A Hidden Gem: Highlighting the Indispensable Capabilities and History of the DoD Cholinesterase Monitoring Program and DoD Cholinesterase Reference Laboratory.

The DoD Cholinesterase Monitoring Program and Cholinesterase Reference Laboratory have safeguarded U.S. government employees in chemical defense for over five decades. Considering Russia's potential deployment of chemical warfare nerve agents in Ukraine, it is critical to maintain a robust cholinesterase testing program and its efficiency presently and in future.

Guerra química en la I y II Guerras Mundiales / Chemical warfare in World War I and II

El objetivo de la presente revisión es analizar el uso de la guerra química durante las dos grandes guerras mundiales del siglo XX. La revisión de la literatura actual permitirá también conocer si las razones de su uso persisten en la actualidad, qué nivel de desarrollo han alcanzado las armas químicas y si existe potencial científico-técnico para incrementar dicho desarrollo. Para la elaboración del trabajo se llevó a cabo, en primer lugar, un procedimiento de búsqueda de artículos científicos y, en segundo lugar, se establecieron unas áreas temáticas para plasmar los resultados de dicha búsqueda (agentes químicos empleados, armas químicas utilizadas, efectos generales de los agentes químicos, riesgo químico y la posible defensa contra el ataque químico). El mal uso de la ciencia química ha dado lugar a estos tristes acontecimientos (la preparación y uso de armas químicas). Pero sería necesario contraponer otros muchos aspectos como los medicamentos, insecticidas, herbicidas, conservantes, desinfectantes, y otros, en los cuales la química ha sido la solución a complejos problemas que garantizan una importante mejora de las condiciones de vida. Como siempre, no es la química la culpable realmente; son dilemas éticos y sociológicos, mezclados con los dirigentes políticos, los que hacen que una ciencia sea utilizada de una forma responsable para bien de la humanidad o, todo lo contrario, que se utilicen los conocimientos como arma destructiva

The objective of this review is to analyze the use of chemical warfare during the two great World Wars of the twentieth century. The review of the current literature will also allow to know if the reasons for its use persist at present, what level of development chemical weapons have reached and if there is a scientific and technical potential to increase this development. First of all, a searching procedure for scientific articles was carried out, and, secondly, thematic areas were established in order to expose the results (chemical agents, chemical weapons, general effects of chemical agents, chemical risk and possible defense against chemical attack). The misuse of chemical science has given rise to these painful events (the preparation and use of chemical weapons). But it would be necessary to consider many other aspects such as medicines, insecticides, herbicides, preservatives, disinfectants, and others, in which chemistry has been the solution to complex problems that guarantee a significant improvement in living conditions. Once again, chemistry is not really to blame; they are ethical and sociological dilemmas, mixed with political leaders, that make a science to be used in a responsible way for the good of humanity or, on the contrary, as a destructive weapon

Phosgene use in World War 1 and early evaluations of pathophysiology.

World War 1 ended 100 years ago. The aftermath included the consolidation of significant advances in medical care of casualties. Some of these advances were made in the care of chemical casualties, in particular the mechanisms of toxicity and treatment of phosgene exposure. Phosgene, or carbonyl chloride, is an extremely poisonous vapour that was used to devastating effect during World War 1. Observations made of acutely poisoned casualties formed the basis of much research in the early post-World War 1 era. Some extremely elegant experiments, some at the nascent Porton Down research facility, further evaluated the toxin and defences against it. Researchers drew on knowledge that was later forgotten and has since been relearnt later in the 20th century and made many correct assumptions. Their work is the bedrock of our understanding of phosgene toxicity that survives to this day. The horrors of chemical warfare prompted the Geneva Protocol of 1925, prohibiting the use of chemical agents in warfare, and chemical warfare on this scale has not been repeated. The ease with which phosgene can be synthesised requires healthcare providers to be familiar with its effects.

Long-term neurological and neuropsychological complications of sulfur mustard and Lewisite mixture poisoning in Chinese victims exposed to chemical warfare agents abandoned at the end of WWII.

In August 2003, 44 victims were poisoned by chemical warfare agents (CWAs) leaked from five drums that were excavated at a construction site in Qiqihar, Northeast China. The drums were abandoned by the former Japanese imperial army during World War II and contained a mixture of Sulfur mustard (SM) and Lewisite. We carried out a total of six regular check-ups between 2006 and 2014, and from 2008 we added neurological evaluations including neuropsychological test and autonomic nervous function test in parallel with medical follow-up as much as was possible. Severe autonomic failure, such as hyperhidrosis, pollakiuria, diarrhoea, diminished libido, and asthenia appeared in almost all victims. Polyneuropathy occurred in 35% of the victims and constricted vision occurred in 20% of them. The rates of abnormal response on cold pressor test (CPT), active standing test (AST), Heart rate variability (CVR-R), performed in 2014, were 63.1%, 31.6%, and 15.9%, respectively. On neuropsychological testing evaluated in 2010, a generalized cognitive decline was observed in 42% of the victims. Memories and visuospatial abilities were affected in the remaining victims. Finally, a 17-item PTSD questionnaire and the Beck Depression Inventory evaluated in 2014 revealed long-lasting severe PTSD symptoms and depression of the victims. Our findings suggest that an SM/Lewisite compound have significant adverse consequences directly in cognitive and emotional network and autonomic nervous systems in the brain.

