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In the early stage of drug development the solubility of drug candidate is the most crucial physicochemical parameter to be defined for the selection of lead compound. Conventional shake flask method of solubility determination has now been replaced with more precise measurements like ultraviolet absorption, nephelometry, nuclear magnetic resonance and potentiometry. The development of a simple, rapid, sensitive and precise spectrophotometric method for the routine quantitative determination of samples will definitely reduce unnecessary tedious sample preparations and the cost of materials and labour. This article accounts for the measurement of solubility limit of few selected drugs by spectrophotometry using dilution technique. This has been done to optimize the method for rapid and convenient determination of drug solubility limit. Concentration of saturated solution of drug was determined from the absorbance versus concentration plots of various diluted solutions of drug as per Beer-Lambert law and was reported as drug solubility limit.

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 kidneys are one of the organ that can be commonly damaged by a number of toxic compounds (heavy metals, xenobiotics, drugs, etc.). To characterize the mechanism of toxicity, a variety of methods have been developed. The in vitro methods belong among the mostly used. Especially, the use of cell lines seems to be the leading approach to test and to characterize the toxicity mechanisms. At present, several cell lines of animal (from rat, dog, pig) or human origin are available. A detailed evaluation must go before any selection of a suitable cell line for experiments. Therefore, the aim of this review was to describe and to evaluate the mostly used renal cell lines.

The 1^st International Conference << CBRN Research and Innovation >> co-organized by the French Alternative Energies and Atomic Energy Commission (CEA), the Armament procurement Agency (DGA), the Army Health Services, the Alpes-Maritimes Fire and Rescue Services (SDIS06) and Nice Conference Association was held in the Antibes-Juan-les-Pins Congress Center (France) from March 16 to 18, 2015 (www.cbrn-conference.com).Jean Leonetti, mayor of Antibes-Juan-les-Pins, member of the French Parliament, minister in charge of the European Affairs in 2011-2012, officially opened the Conference.The involvement of the Scientific Committee, a multidisciplinary group of 27 members...

The tetraethyl pyrophosphate (TEPP), the first synthetically prepared organophosphorus inhibitor of acetylcholinesterase, is put down to the French chemist Philippe de Clermont. Nevertheless, certain facts show that the first synthesis of TEPP was achieved by Clermont's colleague, likewise working in Adolphe Wurtz's laboratory in Paris. This person was a Russian student, Wladimir Petrovich Moschnine from Moscow. While Clermont was well known, nobody knew who Moschnine was. Due to young Portuguese researcher, Ana Carneiro, and Professor George A. Petroianu from the United Arab Emirates University, they managed to elucidated yet unknown history of organophosphate cholinesterase inhibitors.

Fecal microbiota therapy is going through its renaissance period. Even in ancient China, stool and its derivats were used for therapy of various diseases. Now thanks to new molecular methods a new knowledge about the intestinal microbiome and its interference with the human physiology, this method can be used for concrete therapy of disease.

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.

Together with the protection of the sick and wounded in armed conflicts, rules of international humanitarian law (IHL) provide protection to medical facilities and personnel. Despite universal acknowledgement of these rules, their violations occur regularly. Causes of these violations are numerous and complex, however, in order to be respected, IHL rules need to be in the first place implemented within domestic legislations of individual states. Specific measures to be taken are to a certain extent left up to discretion of every state concerned. This article examines existing legislation and measures adopted in this context by the national authorities of the Czech Republic with respect to the Czech Armed Forces. A particular attention is directed at internal regulations of the Armed Forces against the wider background of Czech legal order. The article also touches upon areas of military training and criminal liability.

Personnel decontamination belongs to one of the crucial measurements performed to personnel's protection within hazard management after either employment of Weapons of Mass Destruction or leakage of Toxic Industrial Materials. Suitable personnel, technical and material conditions corresponding to current demands and trends are necessary to create its realization in this area. Knowledge gained within solution problems of personnel decontamination, casualty decontamination, immobile people decontamination, decontamination of personnel weapons, selected Individual Protective Equipment, personnel garments, accoutrements and other materials with the usage of modular elements are summarized in this paper. A conceptual proposal of solution of a mobile decontamination system for personnel decontamination is also stated in this paper.

