 (UPD5), and Autard, Delphine
Subjects: [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Knee Joint, Gene Expression, Gene electrotransfer, Firefly Luciferin, chemistry.chemical_compound, Mice, 0302 clinical medicine, Genes, Reporter, Luciferases, Firefly, Image Processing, Computer-Assisted, MESH: Animals, [INFO.INFO-BT]Computer Science [cs]/Biotechnology, MESH: Firefly Luciferin, 0303 health sciences, Microscopy, MESH: Knee Joint, MESH: Kinetics, Electroporation, MESH: Comparative Study, MESH: Image Processing, Computer-Assisted, Luciferin, MESH: Lumines, 030220 oncology & carcinogenesis, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Female, MESH: Injections, Intraperitoneal, Injections, Intraperitoneal, Biotechnology, Research Article, MESH: Gene Expression, lcsh:Biotechnology, Firefly luciferin, Biology, Transfection, Injections, 03 medical and health sciences, In vivo, lcsh:TP248.13-248.65, MESH: Injections, Animals, MESH: Electroporation, Luciferase, MESH: Luminescent Agents, Muscle, Skeletal, 030304 developmental biology, [SDV.IB] Life Sciences [q-bio]/Bioengineering, MESH: Luciferases, Firefly, Luminescent Agents, MESH: Genes, Reporter, Reproducibility of Results, Molecular biology, In vitro, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, Mice, Inbred C57BL, Kinetics, [INFO.INFO-BT] Computer Science [cs]/Biotechnology, chemistry, Luminescent Measurements, Biophysics, Luminescence, MESH: Female
Abstract: Background Optical imaging is an attractive non-invasive way to evaluate the expression of a transferred DNA, mainly thanks to its lower cost and ease of realization. In this study optical imaging was evaluated for monitoring and quantification of the mouse knee joint and tibial cranial muscle electrotransfer of a luciferase encoding plasmid. Optical imaging was applied to study the kinetics of luciferase expression in both tissues. Results The substrate of luciferase (luciferin) was injected either intraperitonealy (i.p.) or in situ into the muscle or the knee joint. Luminescence resulting from the luciferase-luciferin reaction was measured in vivo with a cooled CCD camera and/or in vitro on tissue lysate. Maximal luminescence of the knee joint and muscle after i.p. (2.5 mg) or local injection of luciferin (50 μg in the knee joint, 100 μg in the muscle) were highly correlated. With the local injection procedure adopted, in vivo and in vitro luminescences measured on the same muscles significantly correlated. Luminescence measurements were reproducible and the signal level was proportional to the amount of plasmid injected. In vivo luciferase activity in the electrotransfered knee joint was detected for two weeks. Intramuscular electrotransfer of 0.3 or 3 μg of plasmid led to stable luciferase expression for 62 days, whereas injecting 30 μg of plasmid resulted in a drop of luminescence three weeks after electrotransfer. These decreases were partially associated with the development of an immune response. Conclusion A particular advantage of the i.p. injection of substrate is a widespread distribution at luciferase production sites. We have also highlighted advantages of local injection as a more sensitive detection method with reduced substrate consumption. Besides, this route of injection is relatively free of uncontrolled parameters, such as diffusion to the target organ, crossing of biological barriers and evidencing variations in local enzymatic kinetics, probably related to the reaction medium in the targeted organ. Optical imaging was shown to be a sensitive and relevant technique to quantify variations of luciferase activity in vivo. Further evaluation of the effective amount of luciferase in a given tissue by in vivo optical imaging relies on conditions of the enzymatic reaction and light absorption and presently requires in vitro calibration for each targeted organ.
Published: 2006

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26 results on '"MESH: Injections, Intraperitoneal"'

1. The tyrosine kinase inhibitor imatinib mesylate suppresses uric acid crystal-induced acute gouty arthritis in mice

2. Erythropoietin Restores C-Fiber Function and Prevents Pressure Ulcer Formation in Diabetic Mice

3. Population Pharmacokinetics and Dosing Recommendations for Cisplatin during Intraperitoneal Peroperative Administration

4. Toxic Effects of Iterative Intraperitoneal Administration of Zinc Gluconate in Rats

5. Benefit of tianeptine and morphine in a transgenic model of familial amyotrophic lateral sclerosis

6. Intraperitoneal clearance as a potential biomarker of cisplatin after intraperitoneal perioperative chemotherapy: a population pharmacokinetic study

7. Experimental Meningococcal Sepsis in Congenic Transgenic Mice Expressing Human Transferrin

8. Acute food deprivation reduces expression of diazepam-binding inhibitor, the precursor of the anorexigenic octadecaneuropeptide ODN, in mouse glial cells

9. Intraoperative chemotherapy with cisplatin and epinephrine after cytoreductive surgery in patients with recurrent ovarian cancer: a phase I study

10. Overexpressed or intraperitoneally injected human transferrin prevents photoreceptor degeneration in rd10 mice

11. Intra-operative intra-peritoneal chemotherapy with cisplatin in patients with peritoneal carcinomatosis of ovarian cancer

12. Cocaine-induced reinstatement in rats: evidence for a critical role of cocaine stimulus properties

13. Four disulfide-bridged scorpion beta neurotoxin CssII: heterologous expression and proper folding in vitro

14. Calcium channel blocker prevents T helper type 2 cell-mediated airway inflammation

15. Synthesis and antimalarial activity of new 1,12-bis(N,N'-acetamidinyl)dodecane derivatives

16. Poly(I)-Poly(C12U) but Not Ribavirin Prevents Death in a Hamster Model of Nipah Virus Infection

17. The rat Toxo1 locus directs toxoplasmosis outcome and controls parasite proliferation and spreading by macrophage-dependent mechanisms

18. Pharmacological properties of a new antimalarial bisthiazolium salt, T3, and a corresponding prodrug, TE3

19. Effect of nor-trimebutine on neuronal activation induced by a noxious stimulus or an acute colonic inflammation in the rat

20. Low ethanol sensitivity and increased ethanol consumption in mice lacking adenosine A2A receptors

21. Adenovirus-mediated overexpression of sterol regulatory element binding protein-1c mimics insulin effects on hepatic gene expression and glucose homeostasis in diabetic mice

22. Effect of some variables on the in vivo determination of scorpion and viper venom toxicities

23. Induction and duration of long-term potentiation in the hippocampus of the freely moving mouse

24. The alpha 2-adrenergic antagonist idazoxan enhances the frequency selectivity and increases the threshold of auditory cortex neurons

25. Antihypertensive Drug Guanabenz Is Active In Vivo against both Yeast and Mammalian Prions

26. Optical imaging of luminescence for in vivo quantification of gene electrotransfer in mouse muscle and knee

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26 results on '"MESH: Injections, Intraperitoneal"'

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