scholarly journals Complex View on Poisoning with Nerve Agents and Organophosphates

2005 ◽  
Vol 48 (1) ◽  
pp. 3-21 ◽  
Author(s):  
Jiří Bajgar
Keyword(s):  
Clinical Status ◽  
Chemical Warfare Agents ◽  
Nerve Agents ◽  
New Drugs ◽  
Molecular Forms ◽  
Therapeutic Drugs ◽  
Sh Group ◽  
Warfare Agents ◽  
Op Nerve Agents ◽  
Living Organisms

OP/nerve agents are still considered as important chemicals acting on living organisms and widely used in human practice. Nerve agents are the most lethal chemical warfare agents. They are characterized according to their action as compounds influencing cholinergic nerve transmission via inhibition of AChE. The symptoms of intoxication comprise nicotinic, muscarinic and central symptoms, for some OP/nerve agents, a delayed neurotoxicity is observed. Cholinesterases (AChE and BuChE) are characterized as the main enzymes involved in the toxic effect of these compounds including their molecular forms. The activity of both enzymes (and molecular forms) is influenced by inhibitors and other factors such as pathological states. There are different methods for cholinesterase determination, however, the most frequent is the method based on the hydrolysis of thiocholine esters and following detection of free SH-group of the released thiocholine. The diagnosis of OP/nerve agents poisoning is based on anamnesis, the clinical status of the intoxicated organism and on cholinesterase determination in the blood. Some principles of prophylaxis against OP/nerve agents poisoning comprising the administration of reversible cholinesterase inhibitors such as pyridostigmine (alone or in combination with other drugs), scavengers such as preparations of cholinesterases, some therapeutic drugs and possible combinations are given. Basic principles of the treatment of nerve agents/OP poisoning are described. New drugs for the treatment are under experimental study based on new approaches to the mechanism of action.

scholarly journals In Vitro Interaction of Organophosphono- and Organophosphorothioates with Human Acetylcholinesterase

Molecules ◽  
2020 ◽  
Vol 25 (13) ◽  
pp. 3029
Author(s):  
Franz Worek ◽  
Horst Thiermann ◽  
Marianne Koller ◽  
Timo Wille
Keyword(s):  
Human Plasma ◽  
Biological Effects ◽  
Chemical Warfare Agents ◽  
Nerve Agents ◽  
Ache Inhibitors ◽  
Potential Structure ◽  
Warfare Agents ◽  
Op Nerve Agents

The implementation of the Chemical Weapons Convention (CWC) in 1997 was a milestone in the prohibition of chemical warfare agents (CWA). Yet, the repeated use of CWA underlines the ongoing threat to the population. Organophosphorus (OP) nerve agents still represent the most toxic CWA subgroup. Defensive research on nerve agents is mainly focused on the “classical five”, namely tabun, sarin, soman, cyclosarin and VX, although Schedule 1 of the CWC covers an unforeseeable number of homologues. Likewise, an uncounted number of OP pesticides have been produced in previous decades. Our aim was to determine the in vitro inhibition kinetics of selected organophosphono- and organophosphorothioates with human AChE, as well as hydrolysis of the agents in human plasma and reactivation of inhibited AChE, in order to derive potential structure–activity relationships. The investigation of the interactions of selected OP compounds belonging to schedule 1 (V-agents) and schedule 2 (amiton) of the CWC with human AChE revealed distinct structural effects of the P-alkyl, P-O-alkyl and N,N-dialkyl residues on the inhibitory potency of the agents. Irrespective of structural modifications, all tested V-agents presented as highly potent AChE inhibitors. The high stability of the tested agents in human plasma will most likely result in long-lasting poisoning in vivo, having relevant consequences for the treatment regimen. In conclusion, the results of this study emphasize the need to investigate the biological effects of nerve agent analogues in order to assess the efficacy of available medical countermeasures.

scholarly journals Nerve agents: emergency preparedness

2020 ◽  
Vol 166 (1) ◽  
pp. 42-46
Author(s):  
Alan George Andrew Weir ◽  
S Makin ◽  
J Breeze
Keyword(s):  
Emergency Preparedness ◽  
Emergency Services ◽  
Chemical Properties ◽  
Chemical Warfare Agents ◽  
Nerve Agents ◽  
Clinical Effects ◽  
Individual Agent ◽  
Warfare Agents ◽  
The Individual ◽  
The Uk

