English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Tools annual

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Presents the access of premium content as premium feature

Premium Content

Global: Zendy Plus annual

Global: Zendy Free Plan

Background  One of the leading causes of death and illness within the agriculture industry is through unintentionally ingesting or inhaling organophosphate pesticides. OP intoxication directly inhibits acetylcholinesterase, resulting in an excitatory signaling cascade leading to fasciculation, loss of control of bodily fluids, and seizures.    Methods  Our model was developed using a discrete, rules-based modeling approach in NetLogo. This model includes acetylcholinesterase, the nicotinic acetylcholine receptor responsible for signal transduction, a single release of acetylcholine, organophosphate inhibitors, and a theoretical novel medical countermeasure. We have parameterized the system considering the molecular reaction rate constants in an agent-based approach, as opposed to apparent macroscopic rates used in differential equation models.    Results  Our model demonstrates how the cholinergic crisis can be mitigated by therapeutic intervention with an acetylcholinesterase activator. Our model predicts signal rise rates and half-lives consistent with  in vitro  and  in vivo  data in the absence and presence of inhibitors. It also predicts the efficacy of theoretical countermeasures acting through three mechanisms: increasing catalytic turnover of acetylcholine, increasing acetylcholine binding affinity to the enzyme, and decreasing binding rates of inhibitors.    Conclusion  We present a model of the neuromuscular junction confirming observed acetylcholine signaling data and suggesting that developing a countermeasure capable of reducing inhibitor binding, and not activator concentration, is the most important parameter for reducing organophosphate (OP) intoxication.    Electronic supplementary material  The online version of this article (doi:10.1186/1742-4682-11-42) contains supplementary material, which is available to authorized users.

Potential new therapeutic modality revealed through agent-based modeling of the neuromuscular junction and acetylcholinesterase inhibition