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A simple colorimetric biosensor, which uses the modified Ellman's reaction, enables selective analysis of nerve agents based on a different ability of bispyridinium oximes to reactivate enzyme-inhibitor complexes in the phase before dealkylation. The analysis was made based on spectral data of reflectance of the surface of a cotton cloth reaction zone of biosensor with immobilized and stabilized enzyme after inhibition and subsequent reactivation. The evaluation of measured data was made based on a method of artificial neuronal networks. The individual inhibitors from the groups of three nerve agents were identified: sarin, soman, tabun, cyclosarin, agent VX and its Russian analogue, R-33.

The treatment of organophosphate (OP) poisoning consists of the administration of a parasympatholytic agent, an anticonvulsant and an acetylcholinesterase (AChE) reactivator. Since there is no broad AChE reactivator available, a post-treatment strategy currently exploits administration of different types of oximes depending on the exposure of OP. In this contribution, we summarize all the available data about AChE reactivator HLö-7 including its synthesis, physico-chemical properties, pharmacokinetic and pharmacodynamics profile, and its efficacy in vitro and in vitro.

Traditional chemical weapon agents (CWAs) are known to bind acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Their lethality is known to be different for different mammalian species. We have modeled the binding affinity of CWAs to AChE and BuChE in human, rabbit, rat and mouse using molecular docking and free energy calculations. Through molecular docking we are able to correctly bind the CWAs at the active site. Using molecular mechanics generalized Born surface area (MMGBSA) calculations, we determined the binding free energy in the active site. Through these calculations, we observe that correct orientation at the active site is critical to binding.

Sternutators are substances that irritate the nasal and respiratory passages and cause coughing, sneezing, lacrimation, and sometimes vomiting. They are organoarsenic compounds and some of them were used as warfare toxic gases in World War I, namely diphenylaminochloroarsine, diphenylchloroarsine, diphenylcyanarsine, and phenyldichloroarsine. The effect of these irritants is in principle non-lethal.

New and modern techniques of drug design are extensively used in parallel or instead of the classic ones. Applicability of virtual screening (VS) is growing with the computational performance. This article includes list and short description of most frequent used methods in VS. These methods are divided into two groups - ligand-based VS and structure-based VS. Ligand based methods include chemical similarity, pharmacophore and quantitative structure-activity relationship. Molecular docking and scoring are methods of the structure-based VS.

Geneva, Switzerland, celebrated a most remarkable 90^th birthday jubilee. A highly respected Canadian surgeon who enjoys excellent mental and physical condition, and continues to perform the scientific and organizational work for which he has long been recognized throughout the world. A pioneer of medical emergency systems, Professor Gunn has contributed greatly to the emergence and evolution of Disaster Medicine, Humanitarian Medicine, and the expansion of surgical fields in developing and "third world" countries. He worked closely with officials for many countries and has continued this collaboration with Czech healthcare and medical educational institutions; most notably with Charles University in Prague and ...

The chemical warfare agents and neurotoxic agents are an important threat to people all over the world, and require special attention because they are highly dangerous. Most of these agents are neurotoxic organophosphorus compounds (OP), which inhibit the enzyme acetylcholinesterase (AChE), which is responsible for controlling the transmission of nerve impulses. To be inhibited by these compounds, AChE can sometimes be reactivated using cationic oximes, which are the most used substances for this reactivation. Until today there have not been discovered agents for complete treatment of poisoning by all OPs. For this reason, the treatment of intoxicated people requires the determination of the absorbed OP, in order to select the appropriate activator, a process that usually requires long time and may cause death. Therefore, this study aims to do a review on the OPs used as chemical warfare agents and the process of inhibition and reactivation of AChE, especially to motivate the development of new agents for defense against chemical weapons, a process that is very important for protecting all humanity.

World War I was a conflict where chemical warfare was first used on a massive scale. The earliest chemical attack occurred on the Western Front in October 1914 in Neuve Chapelle, but its effects were so minimal that the Allies learned about it only after the war from German documents. The attack in the Bolimow area, carried out by the Germans against the Russian army with artillery shells containing gas T (xylyl and benzyl bromides), was therefore the first attack on a massive scale recorded on the victim side. The attack, which occurred after it, made it possible to obtain some tactical success, but without a strategic breakthrough. Some of the later German attacks on the Eastern Front where chlorine was used proved to be more effective, but despite many victims there was not any major strategic success achieved. The Russians did not take attempts to use chemical weapons in the World War I.