[Use of chemical war gases at the Russian-German front during the First World War].

The First World War was notable for the widespread use of machine military hardware and absolutely new type of weapon--chemical weapon. As a result of the first gas attack by chlorine undertaken by the German army against the Russian armies on May, 31st, 1915, heavy poisonings have received 9100 people, 6000 of them died. Chemical attack of Germany against Russia was limited by the use chemical gases of suffocating action: chlorine, bromine,phosgene and diphosgene. It is not known exactly, how many times Germany attacked Russian positions with use of chemical gases. On available data, in the First World War from application by German of the chemical weapon Russia has suffered more, than any other of the at war countries: from five hundred thousand poisoned have died nearby 66,000 people. In turn, having received in the order the chemical weapon of own manufacture, Russian army itself tried to attack in the German armies. It is authentically known only about several cases of application dy Russian of fighting poison gases, and in all cases of loss of germen were insignificant.

Neurotoxic Weapons and Syndromes.

The modern era of chemical and biological warfare began in World War I with the large-scale production and use of blistering and choking agents (chlorine, phosgene and mustard gases) in the battlefield. International treaties (the 1925 Geneva Protocol, the 1975 Biological and Toxin Weapons Convention and the 1993 Chemical Weapons Convention) banned biological and chemical weapons. However, several countries are probably still engaged in their development. Hence, there is risk of these weapons being used in the future. This chapter will focus on neurotoxic weapons (e.g. nerve agents, chemical and biological neurotoxins, psychostimulants), which act specifically or preeminently on the central nervous system and/or the neuromuscular junction. Deeply affecting the function of the nervous system, these agents either have incapacitating effects or cause clusters of casualties who manifest primary symptoms of encephalopathy, seizures, muscle paralysis and respiratory failure. The neurologist should be prepared both to notice patterns of symptoms and signs that are sufficiently consistent to raise the alarm of neurotoxic attacks and to define specific therapeutic interventions. Additionally, extensive knowledge on neurotoxic syndromes should stimulate scientific research to produce more effective antidotes and antibodies (which are still lacking for most neurotoxic weapons) for rapid administration in aerosolized forms in the case of terrorist or warfare scenarios.

Poison gas and thefirst World War: key role ofpharmacists.

Poison gas has been the subject of attention from the French army (Grand Quartier General). The 22sd of April 1915, General Joffre decided that the General Direction for Health Service was in charge of the protection of troops against what he called "this new mode of terror, disease, and death". Actions are been launched to found ways for the protection means and to obtain for the army at least equivalent weapons. Pharmacists will have a leading role thanks to their knowledge in chemistry. Research laboratories were working in two areas: individual protection and production of aggressive agents. Paul Lebeau, Gabriel Bertrand, Alexandre Degrez, Charles Moureu were among many others very committed to fight and remains at the top and to react quickly to ennemy's attacks. At the end of the war, Paul Lebeau received the Legion d'Honneur medal for his contribution to war. The school of pharmacy was recognized as faculty of pharmacy, by a decree of May 14th, 1920. The knowledge that were obtained during this period will be used for the second World War, but the chemical weapon was not much used, as opposed to more recent usage in Vietnam, Irak and Syria.

Pathology and Laboratory Medicine Support for the American Expeditionary Forces by the US Army Medical Corps During World War I.

CONTEXT: Historical research on pathology and laboratory medicine services in World War I has been limited. In the Spanish American War, these efforts were primarily focused on tropical diseases. World War I problems that could be addressed by pathology and laboratory medicine were strikingly different because of the new field of clinical pathology. Geographic differences, changing war tactics, and trench warfare created new issues. OBJECTIVES: To describe the scope of pathology and laboratory medicine services in World War I and the value these services brought to the war effort. METHODS: Available primary and secondary sources related to American Expeditionary Forces' laboratory services were analyzed and contrasted with the British and German approaches. RESULTS: The United States entered the war in April 1917. Colonel Joseph Siler, MD, a career medical officer, was the director, and Colonel Louis B. Wilson, MD, head of pathology at the Mayo Clinic, was appointed assistant director of the US Army Medical Corps Division of Laboratories and Infectious Disease, based in Dijon, France. During the next year, they organized 300 efficient laboratories to support the American Expeditionary Forces. Autopsies were performed to better understand treatment of battlefield injuries, effects of chemical warfare agents, and the influenza pandemic; autopsies also generated teaching specimens for the US Army Medical Museum. Bacteriology services focused on communicable diseases. Laboratory testing for social diseases was very aggressive. Significant advances in blood transfusion techniques, which allowed brief blood storage, occurred during the war but were not primarily overseen by laboratory services. CONCLUSIONS: Both Siler and Wilson received Distinguished Service Medals. Wilson's vision for military pathology services helped transform American civilian laboratory services in the 1920s.

