Pesticides are unique environmental contaminants that are specifically introduced into the environment to control pests, often by killing them. Although pesticide application serves many important purposes, including protection against crop loss and against vector-borne diseases, there are significant concerns over the potential toxic effects of pesticides to non-target organisms, including humans. In many cases, the molecular target of a pesticide is shared by non-target species, leading to the potential for untoward effects. Here, we review the history of pesticide usage and the neurotoxicity of selected classes of pesticides, including insecticides, herbicides, and fungicides, to humans and experimental animals. Specific emphasis is given to linkages between exposure to pesticides and risk of neurological disease and dysfunction in humans coupled with mechanistic findings in humans and animal models. Finally, we discuss emerging techniques and strategies to improve translation from animal models to humans.

Neurotoxicity of pesticides.

: We propose to perform a phase I/II study comparing two nutraceuticals and placebo that target mediators identified in our prior dynamic modeling study of Gulf War Illness (GWI). We will repeat the dynamic modeling before treatment and on therapy to assess our modeling and the impact of the interventions on the homeostatic networks we have identified, with an added focus on the glutathione/redox system. In our prior study Dynamic Modeling in GWI we used an exercise stress model (rest, peak VO2, and 7 follow-up sampling points) to measure the mediators of relapse in the context of their interactive homeostatic networks. We surveyed theresponse of genes and blood-borne biomarkers in order to interrogate and map regulation of neuro-endocrine-autonomic-immune function in these subjects as compared to GW era sedentary healthy controls. We applied an integrative systems-based approach rooted in computational biology connecting gene expression and biomarkers to pathways and to symptoms in order to identify potential therapeutic targets as well as optimal strategies for manipulation of these targets. Using this data we have developed a virtual model of the illness, which we have used to identify potential therapeutic targets. The proposed project is directed at the validation of pharmacologic mediation of illness targets for GWI, identified using an integrative systems-based approach to the study of molecular and cellular markers.

https://apps.dtic.mil/sti/pdfs/AD1090654.pdf

Testing the Model: A Phase 1/11 Randomized Double Blind Placebo Control Trial of Targeted Therapeutics: Liposomal Glutathione and Curcumin

Neurotoxicity in acute and repeated organophosphate exposure.

Mitochondrial dysfunction as a trigger of innate immune responses and inflammation.

A treatise on Organophosphate pesticide pollution: Current strategies and advancements in their environmental degradation and elimination.

https://stacks.cdc.gov/view/cdc/37629/cdc_37629_DS1.pdf

Recent research on Gulf War illness and other health problems in veterans of the 1991 Gulf War: Effects of toxicant exposures during deployment

Publisher Summary This chapter deals with sampling for microbial forensic investigations. An ability to determine the source, type, and extent of a biological attack reliably and accurately is critical not only to the public health response but also for successful criminal prosecution of the perpetrator. Environmental samples are one of the key elements of evidence in both epidemiological and forensic investigations. Therefore, it is critical that methods used for sample collection and analyses are validated. In terms of public health, even an unconfirmed positive result from analysis of environmental samples can usefully initiate prophylaxis, treatment, or both, as well as implementation of containment measures. For forensic investigation, a higher level of certainty is needed than that for epidemiological investigation: beyond reasonable doubt becomes the standard that all of the methods, individually and collectively, must meet. Attaining a higher level of certainty has resource implications for conducting forensic investigations, as well as requirements for methods that must meet the standards of legal acceptability. Microbial forensics is an infant science whose development was forced because of the need to tie the 2001 anthrax attack to a specific perpetrator, by tracing the source of the biological material to a particular laboratory. It is likely that additional methods will be developed to improve the ability to pinpoint sources of microbes other than anthrax. Such improved methods will have value not only in forensic investigations, but also by enhancing the capability and robustness of epidemiological investigations.

Jack Melling

Papers

Recent research on Gulf War illness and other health problems in veterans of the 1991 Gulf War: Effects of toxicant exposures during deployment

Sampling for Microbial Forensic Investigations