The bubonic plague or black plague is a zoonosis, caused by the bacterium Yersinia pestis, which quickly infects a great number of people, being able to decimate entire populations. This characteristic has turned plague into a dangerous biological warfare agent since the 16^th century. Nowadays, the cure for plague is available; however the possibility of genetic engineering of Y. pestis strains could lead to the resurgence of this disease as a worldwide health problem of extreme gravity. In this work we have made a short resume and discussion on plague to provide readers with some information on its historical and clinical aspects, the currently used therapy and the potential of plague being used as a biological warfare agent nowadays.

The NATO Advanced Training Course on training for mass casualty situations was held in cooperation with Traumacenter Rambam Hospital in Haifa, Israel from November 16-18, 2009. In total, 22 participants from 8 countries of the Partnership for Peace and Mediterranean Dialogue Programmes attended the course. The participants, divided into three groups, discussed and practised scenarios of mass casualty management in the area of pre-hospital care, hospital care and use of non-conventional weapons. The international team of instructors used the following teaching methods: general lectures, guided discussions, use of advanced multimedia tools, tabletop drills, clinical simulations in a specialized center and a large-scale drill. The mass casualty drill was held at the end of the course. The trainees of the course also participated as observers and reviewers in the drill, and debriefed it together with Traumacenter medical staff. The course was made possible by the provision of a grant by the NATO Science for Peace and Security Programme.

The main goal of this reaserch is an evaluatin of mental stress. The level of stress was studied in a group of nurses that spent some time on the military missions, especially in Afghanistan.We used Meister questionary for evaluation of a stress level at work, in a civilian hospital in the Czech Republic and a military work place, during the mission.In conclusion, the goal of our reaserch is classification of a stress level during the nurses' deployment in foreign mission. Based on these results, some methods convenient for managing a higher level of stress were described and mechanisms of stress adaptation are discussed.

Group of viral hemorrhagic fevers (VHF) present a range of disorders from relatively moderately serious to human life threatening entities whose mortality reaches high levels. There are classified as acute viral febrile diseases characterized by nausea, myalgia and fatigue, dominating with general alteration of vessel permeability and regulation. Symptoms of bleeding often occur, particularly in severe cases which are usually diffuse and present a symptom of general vessel injury rather than life-threatening condition.

Riot control agents are highly potent sensory irritants of relatively low toxicity that produce dose and time-dependent acute site-specific toxicity. These compounds have been referred to as transient incapacitating agents or as lacrimators, and in common parlance they are known as "tear gases". These compounds interact pharmacologically with sensory nerve receptors associated with mucosal surfaces and the skin at the site of contamination, resulting in localized discomfort or pain with associated reflexes. This biological response, e.g. ocular irritation, results in pain in the eye and excess reflex lacrimation and blepharospasm. Riot control agents have both civil and military applications and have been classified as either military chemicals or chemical warfare agents. Non-lethal or less lethal weapons have become increasingly popular for law enforcement use when confronting dangerous, combative individuals in the field, include riot control agents. Many incapacitating agents were developed during the Cold War. Oleoresin capsicum (OC) spray, an extracted resin from Capsicum pepper plants, was first developed in the 1970s as an alternative to CS (2-chlorobenzylidene malononitrile) and CN (chloroacetophenone) agents. Most recently, a synthetic form of capsaicin, PAVA (pelargonic acid vanillylamide), gained popularity as a defensive aerosol in the early 1990s. Chemical, pharmacological, and toxicological properties of PAVA are discussed in this paper.

Anatoxin-a(s) is a guanidinemethyl phosphate ester isolated from the freshwater cyanobacterium (blue-green algae) Anabaena flos-aquae strain NRC 525-17. Previous work has shown anatoxin-a(s) to be a potent irreversible inhibitor of electric eel acetylcholinesterase (AChE, EC 3.1.1.7). Anatoxin-a(s) has been shown to be an active site-directed inhibitor of AChE, which is resistant to reactivation by oximes because of the enzyme-oxime adduct formation. In vivo pretreatment with physostigmine and high concentrations of pyridine 2-aldoxime methochloride (2-PAM) were the only effective antagonists against a lethal dose of anatoxin-a(s). Anatoxin-a(s) is very toxic and it is produced by cyanobacteria during its blooms. Purified toxin has an LD₅₀ (i.p) of approximately 20-50 μg/kg body weight in mice. Toxicoses associated with cholinesterase-inhibiting anatoxin-a(s) have been observed in humans, animals, birds and fish. Anatoxin-a(s) induces clinical signs of hypercholinergic preponderance, such as salivation, lacrimation, urinary incontinence, defecation, convulsion, fasciculation, and respiratory arrest.

