A protein nanocomposite for ultra-fast, efficient and non-irritating skin decontamination of nerve agents

Nanoscale ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 4400-4409 ◽  
Author(s):  
Jiapeng Wang ◽  
Yao Li ◽  
Jingyi Huang ◽  
Wanhua Li ◽  
Yuan Luo ◽  
...  
Keyword(s):  
Nerve Agents ◽  
Skin Decontamination

The nanocomposite would decontaminate nerve agents within several seconds without irritating the skin, reducing the poisoning degree in vivo.

scholarly journals Skin Decontamination with Mineral Cationic Carrier Against Sarin Determined In Vivo

2009 ◽  
Vol 60 (2) ◽  
pp. 173-177 ◽  
Author(s):  
Ante Vučemilović ◽  
Mirko Hadžija ◽  
Ivan Jukić
Keyword(s):  
Ion Exchange ◽  
Chemical Defense ◽  
Therapeutic Efficacy ◽  
Research Team ◽  
Nerve Agents ◽  
Defense Research ◽  
Bioactive Potential ◽  
Skin Decontamination

Skin Decontamination with Mineral Cationic Carrier Against Sarin DeterminedIn VivoOur Institute's nuclear, biological, and chemical defense research team continuously investigates and develops preparations for skin decontamination against nerve agents. In thisin vivostudy, we evaluated skin decontamination efficacy against sarin by a synthetic preparation called Mineral Cationic Carrier (MCC®) with known ion exchange, absorption efficacy and bioactive potential. Mice were treated with increasing doses of sarin applied on their skin, and MCC® was administered immediately after contamination. The results showed that decontamination with MCC® could achieve therapeutic efficacy corresponding to 3 x LD50of percutaneous sarin and call for further research.

scholarly journals Catalytic activity and stereoselectivity of engineered phosphotriesterases towards structurally different nerve agents in vitro

2021 ◽  
Author(s):  
Anja Köhler ◽  
Benjamin Escher ◽  
Laura Job ◽  
Marianne Koller ◽  
Horst Thiermann ◽  
...  
Keyword(s):  
Plasma Clearance ◽  
Nerve Agents ◽  
Inhibition Assay ◽  
Ache Inhibition ◽  
Catalytic Activities ◽  
Chiral Lc ◽  
Hydrolysis Of ◽  
Medical Countermeasures

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.

scholarly journals Comparative determination of the efficacy of bispyridinium oximes in paraoxon poisoning / Usporedno određivanje učinkovitosti bispiridinijevih oksima pri trovanju paraoksonom

2015 ◽  
Vol 66 (2) ◽  
pp. 129-134 ◽  
Author(s):  
Suzana Žunec ◽  
Božica Radić ◽  
Kamil Kuča ◽  
Kamil Musilek ◽  
Ana Lucić Vrdoljak
Keyword(s):  
Therapeutic Efficacy ◽  
Standard Therapy ◽  
Organophosphorus Compounds ◽  
Nerve Agents ◽  
Therapeutic Efficiency ◽  
Hi 6 ◽  
Comparative Determination

Abstract The inability of standard therapy to provide adequate protection against poisoning by organophosphorus compounds (pesticides and nerve agents) motivated us to search for new, more effective oximes. We investigated the pharmacotoxicological properties of six experimental K-oximes (K027, K033, K048, K074, K075, and K203) in vivo. The therapeutic efficacy of K-oximes (at doses of 5 or 25 % of their LD50) combined with atropine was assessed in paraoxon-poisoned mice and compared with conventionally used oximes HI-6 and TMB-4. The bisoxime K074 was the most toxic (LD50=21.4 mg kg-1) to mice, while monoxime K027 was the least toxic (LD50=672.8 mg kg-1). With the exception of K033, all of the tested K-oximes showed better therapeutic efficiency than HI-6 and TMB-4. K027 and K048 stood out by demonstrating low acute toxicities and ensuring protective indices ranging from 60.0 to 100.0 LD50 of paraoxon. Taking into account that these two oximes showed a similar therapeutic efficacy regardless of the applied doses, our results suggest that K027 and K048 could be antidotes for paraoxon intoxication.

Protein adduct binding properties of tabun-subtype nerve agents after exposure in vitro and in vivo

2020 ◽  
Vol 321 ◽  
pp. 1-11 ◽  
Author(s):  
Feiyan Fu ◽  
Haibo Liu ◽  
Runli Gao ◽  
Pengcheng Zhao ◽  
Xiaogang Lu ◽  
...  
Keyword(s):  
Nerve Agents ◽  
Binding Properties ◽  
Protein Adduct

Some Possibilities to Study New Prophylactics against Nerve Agents

2019 ◽  
Vol 19 (12) ◽  
pp. 970-979 ◽  
Author(s):  
J. Bajgar ◽  
J. Kassa ◽  
T. Kucera ◽  
K. Musilek ◽  
D. Jun ◽  
...  
Keyword(s):  
Cholinesterase Inhibitors ◽  
Chemical Warfare Agents ◽  
Nerve Agents ◽  
Chemical Warfare ◽  
Huperzine A ◽  
Acetylcholinesterase Inhibition ◽  
Effective Prophylaxis ◽  
Warfare Agents

Nerve agents belong to the most dangerous chemical warfare agents and can be/were misused by terrorists. Effective prophylaxis and treatment is necessary to diminish their effect. General principles of prophylaxis are summarized (protection against acetylcholinesterase inhibition, detoxification, treatment “in advance” and use of different drugs). They are based on the knowledge of mechanism of action of nerve agents. Among different examinations, it is necessary to test prophylactic effectivity in vivo and compare the results with protection in vitro. Chemical and biological approaches to the development of new prophylactics would be applied simultaneously during this research. Though the number of possible prophylactics is relatively high, the only four drugs were introduced into military medical practice. At present, pyridostigmine seems to be common prophylactic antidote; prophylactics panpal (tablets with pyridostigmine, trihexyphenidyl and benactyzine), transant (transdermal patch containing HI-6) are other means introduced into different armies as prophylactics. Scavenger commercionally available is Protexia®. Future development will be focused on scavengers, and on other drugs either reversible cholinesterase inhibitors (e.g., huperzine A, gallantamine, physostigmine, acridine derivatives) or other compounds.

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