Early diagnosis of nerve agent exposure with a mobile test kit and implications for medical countermeasures: a trigger to react

2020 ◽  
Vol 166 (2) ◽  
pp. 99-102
Author(s):  
Timo Wille ◽  
Snezana Djordjević ◽  
Franz Worek ◽  
Horst Thiermann ◽  
Slavica Vučinić

Recent uses of nerve agents underline the need of early diagnosis as trigger to react (initiating medical countermeasures, avoiding cross-contamination). As organophosphorus (OP) pesticide poisoning exerts the same pathomechanism, that is, inhibition of the pivotal enzyme acetylcholinesterase (AChE), a portable cholinesterase (ChE) test kit was applied in an emergency room for rapid diagnosis of OP poisoning. OP nerve agents or pesticides result in the inhibition of AChE. As AChE is also expressed on erythrocytes, patient samples are easily available. However, in most clinics only determination of plasma butyrylcholinesterase (BChE) is established which lacks a pathophysiological correlate, shows higher variability in the population and behaves different regarding inhibition by OP and reactivation by oximes. The ChE test kit helped to diagnose atypical cases of OP poisoning, for example, missing of typical muscarinic symptoms, and resulted in administration of pralidoxime, the oxime used in Serbia. The ChE test kit also allows an initial assessment whether an oxime therapy is successful. In one case report, AChE activity increased after oxime administration indicating therapeutic success whereas BChE activity did not. With only BChE at hand, this therapeutic effect would have been missed. As inhibition of AChE or BChE activity is determined, the CE-certified device is a global diagnostic tool for all ChE inhibitors including carbamates which might also be misused as chemical weapon. The ChE test kit is a helpful point-of-care device for the diagnosis of ChE inhibitor poisoning. Its small size and easy menu-driven use advocate procurement where nerve agent and OP pesticide exposure are possible.

2020 ◽  
Vol 44 (4) ◽  
pp. 391-401 ◽  
Author(s):  
Katie M Rubin ◽  
Bruce A Goldberger ◽  
Timothy J Garrett

Abstract A recently proposed model for the incorporation of xenobiotics of forensic interest into the human skeleton suggests nerve agent metabolites may incorporate into bone at relatively elevated concentrations based on their unique chemical properties. To test the hypothesis that nerve agent metabolites interact with bone, methods for the extraction, isolation and semi-quantitative detection of nerve agent metabolites (MPA, EMPA, IMPA, iBuMPA, CMPA and PMPA, corresponding to the nerve agents VX, Russian VX, sarin, cyclosarin and soman, respectively) from osseous tissue were developed using liquid chromatography–mass spectrometry with both quadrupole time-of-flight and triple quadrupole (QqQ) instruments. The optimized methods were validated on the QqQ instrument. Despite high ion suppression, the achieved limits of detection (5–20 pg/g for four analytes; 350 pg/g for the fifth analyte) were lower than many of those published for the same analytes in other biomatrices, including serum and urine. These methods were tested on the skeletal remains of minipigs exposed to the chemical weapon VX in vivo. The VX metabolite was detected in multiple minipig bone samples; to the authors’ knowledge, this is the first time in vivo nerve agent exposure has been detected from bone. Further, detected concentrations and diaphyseal-to-epiphyseal area count ratios reflect animal exposure history. Although the results are limited, they are promising, indicating that nerve agent metabolites may interact with bone as a pharmacokinetic compartment and can be extracted from bone postmortem. Additional studies, assessing the effects of different agents, exposure pathways and taphonomic variables, are needed; however, these results suggest the method may be used with human bone to detect use of chemical weapons from postmortem biomatrices even well after a suspected attack. More general implications for both nerve agent toxicology and skeletal toxicology are also discussed.


2021 ◽  
Vol 10 (12) ◽  
pp. 2627
Author(s):  
Pierre-Edouard Fournier ◽  
Sophie Edouard ◽  
Nathalie Wurtz ◽  
Justine Raclot ◽  
Marion Bechet ◽  
...  