Respiratory irritants are substances which can cause inflammation or other adverse reactions in the respiratory system (lungs, nose, mouth, larynx and trachea) after being inhaled. Depending on the type and amount of irritant gas inhaled, victims can experience symptoms ranging from minor respiratory discomfort to acute airway and lung injury and even death. The lungs are susceptible to many airborne irritants. A common response cascade to a variety of irritant gases includes inflammation, edema and epithelial sloughing which, left untreated, can result in scar formation and pulmonary and airway remodeling. There are hundreds of substances that can pollute air and harm lungs. Harmful gases and chemicals are just one type of airborne pollutants that can adversely affect the lungs. Examples of respiratory irritants include, for example, chlorine, amonium, ozone, sulphur dioxide or nitrogen oxides. These substances, their sources of exposure, physical and other properties, and effects on the victim are summarized in this article.

Many aldehydes are respiratory irritants which can cause inflammation or other adverse reactions in the respiratory system after being inhaled. Depending on the type and amount of irritant compound inhaled, victims can exhibit symptoms ranging from minor respiratory discomfort to acute airway and lung injury and even death. The lungs are susceptible to many airborne irritants. There are hundreds of substances that can pollute air and harm lungs. Aldehydes are just one type of airborne pollutants that can adversely affect lungs. Some of these agents may be directly toxic. They are also strong irritants for the skin, eyes, and nasal passages. The vapor is irritating to the eyes and respiratory tract. Aldehydes as acrolein or glutaraldehyde are also corrosive substances.

The Bulgarian Toxicological Society edited a book "Problems of Toxiclogy". This book includes reports which were presented at the Fourth National Congress of Clinical Toxicology with International Participation and Annual Meeting of Bulgarian Toxicological Society, which were held in Sofia, Military Medical Academy, Bulgaria, from 7th to 8^th November, 2013...

It is known that nerve agents are potent inhibitors of acetylcholinesterase (AChE), the enzyme responsible for the hydrolysis of the neurotransmitter acetylcholine and, thus, transmission of nerve impulses. The process of AChE inhibition by nerve agents can be reversed by a nucleophile able to dephosphorylate the enzyme. In this sense, oximes exhibit this characteristic and are able to remove the neurotoxic and reactivate AChE. Here, we review experimental and theoretical results involving docking and quantum mechanical-molecular mechanics hybrid methods (QM/MM), using Molegro^® and Spartan^® softwares to analyze the interaction of different nerve agents and oximes with AChE and to evaluate kinetic constants of reactivation.

This investigation deals with the affection of permeation of acetylsalicylic acid and paracetamol applied in the system propylene glycol-water 1:1 through full-thickness pig ear skin by alaptide that was applied in nanonized form as a potential chemical penetration enhancer. Alaptide, (S)-8-methyl-6,9-diazaspiro[4.5]decan-7,10-dione, is the original Czech compound. The application of nanonized alaptide significantly enhanced the permeation of both drugs through the skin. Enhancement ratios in the studied time interval 0.5-2.0 h varied from 1.11 to 17.70 for acetylsalicylic acid and from 6.83 to 19.83 for paracetamol.

Polymer drug delivery systems were during last few decades proven to be efficient potential therapeutics for cancer treatment, especilly for the treatment of solid tumors, where they may take advantage of the Enhanced Permeability and Retention (EPR) effect for tumor-specific passive accumulation. Controlled release of anticancer drugs in cancer cells may be triggered by. e.g., cathepsin B activation after endocytosis. Endosomal proteases, especially cathepsins B and L, are known to be one of the key factors influencing some viral infections. For instance Ebola virus requires partial proteolysis of its surface glycoprotein for efficient endosome escape within its life cycle. We hypothesize that polymeric cathepsin B and L inhibitors may utilize advantages of polymer delivery systems for more effective treatment of viral infections with cathepsin inhibitors reducing systemic toxicity and increasing efficacy by targeted delivery of these inhibitors.

The Institute of Molecular Pathology was founded on May 1, 1994 as a scientific centre of the Purkyne Military Medical Academy. During the twenty years of its existence the Institute has gained reputation of a qualified research centre focused on infection biology, clinical proteomic studies and biodefense. The advanced proteomics combined with cellular and molecular biology techniques and broad international collaboration have enabled the Institute to educate Ph.D. students at the highest possible level. Meetings, workshops, and conferences organized by the Institute have been attended by recognized scientists. The twentieth anniversary of the Institute foundation is a good opportunity to recap the results of its work.