Nerve agents (NAs) are a highly toxic group of chemical warfare agents. NAs are organophosphorus esters with varying physical and chemical properties depending on the individual agent. The most recently developed class of NA is ‘Novichok’, the existence of which was first revealed in the early 1990s, just before Russia signed the Chemical Weapons Convention. In 1984, Iraq became the first nation to deploy NA on the battlefield when they used tabun against Iranian military forces in Majnoon Island near Basra. The first terrorist use of an NA is believed to be the attack in Matsumoto, Japan, on 27 June 1994 by the Aum Shinrikyo doomsday cult. Symptoms and ultimate toxicity from NA poisoning are related to the agent involved, the form and degree of exposure, and rapidity of medical treatment. The classic toxidrome of significant exposure to NA comprises bronchorrhoea, bronchospasm, bradycardia and convulsions, with an onset period of as early as a few seconds depending on the mode and extent of exposure. If medical management is not instituted rapidly, death may occur in minutes by asphyxiation and cardiac arrest. In the UK, emergency preparedness for NA poisoning includes an initial operational response programme across all blue light emergency services and key first responders. This paper describes the development, pathophysiology, clinical effects and current guidance for management of suspected NA poisoning. It also summarises the known events in which NA poisoning has been confirmed.

scholarly journals Detection Papers with Chromogenic Chemosensors for Direct Visual Detection and Distinction of Liquid Chemical Warfare Agents

Chemosensors ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 30 ◽  
Author(s):  
Vladimír Pitschmann ◽  
Lukáš Matějovský ◽  
Kamila Lunerová ◽  
Michal Dymák ◽  
Martin Urban ◽  
...  
Keyword(s):  
Chemical Warfare Agents ◽  
Nerve Agents ◽  
Chemical Warfare ◽  
Bromocresol Green ◽  
Ph Indicator ◽  
Nitrogen Mustards ◽  
Experimental Development ◽  
Influence Of Water ◽  
Warfare Agents ◽  
Hydrophobic Treatment

This work provides a summary of our results in the area of the experimental development of detection paper for the detection of liquid phase chemical warfare agents (drops, aerosol), the presence of which is demonstrated by the development of characteristic coloring visible to the naked eye. The basis of the detection paper is a cellulose carrier saturated with the dithienobenzotropone monomer (RM1a)–chromogenic chemosensor sensitive to nerve agents of the G type, blister agent lewisite, or choking agent diphosgene. We achieve a higher coloring brilliance and the limit certain interferences by using this chemosensor in the mix of the o-phenylendiamine-pyronine (PY-OPD). We prove that the addition of the Bromocresol Green pH indicator even enables detection of nerve agents of the V type, or, nitrogen mustards, while keeping a high stability of the detection paper and its functions for other chemical warfare agents. We resolve the resistance against the undesirable influence of water by providing a hydrophobic treatment of the carrier surface.

scholarly journals Enzymatic Degradation of Organophosphorus Pesticides and Nerve Agents by EC: 3.1.8.2

Catalysts ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1365
Author(s):  
Marek Matula ◽  
Tomas Kucera ◽  
Ondrej Soukup ◽  
Jaroslav Pejchal
Keyword(s):  
Catalytic Activity ◽  
Organophosphorus Compounds ◽  
Organophosphorus Pesticides ◽  
Chemical Warfare Agents ◽  
Enzyme Commission Number ◽  
Nerve Agents ◽  
Organophosphorus Acid Anhydrolase ◽  
Warfare Agents ◽  
Heavy Burden ◽  
Medical Countermeasures

