Description
Non-clinical drug safety evaluation, the assessment of the safety profile of therapeutic agents through the conduct of laboratory studies in in vitro systems and in animals, is an essential step in the progress of new pharmaceuticals heading toward the ultimate goal of clinical trials and, eventually, approval. In Drug Safety Evaluation: Methods and Protocols, expert researchers detail a compendium of analytical technologies with a focus on clarity and applicability in real life laboratory practice. These meticulous contributions feature key topics such as acute to chronic general toxicity studies, histopathology studies, reproductive toxicity studies, genotoxicity studies, safety pharmacology studies, investigative toxicity studies, and safety biomarker studies. As a volume in the highly successful Methods in Molecular Biology(TM) series, chapters include brief introductions to their respective subjects, lists of the necessary materials, step-by-step, readily reproducible protocols, and tips on troubleshooting and avoiding known pitfalls. Comprehensive and authoritative, Drug Safety Evaluation: Methods and Protocols serves as an ideal guide to this field, helpful to pharmaceutical scientists, toxicologists, biochemists, and molecular biologists as well as scientists from all other disciplines who wish to translate these thorough methods into their own work. Part I: General Toxicology 1. Developing Combination Drugs in Preclinical Studies Alberto Lodola 2. Preclinical Evaluation of Juvenile Toxicity Paul C. Barrow, Stphane Barbellion, and Jeanne Stadler Part II: Pathology 3. Necropsy and Sampling Procedures in Rodents Laurence Fiette and Mohamed Slaoui 4. Histopathology Procedures: From Tissue Sampling to Histopathological Evaluation Mohamed Slaoui and Laurence Fiette 5. Principles and Methods of Immunohistochemistry Jos A. Ramos-Vara 6. Tissue Microarrays and Digital Image Analysis Denise Ryan, Laoighse Mulrane, Elton Rexhepaj, and William M. Gallagher Part III: Genetic Toxicology 7. Micronucleus Assay and Labeling of Centromeres with FISH Technique Ilse Decordier, Raluca Mateuca, and Micheline Kirsch-Volders 8. The Use of Bacterial Repair Endonucleases in the Comet Assay Andrew R. Collins Part IV: Safety Pharmacology 9. Manual Whole-Cell Patch-Clamping of the HERG Cardiac K+ Channel Xiao-Liang Chen, Jiesheng Kang, and David Rampe Part V: Generation and Analysis of Transcriptomics Data 10. Generation and Analysis of Transcriptomics Data Philip D. Glaves and Jonathan D. Tugwood 11. Protocols of Two-Dimensional Difference Gel Electrophoresis (2D-DIGE) to Investigate Mechanisms of Toxicity Emmanuelle Com, Albrecht Gruhler, Martine Courcol, and Jean-Charles Gautier 12. Protocols and Applications of Cellular Metabolomics in Safety Studies Using Precision-Cut Tissue Slices and Carbon 13 NMR Gabriel Baverel, Sophie Renault, Hassan Faiz, Maha El Hage, Catherine Gauthier, Agns Duplany, Bernard Ferrier, and Guy Martin 13. Statistical Analysis of Quantitative RT-PCR Results Richard Khan-Malek and Ying Wang 14. Evaluation of Mitochondrial Respiration in Cultured Rat Hepatocytes Jean-Pierre Marchandeau and Gilles Labbe Part VI : Screening Assays for Developmental Toxicity 15. FETAX Assay for Evaluation of Developmental Toxicity Isabelle Mouche, Laure Malesic, and Olivier Gillardeaux 16. Evaluation of Embryotoxicity Using the Zebrafish Model Lisa Truong, Stacey L. Harper, and Robert L. Tanguay Part VII: Chemical Protein Adducts 17. Protocols of In vitro Protein Covalent Binding Studies in Liver Jean-Franois Lvesque, Stephen H. Day, and Allen N. Jones 18. Utilization of MALDI-TOF to Determine Chemical-Protein Adduct Formation In vitro Ashley A. Fisher, Matthew T. Labenski, Terrence J. Monks, and Serrine S. Lau 19. Utilization of LC-MS/MS Analyses to Identify Site-Specific Chemical Protein Adducts In vitro Ashley A. Fisher, Matthew T. Labenski, Terrence J. Monks, and Serrine S. Lau 20. 1-Dimensional Western Blotting Coupled to LC-MS/MS Analysis to Identify Chemical-Adducted Proteins in Rat Urine Matthew T. Labenski, Ashley A. Fisher, Terrence J. Monks, and Serrine S. Lau 21. Identification of Chemical Adducted Proteins in Urine by Multi-Dimensional Protein Identification Technology (LC/LC-MS/MS) Matthew T. Labenski, Ashley A. Fisher, Terrence J. Monks, and Serrine S. Lau Part VIII: Safety Biomarkers 22. Optimization of SELDI for Biomarker Detection in Plasma Jean-Francois Lonard, Martine Courcol, and Jean-Charles Gautier 23. Differential Proteomics Incorporating iTRAQ Labelling and Multi-Dimensional Separations Ben C. Collins, Thomas Y.K. Lau, Stephen R. Pennington, and William M. Gallagher 24. NMR and MS Methods for Metabonomics Frank Dieterle, Bjrn Riefke, Gtz Schlotterbeck, Alfred Ross, Hans Senn, and Alexander Amberg 25. Absolute Quantification of Toxicological Biomarkers by Multiple Reaction Monitoring Thomas Y.K. Lau, Ben C. Collins, Peter Stone, Ning Tang, William M. Gallagher, and Stephen R. Pennington