The University of Defence (UD) provides comprehensive education and training of students to get knowledge and skills which enable graduates to manage activities in the area of management and leadership. Formerly, the UD students received military and leadership skills especially within the military training outside the UD in basic training, in the Career course or the Specialized officer course at the Training Command - Military Academy (TC-MA) in Vyškov. Currently, the UD has included the Officer course into its own teaching curriculum, and thus bears a full responsibility for comprehensive preparedness of the UD graduates for their assignment to systemized positions in the Army of the Czech Republic (ACR).

MEDICAL COUNTER MEASURESE pidemiology, Health surveillance, Drug development, Comprehensive approachesDETECTION - IDENTIFICATION - DIAGNOSISHome-made explosives (HME), Improvised Explosive Device (IED), Field sampling & analysis, Skin biomarkers, Bioindicators & sensorsPROTECTION - DECONTAMINATIONHuman & environmental, Infrastructure, Smart surfaces & textiles, Skin, wounds, hair & eyes

The study was clinical, monocentric and prospective. The aim of the study was to elucidate the role and importance of hypocholesterolemia in polytrauma.Material and Methods: A group of patients, who sustained polytrauma (n = 19), were recruited to the study. We performed the determination of sterols plasma levels and their precursors (beta-sitosterol, campesterol, lathosterol, skvalen), interleukin 6 (IL-6) and cortisol in the blood serum. The short version of ACTH stimulation test was performed. The oxidative burst of granulocytes was evaluated. The blood samples were taken on the day of admission, the first, the fourth and the eighth post-operative and post-traumatic day.Results: There was a significant decline of total cholesterol (TC) and LDL cholesterol level with full recovery during observed period. There was a decline of cholesterol synthesis (lathosterol and lathosterol//cholesterol ratio) together with a decline of total cholesterol. There was a significantly negative correlation between IL-6 level and total cholesterol. Despite no confirmation of disturbance of adrenal function, there was a significantly positive correlation between lathosterol/cholesterol ratio (a de novo cholesterol synthesis marker) and cortisol level after the ACTH stimulation test. There was a significant breakdown of bactericidal function of granulocytes along with a decline of TC plasma level.Conclusion: There was decline of endogenous cholesterol synthesis in polytrauma injury. The cholesterol synthesis rate was negatively influenced by IL-6 level. The rate of endogenous cholesterol synthesis positively correlated with cortisol production by the adrenals and with bactericidal function of granulocytes.

Pralidoxime (2-PAM) is a monopyridinium aldoxime-type compound of acetylcholinesterase reactivators. 2-PAM was introduced about five decades ago for the treatment of organophosphorus poisoning in order to reactivate inhibited acetylcholinesterase. The application of organophosphorus compounds is varied, including warfare agents, insecticides and pesticides in agriculture, the chemical industry, etc. The exposure is not limited to certain groups of humans: rather everyone can be affected, including pregnant women, and consequently fetuses as well.The present study was aimed to determine the 2-PAM concentration in the plasma of pregnant mice, assuming a different physiological condition than non-pregnant ones. Blood-placenta penetration of 2-PAM was also investigated. 2-PAM was intraperitoneally injected into mice on gestational day 18 and mother blood was collected following 5, 15, 30 and 90 minutes. Four fetuses along with their placentas were collected at every time point. HPLC-UV method was employed to determine the 2-PAM concentrations. The result showed higher levels of 2-PAM at 15 minutes (t_max) in the plasma of pregnant mice compared to non-pregnant ones.Moreover, 2-PAM copiously reached the placenta, which is a store house of nutrients for the fetus. A higher concentration of 2-PAM was found in the brain of fetuses in comparison to that of the mothers'.Our study concludes that 2-PAM crosses the placenta barrier and reaches the brain of the fetus in a more ample quantity than that in the mother's brain. The results provide an insight into a special condition of pregnancy when antidotal application of the acetylcholinesterase reactivator 2-PAM in organophosphorus poisoning results in 2-PAM exposure in the fetus.

In February 2016, the World Health Organization (WHO) declared the current Zika outbreak a Public Health Emergency of international concern. The Zika virus disease is caused by a virus (family Flaviviridae) transmitted by Aedes spp. mosquitoes. People with the Zika virus disease usually have symptoms that can include a low-grade fever, maculopapular rash, conjunctivitis, arthralgia, malaise, headache and retro-ocular headaches. Neurological and autoimmune complications have been described during the outbreaks in Polynesia and recently in Brazil. There are no licensed medical countermeasures - vaccines, therapies or preventive drugs available for the Zika virus infection and disease.

