HomeCoursesMEDSCI 204: Pharmacology and ToxicologyLecture 23 Lecture 23 1. What parameters can only be discovered in animals, not in vitro? Toxicity, pharmacologyWhat parameters can only be discovered in animals, not in vitro?== Toxicity, pharmacology 2. What happened with thalidomide? Taken for pregnancy sickness, wasn't tested in pregnant rodents, caused teratogenic injury to fetusWhat happened with thalidomide?== Taken for pregnancy sickness, wasn't tested in pregnant rodents, caused teratogenic injury to fetus 3. What happened with thalidomide? Taken for pregnancy sickness, wasn't tested in pregnant rodents, caused teratogenic injury to fetusWhat happened with thalidomide?== Taken for pregnancy sickness, wasn't tested in pregnant rodents, caused teratogenic injury to fetus 4. What are the 3 Rs of animal ethics? Replacement (use in vitro if possible), reduction (minimise number of animals), refinement (use technology to minimise animal discomfort)What are the 3 Rs of animal ethics? ==Replacement (use in vitro if possible), reduction (minimise number of animals), refinement (use technology to minimise animal discomfort) 5. What happened with TGN1412? Passed animal testing but developed severe inflammatory reaction in humansWhat happened with TGN1412?== Passed animal testing but developed severe inflammatory reaction in humans 6. How are human diseases recapitulated in animals? Selectively bred, genetic modification, drug/chemical inducement, surgicalHow are human diseases recapitulated in animals? ==Selectively bred, genetic modification, drug/chemical inducement, surgical 7. What are benefits of animal models? Discover MOA, new drug targets, disease pathology, dosing and toxicityWhat are benefits of animal models?== Discover MOA, new drug targets, disease pathology, dosing and toxicity 8. What aspects of disease phenotype/causality should animal models ideally manifest? Face validity (symptoms), construct validity (biology eg. genetics, physiology), predictive validity (responsive to therapy)What aspects of disease phenotype/causality should animal models ideally manifest?== Face validity (symptoms), construct validity (biology eg. genetics, physiology), predictive validity (responsive to therapy) 9. What are limitations of animal models?== Don't fully recapitulate due to physiological differences between animals and humans; efficacy in single animal strain doesn't represent heterogenity in humans, study desighn (time course, subjective responses, group size), clinical response not predictively valid 10. How to overcome animal model limitations? Use different animal modelsHow to overcome animal model limitations?== Use different animal models 11. What are the characteristics of PD? Loss of dopamenergic neurons, lewy body aggregates (alpha synuclein)What are the characteristics of PD?== Loss of dopamenergic neurons, lewy body aggregates (alpha synuclein) 12. What types of animal models recapitulate PD? Neurotoxin (neural loss but no lewy body formation), genetic model (lewy bodies but little neural loss)What types of animal models recapitulate PD?== Neurotoxin (neural loss but no lewy body formation), genetic model (lewy bodies but little neural loss) 13. What is a syngeneic tumour model? Cancer cells from diseased mouse cultured and injected into other mice (immunocompetent)What is a syngeneic tumour model?== Cancer cells from diseased mouse cultured and injected into other mice (immunocompetent) 14. What is cell line xenograft model? Cancer cells from diseased human cultured and injected into immunodeficient mice (to avoid rejection)What is cell line xenograft model?== Cancer cells from diseased human cultured and injected into immunodeficient mice (to avoid rejection) 15. What is a disadvantage of both? Cells undergo selection during cultureWhat is a disadvantage of both? ==Cells undergo selection during culture 16. What are geneticly engineered mouse models? Knock out tumour suppressor genes or knock in oncogenes using genetic engineeringWhat are geneticly engineered mouse models?== Knock out tumour suppressor genes or knock in oncogenes using genetic engineering 17. What is the disadvantage with genetically engineered mouse models? Long time for tumour developmentWhat is the disadvantage with genetically engineered mouse models?== Long time for tumour development 18. What is a patient-derived xenograft model? Tumour surgically removed and engrafted in immunodeficeint mice.What is a patient-derived xenograft model?== Tumour surgically removed and engrafted in immunodeficeint mice. 19. What are advatages of in vivo models? heterogeneity of original (tumour retained)What are advatages of in vivo models?== heterogeneity of original (tumour retained) Loading...
