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Marion Ehrich – Pesticide Neurotoxicity More or Less Created by Joshua Gray Learning Objectives: Describe the risks and benefits of pesticides and describe the ideal pesticide. Associate mechanisms of acute organophosphate toxicity with present and future prospects for treatment Distinguish non-acute toxicities associated with organophosphate exposure, including means for amelioration and prevention Identify potential benefits to medical research resulting from organophosphate studies. Recommended prerequisite topics Dose response Nerve cell signaling, action potential, and neurotransmitters Acetylcholine and acetylcholine receptor mechanism of action Study questions What class of insecticides are the most likely to cause unintentional neurotoxicity? If an organophosphate is toxic to both humans and insects, what preventive measures can be taken to allow the use of the chemical but reduce human toxicity? Describe how the acetylcholine functions at the neuromuscular junction. Contrast the sympathetic and parasympathetic nervous systems. Which nervous system is overactivated upon organophosphate exposure? Why are organophosphates particularly toxic to the brain? Describe the mechanism by which atropine reverses organophosphate toxicity. What are the problems of oximes for the treatment of organophosphates? Describe how scavengers might be used to treat organophosphate exposure. What are the features of delayed neuropathy that occur in humans and animals following exposure to organophosphates? What are some of the risk factors that lead to increased toxicity? What are two of the drugs used to treat organophosphate-induced delayed neuropathy and what are the negative effects associated with these drugs? What in vitro assay was used by Dr. Ehrich to predict organophosphate-induced delayed neurotoxicity? What are four methods by which risk from organophosphates can be reduced? How might organophosphates inform research on PON2, which has a role in neurological disorders? Application of this Lecture to Vision and Change Core Concepts and Competencies. Core Concepts Evolution Implied suitability of animal models for understanding human health. Structure and Function Discussion of the neuromuscular junction and blood brain barrier, modification with toxicants. Information flow, exchange, and storage Impact of sex differences on response to organophosphate exposure. Pathways and transformations of energy and matter Systems Core Competencies Ability to apply the process of science. Understanding of mechanism of action of toxicants leads to discoveries that impact medicine. Ability to use quantitative reasoning Ability to use modeling and simulation Ability to tap into the Understanding toxicology of organophosphates impacts basic knowledge interdisciplinary about the Blood Brain Barrier that might lead to human health nature of science discoveries. Ability to communicate and collaborate with other disciplines Ability to understand the relationship of science and society Importance of pesticides and their risk/benefit analysis. Vision and Change Core Concepts. Evolution. The diversity of life evolved over time by processes of mutation, selection, and genetic change. Structure and Function. Basic units of structure define the function of all living things. Information flow, exchange, and storage. The growth and behavior of organisms are activated through the expression of genetic information in context. Pathways and transformations of energy and matter. Biological systems grow and change by processes based upon chemical transformation pathways and are governed by the laws of thermodynamics. Systems. Living systems are interconnected and interacting. Core Competencies and Disciplinary Practice. Ability to apply the process of science. Biology is evidence based and grounded in the formal practices of observation, experimentation, and hypothesis testing. Ability to use quantitative reasoning. Biology relies on applications of quantitative analysis and mathematical reasoning. Ability to use modeling and simulation. Biology focuses on the study of complex systems. Ability to tap into the interdisciplinary nature of science. Biology is an interdisciplinary science. Ability to communicate and collaborate with other disciplines. Biology is a collaborative scientific discipline. Ability to understand the relationship of science and society. Biology is conducted in a societal context.