The organophosphorus substances, including pesticides and nerve agents (NAs), represent highly toxic compounds. Standard decontamination procedures place a heavy burden on the environment. Given their continued utilization or existence, considerable efforts are being made to develop environmentally friendly methods of decontamination and medical countermeasures against their intoxication. Enzymes can offer both environmental and medical applications. One of the most promising enzymes cleaving organophosphorus compounds is the enzyme with enzyme commission number (EC): 3.1.8.2, called diisopropyl fluorophosphatase (DFPase) or organophosphorus acid anhydrolase from Loligo Vulgaris or Alteromonas sp. JD6.5, respectively. Structure, mechanisms of action and substrate profiles are described for both enzymes. Wild-type (WT) enzymes have a catalytic activity against organophosphorus compounds, including G-type nerve agents. Their stereochemical preference aims their activity towards less toxic enantiomers of the chiral phosphorus center found in most chemical warfare agents. Site-direct mutagenesis has systematically improved the active site of the enzyme. These efforts have resulted in the improvement of catalytic activity and have led to the identification of variants that are more effective at detoxifying both G-type and V-type nerve agents. Some of these variants have become part of commercially available decontamination mixtures.

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.

Future Considerations for the Medical Management of Nerve-Agent Intoxication

2003 ◽  
Vol 18 (3) ◽  
pp. 208-216 ◽  
Author(s):  
Pål Aas
Keyword(s):  
Chemical Warfare Agents ◽  
Nerve Agents ◽  
Nerve Agent ◽  
Chemical Warfare ◽  
Weapons Of Mass Destruction ◽  
Terrorist Attacks ◽  
International Conflicts ◽  
Mass Destruction ◽  
The World ◽  
Warfare Agents

AbstractThe use of chemical warfare agents against civilians and unprotected troops in international conflicts or by terrorists against civilians is considered to be a real threat, particularly following the terrorist attacks on 11 September 2001 against the World Trade Center in New York and against the Pentagon in Washington, DC. Over the past 10 years, terrorists have been planning to use or have used chemical warfare agents on several occasions around the world, and the attacks in 2001 illustrate their willingness to use any means of warfare to cause death and destruction among civilians. In spite of new international treaties with strong verification measures and with an aim to prohibit and prevent the use of weapons of mass destruction, nevertheless, some countries and terrorist groups have been able to develop, produce, and use such weapons, particularly nerve agents, in domestic terrorist attacks or during warfare in international conflicts. This article reviews current medical therapy for nerve-agent intoxication and discusses possible future improvement of medical therapies.Present medical counter-measures against nerve agents are not sufficiently effective particularly in protecting the brain. Therefore, new and more effective countermeasures must be developed to enable better medical treatment of civilians and military personnel following exposure to nerve agents. Therefore, it is important with an enhanced effort by all countries, to improve and increase research in medical countermeasures, in the development of protective equipment, and in carrying out regular training of medical and emergency personnel as well as of military nuclear, biological, or chemical (NBC) units. Only then will nations be able to reduce the risk from and prevent the use of such weapons of mass destruction (WMD).

scholarly journals Biological Toxins as the Potential Tools for Bioterrorism

2019 ◽  
Vol 20 (5) ◽  
pp. 1181 ◽  
Author(s):  
Edyta Janik ◽  
Michal Ceremuga ◽  
Joanna Saluk-Bijak ◽  
Michal Bijak
Keyword(s):  
Botulinum Toxin ◽  
Clostridium Perfringens ◽  
Review Paper ◽  
Chemical Warfare Agents ◽  
Mechanisms Of Action ◽  
Chemical Warfare ◽  
High Potential ◽  
Low Doses ◽  
Warfare Agents ◽  
Living Organisms

Biological toxins are a heterogeneous group produced by living organisms. One dictionary defines them as “Chemicals produced by living organisms that have toxic properties for another organism”. Toxins are very attractive to terrorists for use in acts of bioterrorism. The first reason is that many biological toxins can be obtained very easily. Simple bacterial culturing systems and extraction equipment dedicated to plant toxins are cheap and easily available, and can even be constructed at home. Many toxins affect the nervous systems of mammals by interfering with the transmission of nerve impulses, which gives them their high potential in bioterrorist attacks. Others are responsible for blockage of main cellular metabolism, causing cellular death. Moreover, most toxins act very quickly and are lethal in low doses (LD50 < 25 mg/kg), which are very often lower than chemical warfare agents. For these reasons we decided to prepare this review paper which main aim is to present the high potential of biological toxins as factors of bioterrorism describing the general characteristics, mechanisms of action and treatment of most potent biological toxins. In this paper we focused on six most danger toxins: botulinum toxin, staphylococcal enterotoxins, Clostridium perfringens toxins, ricin, abrin and T-2 toxin. We hope that this paper will help in understanding the problem of availability and potential of biological toxins.