Aim: To describe effectiveness of orlistat and phentermine in soldiers of the Armed Forces of the Czech Republic.Methods: In ambulatory patients, some anthropometric and biochemical parameters were compared before administration with 120 mg of orlistat three times a day or 15 mg of phentermine once a day. The same parameters were compared after a three-month therapy. This group included 289 patients (238 males and 51 females) who were administered the same dose of orlistat or phentermine for the entire period of time.Results: Statistically significant weight loss in both genders, on average by 4.6 ± 4.2 kg in males and by 5.3 ± 4.3 kg in females, was observed in patients taking orlistat within three months. Statistically significant weight loss, on average by 6.5 ± 6.0 kg in males and by 5.2 ± 4.3 kg in females, was also observed in patients taking phentermine for the same period of time. As for monitored biochemical parameters, a decrease of total cholesterol, HDL cholesterol and glucose at a statistically significant level (p<0.05) was observed in the group of females, the same statistically significant decrease, but in triglycerides, was proved in the group of males. Then a decrease of total cholesterol and increase of HDL cholesterol at a statistically significant level (p<0.001) was observed in the group of males.Conclusion: We can state that in our patients we have proven a positive effect of orlistat or phentermine substitution on their weight reduction.

The Syrian civil war is a shameful matter for the contemporary world. It is full of suffering for the civilian population and is one of the causes of the current huge migration of Syrian people in Europe. Suffering of people affected by the war is still escalating due to use of banned chemical weapons. The entire civilized world is appalled by the atrocities of the Syrian civil war.

The purpose of this work is to give a brief overview on history and main directions of work at the Department of Military Internal Medicine (DMIM). Chiefs (commanders) of the department are presented in chronological order together with tasks they had to deal with during a given period of time. A close cooperation of the DMIM with civilian hospital departments is pointed out, mainly in the areas of therapeutic and preventive care together with education. A departmental contribution to the development of the Military Medical Service is specified in detail, particularly surgical and non-surgical casualties support.

International terrorism becomes one of the most dangerous problems at the beginning of the 21^st century. Terrorist attacks have serious impact on politics, economy, military as well as security forces, international law and legislation, and psychological issues. International terrorism is legally characterised not only as a threat to the life and property of individuals, but also as a worldwide threat to human civilization, social order, international public order and values. The aim of this contribution is to specify the incidence of terrorist attacks from 1970 to 2013 in European countries and to characterise their imminent impact on the number of casualties. Furthermore, the contribution aims to specify the type of these attacks, weapons employed in them and numbers of casualties corresponding to various types of weapons. The analysis was based on data from databases and existing studies. The monitored period witnessed a slow but steady increase in the incidence of terrorist attacks in the EU countries without any significant changes. The types of weapons employed in these attacks did not change much, either.

The Department of Toxicology and Military Pharmacy (DTMF) as a part of the Faculty of Military Health Sciences, University of Defense was founded in 1951. During more than sixty years of its existence, the Department has gained reputation of a highly qualified research centre focused on the effects of chemical warfare agents (CWA), development of antidotes including antidotal means for the Army, solving questions with medical protection against highly toxic agents and educational activities, both pre- and postgradual including international cooperation. Meetings and scientific conferences organized by the Department have been attended by recognized scientists. Its future activities are focused on further studies and development of medical countermeasures including means against effects of CWA preferably nerve agents. There is real and concrete contribution of the Department to the improvement of medical protection of armed forces against the effects of CWA.

Viral hemorrhagic fevers (VHFs) represent a collection of illnesses caused by several distinct viral families. While some types of hemorrhagic fever viruses can cause relatively mild illnesses, many of these viruses cause life-threatening diseases. In general, the term "viral hemorrhagic fever" describes a severe multisystem syndrome. Typical for this syndrome is a systemic damage of vascular system often accompanied by hemorrhages.Ebola is a type of VHF, along with Marburg, Lassa, dengue, Rift Valley, and yellow fever. VHFs are RNA viruses whose survival is dependent on animal or insect hosts. Ebola hemorrhagic fever initially makes the leap from an animal reservoir to a human, and can then be passed from human to human through direct contact.In the autumn and winter of 2014 every day professional and popular press published new information about Ebola outbreak in West Africa. It was not just data related to the number of patients, new recommendations and protocols, information about testing of potential vaccines, but also theoretical works that tried to analyze the situation and data.

