Testing for Organophosphate‐Induced Delayed Polyneuropathy

Moretto, Angelo

doi:10.1002/0471140856.tx1105s00

Cited by 5 publications

(5 citation statements)

References 26 publications

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“…Importantly, it has been suggested that interactions of OPs with such noncholinesterase targets may contribute to the more delayed and persistent effects observed after chronic exposure to OPs (Lotti and Moretto, 2005;Costa, 2006).…”

Section: Discussionmentioning

confidence: 99%

Diisopropylfluorophosphate Impairs the Transport of Membrane-Bound Organelles in Rat Cortical Axons

Gao

Naughton

Wulff

et al. 2015

Journal of Pharmacology and Experimental Therapeutics

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The extensive use of organophosphates (OPs) is an ongoing environmental health concern due to multiple reports of OPrelated neurologic abnormalities. The mechanism of the acute toxicity of OPs has been attributed to inhibition of acetylcholinesterase (AChE), but there is growing evidence that this may not account for all the long-term neurotoxic effects of OPs. In previous experiments (using ex vivo and in vitro model systems) we observed that the insecticide OP chlorpyrifos impaired the movements of vesicles and mitochondria in axons. Here, using a time-lapse imaging technique, we evaluated the OP-nerve agent diisopropylfluorophosphate (DFP) across a wide range of concentrations (subnanomolar to micromolar) for effects on fast axonal transport of membrane-bound organelles (MBOs) that contain the amyloid precursor protein (APP) tagged with the fluorescent marker Dendra2 (APPDendra2). Both 1 and 24 hours of exposure to DFP and a positive control compound, colchicine, resulted in a decrease in the velocity of anterograde and retrograde movements of MBOs and an increase in the number of stationary MBOs. These effects occurred at picomolar (100 pM) to low nanomolar (0.1 nM) concentrations that were not associated with compromised cell viability or cytoskeletal damage. Moreover, the effects of DFP on axonal transport occurred at concentrations that did not inhibit AChE activity, and they were not blocked by cholinergic receptor antagonists. Given the fundamental importance of axonal transport to neuronal function, these observations may explain some of the long-term neurologic deficits that have been observed in humans who have been exposed to OPs.

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Section: Discussionmentioning

confidence: 99%

Diisopropylfluorophosphate Impairs the Transport of Membrane-Bound Organelles in Rat Cortical Axons

Gao

Naughton

Wulff

et al. 2015

Journal of Pharmacology and Experimental Therapeutics

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“…[29][30][31][32][33]). Two widely used current models that contain a statistical description of fission are the code GEMINI++ [34] in which fission is described by the transition-state approach of Moretto [35] and the code SMM ( [36], and references therein) in which low-energy fission is described by an empirical parametrization and higher-energy fission is treated as one of the possible channels of statistical multifragmentation.…”

Section: Introductionmentioning

confidence: 99%

Microscopic dynamical description of proton-induced fission with the constrained molecular dynamics model