scholarly journals UiO-66-NH2 and Zeolite-Templated Carbon Composites for the Degradation and Adsorption of Nerve Agents

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3837
Author(s):  
Jaeheon Lee ◽  
Dongwon Ka ◽  
Heesoo Jung ◽  
Kyeongmin Cho ◽  
Youngho Jin ◽  
...  
Keyword(s):  
Gas Adsorption ◽  
Chemical Warfare Agents ◽  
Nerve Agents ◽  
Carbon Composites ◽  
Surface Areas ◽  
Pore Size Distributions ◽  
Warfare Agents ◽  
Metal Organic ◽  
Characterization Studies ◽  
Templated Carbon

Composites of metal-organic frameworks and carbon materials have been suggested to be effective materials for the decomposition of chemical warfare agents. In this study, we synthesized UiO-66-NH2/zeolite-templated carbon (ZTC) composites for the adsorption and decomposition of the nerve agents sarin and soman. UiO-66-NH2/ZTC composites with good dispersion were prepared via a solvothermal method. Characterization studies showed that the composites had higher specific surface areas than pristine UiO-66-NH2, with broad pore size distributions centered at 1–2 nm. Owing to their porous nature, the UiO-66-NH2/ZTC composites could adsorb more water at 80% relative humidity. Among the UiO-66-NH2/ZTC composites, U0.8Z0.2 showed the best degradation performance. Characterization and gas adsorption studies revealed that beta-ZTC in U0.8Z0.2 provided additional adsorption and degradation sites for nerve agents. Among the investigated materials, including the pristine materials, U0.8Z0.2 also exhibited the best protection performance against the nerve agents. These results demonstrate that U0.8Z0.2 has the optimal composition for exploiting the degradation performance of pristine UiO-66-NH2 and the adsorption performance of pristine beta-ZTC.

scholarly journals O5C.5 Sarin exposures in a cohort of british military participants in human experimental research at porton down 1945–1987

2019 ◽  
Vol 76 (Suppl 1) ◽  
pp. A46.3-A47
Author(s):  
Thomas J Keegan ◽  
Lucy M Carpenter ◽  
Claire Brooks ◽  
Toby Langdon ◽  
Katherine M Venables
Keyword(s):  
Pupil Size ◽  
Cholinesterase Activity ◽  
Biological Response ◽  
Chemical Warfare Agents ◽  
Nerve Agents ◽  
Chemical Warfare ◽  
Exposure Route ◽  
Warfare Agents ◽  
The Uk ◽  
Armed Services

BackgroundThe effects of exposure to chemical warfare agents in humans are topical. Porton Down, near Salisbury, is the UK’s centre for research on chemical warfare. Since WWI, a programme of experiments involving approximately 30 000 participants drawn from the UK armed services has been undertaken there.ObjectivesOur aim is to report on exposures to nerve agents, particularly sarin, using detailed exposure data in a cohort of servicemen who attended Porton Down.MethodsWe have used existing data on exposures to UK servicemen who attended the human volunteer programme at Porton Down to examine exposures to nerve agents in general and to sarin in particular.ResultsSix principal nerve agents were tested on humans, all between 1945 and 1987. Of the 4299 nerve agent tests recorded, 3511 (82%) were with sarin, most commonly in an exposure chamber, with inhalation being the commonest exposure route (85%). Biological response to sarin exposure was expressed as percentage change in cholinesterase activity and, less commonly, change in pupil size. For inhalation tests, assessed by changes in red blood cell cholinesterase median inhibition for was 41% (IQR 24%–51%), with a maximum of 87%. For dermal exposures, assessed by changes in unspecified cholinesterase, median inhibition was 22% (IQR 10%–37%), with a maximum inhibition of 99%. There was a clear association between increasing exposure to sarin and depression of cholinesterase activity but the strength f the association varied by exposure route and the presence of chemical or physical protection. Pupil size decreased with increased exposure but this relationship was less apparent when protection was present.ConclusionsThese results, drawn from high quality experimental data, offer a unique insight into the effects of these chemical agents on humans.AcknowledgementWe thank Nicola Fear and Gemma Archer, our collaborators in new work on these data, for their input.

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