The Méditerranée Infection University Hospital Institute (IHU) is located in a recent building, which includes experts on a wide range of infectious disease. The IHU strategy is to develop innovative tools, including epidemiological monitoring, point-of-care laboratories, and the ability to mass screen the population. In this study, we review the strategy and guidelines proposed by the IHU and its application to the COVID-19 pandemic and summarise the various challenges it raises. Early diagnosis enables contagious patients to be isolated and treatment to be initiated at an early stage to reduce the microbial load and contagiousness. In the context of the COVID-19 pandemic, we had to deal with a shortage of personal protective equipment and reagents and a massive influx of patients. Between 27 January 2020 and 5 January 2021, 434,925 nasopharyngeal samples were tested for the presence of SARS-CoV-2. Of them, 12,055 patients with COVID-19 were followed up in our out-patient clinic, and 1888 patients were hospitalised in the Institute. By constantly adapting our strategy to the ongoing situation, the IHU has succeeded in expanding and upgrading its equipment and improving circuits and flows to better manage infected patients.


Author(s):  
Anja Köhler ◽  
Benjamin Escher ◽  
Laura Job ◽  
Marianne Koller ◽  
Horst Thiermann ◽  
...  

AbstractHighly toxic organophosphorus nerve agents, especially the extremely stable and persistent V-type agents such as VX, still pose a threat to the human population and require effective medical countermeasures. Engineered mutants of the Brevundimonas diminuta phosphotriesterase (BdPTE) exhibit enhanced catalytic activities and have demonstrated detoxification in animal models, however, substrate specificity and fast plasma clearance limit their medical applicability. To allow better assessment of their substrate profiles, we have thoroughly investigated the catalytic efficacies of five BdPTE mutants with 17 different nerve agents using an AChE inhibition assay. In addition, we studied one BdPTE version that was fused with structurally disordered PAS polypeptides to enable delayed plasma clearance and one bispecific BdPTE with broadened substrate spectrum composed of two functionally distinct subunits connected by a PAS linker. Measured kcat/KM values were as high as 6.5 and 1.5 × 108 M−1 min−1 with G- and V-agents, respectively. Furthermore, the stereoselective degradation of VX enantiomers by the PASylated BdPTE-4 and the bispecific BdPTE-7 were investigated by chiral LC–MS/MS, resulting in a several fold faster hydrolysis of the more toxic P(−) VX stereoisomer compared to P(+) VX. In conclusion, the newly developed enzymes BdPTE-4 and BdPTE-7 have shown high catalytic efficacy towards structurally different nerve agents and stereoselectivity towards the toxic P(−) VX enantiomer in vitro and offer promise for use as bioscavengers in vivo.


2018 ◽  
Vol 12 (1) ◽  
pp. 011501 ◽  
Author(s):  
Ting-Yen Wei ◽  
Tzung-Hai Yen ◽  
Chao-Min Cheng

The Analyst ◽  
2022 ◽  
Author(s):  
Guozhen He ◽  
Tao Dong ◽  
Zhaochu Yang ◽  
Are Branstad ◽  
Lan Huang ◽  
...  

Chronic Obstructive pulmonary disease (COPD) has become the third leading causes of global death. Insufficiency in early-diagnosis and treatment of COPD, especially COPD exacerbation, leads to tremendous economic burden and...


RSC Advances ◽  
2019 ◽  
Vol 9 (19) ◽  
pp. 10693-10701 ◽  
Author(s):  
You Kyoung Chung ◽  
Seonggyun Ha ◽  
Tae Gyun Woo ◽  
Young Dok Kim ◽  
Changsik Song ◽  
...  

Binding energies and geometries of 1 : 1 complexes formed between nerve agent simulant DMMP and 13 thiourea derivatives (TUn) were calculated and compared with the sensing efficiencies of TUn from QCM analysis.


2002 ◽  
Vol 9 (2) ◽  
pp. 83-89 ◽  
Author(s):  
SYH Tang ◽  
JTS Chan

The incidence of Tokyo subway attack by the Aum Shinrikyo cult in 1995 had raised the concern of the use of nerve agent as a weapon in terrorist attack. The recent event in World Trade Centre in New York city had further brought our attention to the possibility of terrorist attacks using these agents. In view of the high possibility of nerve agents being used as chemical weapon, medical personnel should have a clear knowledge of these agents. This article aim to provide a detailed discussion of these agents.


2020 ◽  
Vol 75 (10) ◽  
pp. 1111-1124 ◽  
Author(s):  
Jasper Boeddinghaus ◽  
Thomas Nestelberger ◽  
Luca Koechlin ◽  
Desiree Wussler ◽  
Pedro Lopez-Ayala ◽  
...  

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