Phrenic nerve-hemidiaphragm as a highly sensitive replacement assay for determination of functional botulinum toxin antibodies
| Autor: | Peter Rigsby, Yvonne Liu, Dorothea Sesardic, Christine Rasetti-Escargueil, R.G.A. Jones |
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| Přispěvatelé: | National Institute for Biological Standards and Control (NIBSC), Medicines and Healthcare Products Regulatory Agency (MHRA), This work was supported by a Home Office Grant. |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Male
MESH: Toxicology / methods [SDV]Life Sciences [q-bio] Botulinum Antitoxin Pharmacology Toxicology medicine.disease_cause Assays Mice MESH: Phrenic Nerve / drug effects MESH: Animals Immunoassay Mice Inbred BALB C MESH: Diaphragm / drug effects Botulinum toxin MESH: Immunologic Factors / immunology MESH: Botulinum Antitoxin / analysis Phrenic Nerve [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology MESH: Immunologic Factors / classification Botulinum neurotoxin Antitoxin medicine.drug MESH: Botulinum Antitoxin / immunology MESH: Botulinum Antitoxin / classification Diaphragm MESH: Mice Inbred BALB C Biology Sensitivity and Specificity complex mixtures Antibodies MESH: Immunoassay / methods In vivo medicine Animals Immunologic Factors Potency Paralysis MESH: Immunologic Factors / analysis MESH: Mice MESH: Phenytoin / pharmacology Toxin [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology MESH: Male MESH: Sensitivity and Specificity Phrenic nerve-hemidiaphragm Ex vivo Phenytoin Immunology Clostridium botulinum |
| Zdroj: | Toxicon Toxicon, Elsevier, 2011, 57 (7-8), pp.1008-1016. ⟨10.1016/j.toxicon.2011.04.003⟩ |
| ISSN: | 0041-0101 |
| DOI: | 10.1016/j.toxicon.2011.04.003⟩ |
| Popis: | International audience; Botulinum neurotoxins induce a prolonged muscle paralysis by specifically blocking the release of neuronal transmitters from peripheral nerve junctions. Potency testing of toxin and antitoxin therapies is entirely dependent on mouse lethality bioassay which is associated with extreme suffering of large numbers of animals to ensure high precision. The mouse phrenic nerve-diaphragm assay is an ex vivo assay that closely mimics in vivo respiratory paralysis offering substantial refinement and reduction in the number of animals used. A range of botulinum antitoxin standards, one licenced product and experimental antitoxins were tested for neutralising potency using ex vivo hemidiaphragm assay and compared with in vivo determined activities. Overall, there was an excellent agreement between neutralising activity detected by the two assay systems and for each toxin serotype using only 4-7 replicates for each product (almost perfect concordance for type A antitoxins: ρ = 0.997, and substantial concordance for type B antitoxins: ρ = 0.991 and type E antitoxins: ρ = 0.964, respectively). These findings confirm that the mouse nerve-diaphragm preparation can provide a functional ex vivo replacement assay for specific, sensitive and precise assessment of toxin and antitoxin activity. |
| Databáze: | OpenAIRE |
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