Organophosphorus compounds (organophosphates and organophosphonates) exert their toxicity by phosphylating (i.e. either phosphorylating or phosphonylating) the serine hydroxyl group of the enzyme acetylcholinesterase (AChE) in its active center, thereby inhibiting this enzyme, which inactivates the neurotransmitter acetylcholine (ACh). This results in an accumulation of ACh and an "endogenous ACh poisoning".
Oximes, which can reactivate the inhibited enzyme by dephosphylation, are used in the therapy of organophosphorus compound poisoning. During the reactivation process, oximes become themselves phosphylated. Many of these phosphylated oximes are extremely potent AChE inhibitors, which may reduce their therapeutic efficacy.
K-27 is a very promising experimental oxime. In the present study, logP values of phosphylated K-27 are estimated after "in-silico exposure" to a number of organophosphorus esters [ethyl-paraoxon, methyl-paraoxon, diisopropyl-fluoro-phosphate, VX, soman, tabun, sarin, cyclosarin]. These logP values are compared with those of the native oxime and possible therapeutic relevance is discussed.
While our previously published data regarding obidoxime and pralidoxime show that phosphylation increases their lipophilicity, facilitating penetration into the brain where they can inhibit or re-inhibit enzymes, this conclusion does not hold with respect to K-27; phosphylation of K-27 does not generally increase lipophilicity. Possible consequences with regard to blood-brain-barrier passage, toxicity and therapeutic efficacy are discussed.

One possible use of CT navigated surgery in Otorinolaryngology includes traumatology of the facial skeleton.CT navigation enables a surgeon to assess the range and quality of reposition and fixation of a fracture, in our case the fracture of the orbital floor, using a navigated tube. We proceed from pre-operative CT of the paranasal sinuses images to navigation with 1,5-2,0 mm incisions and subsequent registration. Formerly, we used mainly transantral approach at our department, while currently we prefer subciliar approach with the use of absorbable materials (PDS or PMR splint).We use a rigid endoscope for infraorbital nerve decompression and delicate removal of free bone fragments from the maxillary sinus. We applied this procedure in 2 patients. We verified the range of decompression, degree of reposition of the orbital blow-out fracture, and placement of PMR splint and titanium grid using video navigation.

The deliberate use of chemical weapons has emerged as a significant threat especially in last decades, mainly after the terrorist attack on 11^th September 2011, and the use of these agents in future wars and terror attacks still remains a realistic concern. Despite the existence of many conventions and aggreements like Chemical Weapons Convention and 1925 Geneva Protocol against the use of chem-bio weapons, they have been used in many wars and conflicts. From this point of view, other than civilian state hospitals, military hospitals should be aware and get prepared to manage the victims injured due to chemical weapons. Military hospitals must be prepared to give support to health care system as well as military troops in treating and preventing casualties resulting from chemical weapons. Moreover, military hospitals are required to possess protective suits, masks, antidotes and other drugs. This article summarizes some important aspects which might be useful not only for military hospitals but also for civilian hospitals and public health organizations.

Anthrax is still a high threat biological agent, with historical precedence of potential terrorist use. While lack of human-to-human transmission may contain attacks in pockets, attacks can be multiple, coordinated and/or covert, therefore successful containment is heavily dependent on rapid identification after the smallest (possible) number of early cases, immediate and accurate statistical assessment of its geographic extent based on case histories, and a rapidly targeted prophylaxis strategy that considers both antibiotics and vaccine. Persistence of spores could lead to continued post-event threat, lack of guarantee that total decontamination has been achieved, fear of repeat attacks, concerns and disruptions to normal life, and tremendous loss to the economy. These considerations were among those that underpinned the recent 'Anthrax Counter Measures 2013' international conference held at the think-tank Royal United Services Institute, London, on 4 February 2013. Peer-reviewed abstracts of fifteen oral papers and nineteen posters presented in this conference are published as proceedings in this issue of the Military Medical Science Letters journal (ISSN 0372-7025). This meeting brought together academic, government and third sector organisations to debate key issues in anthrax counter measures under four themes: 'What might happen? How will we know? How to respond? What does the future look like?'. Topics explored include injectional anthrax (the latest and fourth mode of infection), inhalational anthrax (which drives biodefence considerations like animal models, emergency preparedness, etc.), the role of US government agencies post-Amerithrax attacks (especially the Animal Rule and Project BioShield, and the first licensed product raxibacumab), current and emerging trends in detection and diagnostics, etc. Discussions took place on how to accelerate products from laboratory to field, how to make the most out of the currently licensed antibiotics and vaccines, and how to bridge the gap between science and frontline response to anthrax. More efforts are needed to quantify the overall burden of the Amerithrax attacks, including the impact on tourism and business showdowns or diversions. This will enable governments to demonstrate value for taxpayer money and identify gaps through initiatives such as the annual preparedness index, shelf-life extension programmes, etc. Continued fiscal pressures could also encourage like-minded friendly governments to share resources and stockpiles, leading to other benefits such as increased resilience and cooperation.