et al. 2015

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The microscopic description of nuclear fission still remains a topic of intense basic research. Understanding nuclear fission, apart from a theoretical point of view, is of practical importance for energy production and the transmutation of nuclear waste. In nuclear astrophysics, fission sets the upper limit to the nucleosynthesis of heavy elements via the r-process. In this work we initiated a systematic study of intermediate energy proton-induced fission using the Constrained Molecular Dynamics (CoMD) code. The CoMD code implements an effective interaction with a nuclear matter compressibility of K=200 (soft EOS) with several forms of the density dependence of the nucleon-nucleon symmetry potential. Moreover, a constraint is imposed in the phase-space occupation for each nucleon restoring the Pauli principle at each time step of the collision. A proper choice of the surface parameter of the effective interaction has been made to describe fission. In this work, we present results of fission calculations for proton-induced reactions on : a) 232 Th at 27 and 63 MeV, b) 235 U at 10, 30, 60 and 100 MeV, and c) 238 U at 100 and 660 MeV. The calculated observables include fission-fragment mass distributions, total fission energies, neutron multiplicities and fission times. These observables are compared to available experimental data. We show that the microscopic CoMD code is able to describe the complicated many-body dynamics of the fission process at intermediate and high energy and give a reasonable estimate of the fission time scale. Sensitivity of the results to the density dependence of the nucleon symmetry potential (and, thus, the nuclear symmetry energy) is found. Further improvements of the code are necessary to achieve a satisfactory description of low energy fission in which shell effects play a dominant role.Understanding the mechanism of nuclear fission, that is the transformation of a single heavy nucleus into two receeding fragments, has been a long journey of fruitful research and debate and, still today, is far from being complete. Upon its discovery, fission was interpreted by Meitner and Frisch [22] as the division of a charged liquid drop due to the interplay of the repulsive Coulomb force between the protons and the surface tension due to the attractive nucleon-nucleon interaction. In the seminal paper of Bohr and Wheeler [23], fission was described with a liquid-drop model and the first estimates of fission probalilities were obtained based on statistical arguments. The first detailed calculations of potential energies of deformed nuclear drops were performed by Frankel and Metropolis in 1947 [24] employing the ENIAC, one of the first digital computers. Despite the success in the interpretation of fission based on the liquid-drop model, the prevailing asymmetry in the mass distribution of the minor actinides could not be deciphered until shell corrections to the macroscopic liquid drop were taken into account (see below). A detailed statistical model that could describe asymmetric fission was...

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“…Wang et al showed that miR-155 is down-regulated in peripheral blood mononuclear cells (PBMCs) from GBS patients and that silencing miR-155 profoundly promotes the production of Th1-type cytokines in vitro 13. Interestingly, delayed onset distal polyneuropathy is a consequence of severe intoxication due to the inhibition of the neuropathy target esterase (NTE) enzyme,14 also known as patatin-like phospholipase domain-containing 6 (PNPLA6), in nervous tissues by certain organophosphorous compounds. Interestingly, we found that the PNPLA6 gene was targeted by miR-214 and miR-454 from the TargetScan database, and both miRNAs were up-regulated in our study.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA expression profiling in human acute organophosphorus poisoning and functional analysis of dysregulated miRNAs

Yuan¹,

Yuan²,

Tang³

et al. 2018

Afr H. Sci.

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ObjectiveAcute organophosphorus(OP) pesticide poisoning is associated with dysfunctions in multiple organs, especially skeletal muscles, the nervous system and the heart. However, little is known about the specific microRNA (miRNA) changes that control the pathophysiological processes of acute OP poisoning damage. We aimed to explore miRNA expression profiles and gain insight into molecular mechanisms of OP toxic effects.MethodsMicroRNA expression was analyzed by TaqMan Human MicroRNA Array analysis and subsequent validated with quantitive PCR. The targets of the significantly different miRNAs were predicted with miRNA prediction databases, and pathway analysis of the predicted target genes was performed using bioinformatics resources.Results37 miRNAs were significantly different in the sera of poisoned patients compared to the healthy controls, including 29 miRNAs that were up-regulated and 8 miRNAs that were down-regulated. Functional analysis indicated that many pathways potentially regulated by these miRNAs are involved in skeletal muscle, nervous system and heart disorders.ConclusionThis study mapped changes in the serum miRNA expression profiles of poisoning patients and predicted functional links between miRNAs and their target genes in the regulation of acute OP poisoning. Our findings are an important resource for further understanding the role of these miRNAs in the regulation of OP-induced injury.

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Testing for Organophosphate‐Induced Delayed Polyneuropathy

Cited by 5 publications

References 26 publications

Diisopropylfluorophosphate Impairs the Transport of Membrane-Bound Organelles in Rat Cortical Axons

Diisopropylfluorophosphate Impairs the Transport of Membrane-Bound Organelles in Rat Cortical Axons

Microscopic dynamical description of proton-induced fission with the constrained molecular dynamics model

MicroRNA expression profiling in human acute organophosphorus poisoning and functional analysis of dysregulated miRNAs

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