[Consequences learned from the use of chemical weapons during the First World War for the modern military medicine].

The article describes the way medical service dealed with problems resulted from the use of chemical weapons during the First World War (1914-1918). It was revealed that many of the abovementioned problems remain unsolved up to the present moment. It is stated the existence of the threat of use of chemical weapons in modem military conflicts, which expands the area of responsibility for medical chemical protection. The authors proved necessity and algorithm of the training system, considered as a part of medical protection in case of adverse factors of chemical nature.

Modern toxic antipersonnel projectiles.

In the spring of 1944, Kurt von Gottberg, the SS police chief in Minsk, was shot and injured by 2 Soviet agents. Although he was only slightly injured, he died 6 hours later. The bullets were hollow and contained a crystalline white powder. They were 4-g bullets, semi-jacketed in cupronickel, containing 28 mg of aconitine. They were later known as akonitinnitratgeschosse. The Sipo (the Nazi security police) then ordered a trial with a 9-mm Parabellum cartridge containing Ditran, an anticholinergic drug with hallucinogenic properties causing intense mental confusion. In later years, QNB was used and given the NATO code BZ (3-quinuclidinyl-benzylate). It was proven that Saddam Hussein had this weapon (agent 15) manufactured and used it against the Kurds. Serbian forces used the same type of weapon in the Bosnian conflict, particularly in Srebrenica.The authors go on to list the Cold War toxic weapons developed by the KGB and the Warsaw pact countries for the discreet elimination of dissidents and proindependence leaders who had taken refuge in the West. These weapons include PSZh-13 launchers, the Troika electronic sequential pistol, and the ingenious 4-S110T captive piston system designed by the engineer Stechkin. Disguised as a cigarette case, it could fire a silent charge of potassium cyanide. This rogues gallery also includes the umbrella rigged to inject a pellet of ricin (or another phytalbumin of similar toxicity, such as abrin or crotin) that was used to assassinate the Bulgarian writer and journalist Georgi Markov on September 7, 1978, in London.During the autopsy, the discovery of a bullet burst into 4 or 5 parts has to make at once suspecting the use of a toxic substance. Toxicological analysis has to look for first and foremost aconitine, cyanide, suxamethonium, Ditran, BZ, or one of the toxic phytalbumins. The use of such complex weapons has to make suspect a powerful organization: army, secret service, terrorism. The existence of the Russian UDAR spray gun in the present day, however, shows that these weapons are still present. The possibility that one might be used to spray a charge of cyanide is still very real, especially as it would not be very difficult for an informed amateur to produce homemade toxic ammunition by adapting existing civil or military cartridges.

Overall view of chemical and biochemical weapons.

This article describes a brief history of chemical warfare, which culminated in the signing of the Chemical Weapons Convention. It describes the current level of chemical weapons and the risk of using them. Furthermore, some traditional technology for the development of chemical weapons, such as increasing toxicity, methods of overcoming chemical protection, research on natural toxins or the introduction of binary technology, has been described. In accordance with many parameters, chemical weapons based on traditional technologies have achieved the limit of their development. There is, however, a big potential of their further development based on the most recent knowledge of modern scientific and technical disciplines, particularly at the boundary of chemistry and biology. The risk is even higher due to the fact that already, today, there is a general acceptance of the development of non-lethal chemical weapons at a technologically higher level. In the future, the chemical arsenal will be based on the accumulation of important information from the fields of chemical, biological and toxin weapons. Data banks obtained in this way will be hardly accessible and the risk of their materialization will persist.

Iraq-Iran chemical war: calendar, mortality and morbidity.

OBJECTIVES: To review the calendar, mortality and morbidity of Iraq-Iran chemical war among Iranians based on researchers'reports. METHODS: We used national and international databanks such as PubMed, ISI, Scopus, Irandoc and Iranmedex and studied 350 articles related to chemical agents and their effects on different organs. The main criteria for qualification of articles were relevancy orientation and being published in approved medical journals. RESULTS: The Iraqi army invaded to west and southwest Iran using chemical weapons such as nerve agents (NAs) and sulfur mustard (SM). Most victims were civilians including women and children. These attacks had imposed more than 150 types of diseases and complications on Iranians and the frequency of death was 2%-3%. Most reports were about respiratory problems and a few were in the domain of socio-economic damages. CONCLUSION: At present, 25 years after the end of war, the victims are faced with different complications induced by chemical agents and it is estimated that they will be continuously troubled by these problems in future.