Classical chemical nerve agents are organophosphate based compounds such as Sarin, Soman, Tabun, VX and others. These compounds inhibit acetylcholinesterases in the synapses of nerve junctions. Instead of inactivating acetylcholinesterases, compounds, quaternary amines, can block nerve transmission by binding primarily to the acetylcholine receptor sites. The U.S. Patent Office has published 23 unique patents or invention registrations on the synthesis of compounds that can bind to muscarinic and nicotinic acetylcholine receptors. It is likely that some of these compounds could serve as either polarizing or nonpolarizing nerve agents that bind to the acetylcholine receptor and block binding of acetylcholine. This paper has systematically reviewed a series of bisquaternary amines that could be potentially deadly nerve agents. Analogous tertiary amines, based on the structure of the parent bisquaternary amines, have been proposed as compounds that might be more soluble in membranes making them more bioavailable and toxic. Finally, methods have been discussed that could identify this class of compounds using a bioassay for binding to the acetylcholine receptor. A tool in the identification of these compounds, the Hofmann elimination reaction, has been proposed as a novel method for helping to establish that quaternary or tertiary amines are functional groups of the nerve agent.

The epidemiology of selected venereal diseases in the Czech Republic has been carefully evaluated for many years. This report containing data from the period 1981-2011 from the eastern Bohemia shows a sharp decrease in the incidence of gonorrhea in 1993-1994 and very low incidence thereafter with slightly higher prevalence in males. However, syphilis and genitourinary infection by Chlamydia trachomatis show entirely opposite trends. Also, for the similar number of diagnostic tests performed, chlamydia showed 10 fold higher ratio of positive cases. This underscores the changing epidemiology of STIs and necessity for adapting the reporting algorithms.

Surgical repair of inguinal hernias is one of the most common surgical procedures performed. Since endoscopic inguinal hernia repair was first reported in 1990, the operation has been refined into an attractive alternative to open hernia repair for many patients and surgeons. Transabdominal preperitoneal approach (TAPP) and total extraperitoneal approach (TEP) are the most commonly used methods for miniinvasive inguinal hernia treatment. Employing the electronic databases MEDLINE, Pubmed and Ebscohost, these methods were compared with open techniques. Perioperative and postoperative complications, recurrent hernias and quality of life were evaluated. For patients with bilateral inguinal hernia or with recurrent inguinal hernia, endoscopic repair offers significant advantages over open techniques with regard to pain, recurrence risk and recovery. For unilateral primary hernias, either endoscopic or open tension - free repair with mesh can offer excellent and equivalent results.

The production of safety food is the priority of developed countries. More than 25 % of worldwide production of cereals is contaminated with Fusarium fungi. Spoiled food/feed has a lower nutritional quality and also negative health effects. Fungi produce irritating volatile compounds, toxic compounds (mycotoxins) and allergizing spores. The most important metabolites from the toxicological point of view are mycotoxins. Several analytical methods are used for the detection of moulds in food/feed, urban dust or environmental samples. One of the most perspective methods is artificial nose which combines measurement using sensor array and signal evaluation using chemometrical methods, for example artificial neural networks.

Carbamates neurotoxins are a group of compounds acting as pseudo-irreversible inhibitors of an enzyme acetylcholinesterase and butyrylcholinesterase. The compounds are well known as pesticides. Some of them, such as rivastigmine, pyridostigmine, and neostigmine, can be used as drugs for Myasthenia gravis or Alzheimer disease as well. The present review is aimed to summarize the basic facts about carbamate pesticides. Legislative aspects, e.g. law No. 326/2004 Coll., in the Czech Republic and examples of accidental exposures to carbamates in the country are provided, too. Other general provisions are determined by the EU, in particular by the Directive 91/414/EHS. The European legislative is discussed, too. Finally, examples of accidental exposures are introduced in the study.