Currently, Biomedicine is characterised by a growing need for processing large amounts of data in real time. This leads to new requirements for information and communication technologies (ICT). Cloud computing offers a solution to these requirements and provides a lot of advantages such as cost savings, elasticity and scalability of using ICT.The aim of this paper is to explore the concept of cloud computing. Firstly, the forms of cloud computing are described. Secondly, the potential benefits and limitations of Biomedicine technology are discussed. Finally, the current (present) situation of using this technology in Biomedicine in the Czech Republic from an economic point of view is analysed.

A report about experiences gained during a month internship at the Queen Astrid Military Hospital Burns Centre in Brussels, Belgium, in May 2015.

One of the key requirements of the biodefense system of the Czech Armed Forces is a capability to identify the biological warfare agents (BWA). In this regard the Central Military Health Institute that is responsible for the biodefense in the Czech Armed Forces took part in 10^th Annual international comparative exercise of the NATO (North Atlantic Treaty Organization) military biological laboratories. The aim of this test was the identification of Bacillus anthracis in unknown samples which were contaminated by different disinfectants. Real-time polymerase chain reaction (PCR) was chosen as optimal method for this exercise because of a robustness, speed and flexibility of this method. Due to the presence of a disinfectant the identification procedure could only be conducted after including an additional step to sample preparation. Tandem mass spectrometry was selected as a confirmatory method for the exercise. Our test result was in full agreement with the exercise design. This exercise confirmed that method of provisional identification deployable in mobile component of biodefense system of the Czech Armed Forces is sensitive and robust for use in the field conditions. The tandem mass spectrometry analysis confirmed PCR results and verified the valuable confirmatory role of mass spectrometry in the identification of biological agents.

The beginning of participation of Czech troops in a modern history of crisis management abroad dates back to 1990, when the first 200 soldiers of the Czechoslovak anti-chemical unit deployed to Kuwait. The Armed Forces of the Czech republic (CAF) formed from the Czechoslovak Armed Forces in 1992, and from the very beginning kept sending out its troops to foreign operations. An important part of any contingent is its medical support, consisting of a physician (or physicians), field nurses and stretcher-bearers/ambulance drivers. Until the recent past, no resident physician has ever been involved in foreign operation. And there was no reason for that as the CAF used to have plenty of board-certified physicians available. A change occured in 2008 by the operation of a Provincial Reconstruction Team (PRT) assisting in Afghan Logar. This operation commenced in parallel with the ongoing operation in Kosovo, another major operation putting high demands on medical support. At the same time, residency training was prolonged to a period of five years. Lack of board-certified physicians therefore led to an idea of dispatching...

Poisoning from chemical warfare agents (CWAs) such as sarin is associated with neuronal degeneration. This damage is thought to result from glutamatergic excitotoxicity such as seen following kainic acid induced seizures. In order to search for novel neuroprotectants it is necessary to select good mouse models for susceptibility to nerve agent-induced seizures and the resulting neurodegeneration. The mouse strains tested (C57BL/6, ICR, DBA/2, SW, and FVB/N, Harlan Laboratory) had widely different sensitivity to sarin as shown by differences in the dose required resulting in 50% mortality, LD₅₀. Differences also were observed among the strains in Fluoro-Jade C staining with the C57BL/6 and DBA having little to no staining when euthanized at 7 days whereas the other strains did. Differences in acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activity were found among the strains as well. The ICR strain was excluded from the FOB and weight data due to difficulty getting a consistent LD₅₀. Weight loss and FOB scores were similar for all strains. All strains had inhibited AChE activity after sarin exposure and exhibited inhibition of CNS BuChE after sarin exposure but only ICR and SW reached significance.

Autoinjectors are commonly employed by the United States and other countries to deliver emergency therapeutics to counteract the effects of various chemical agent threats, including nerve agents. Autoinjector combination products (autoinjector and drug product) used by the military can have drawbacks, including insufficient thermal stability of drug products, limited aqueous solution concentration of active pharmaceutical ingredients (APIs), and complicated and expensive designs for delivering multiple drugs simultaneously. We have developed a novel Enhanced Formulation (EF) technology that solves these problems, using nanoparticle suspensions in biocompatible cottonseed oil (CSO) instead of aqueous solutions of API. The hydrophobic CSO prevents hydrolytic degradation by limiting exposure to water, and the noninteraction of co-suspended particles simplifies multi-drug cocktail therapies. The high API loading (10% or more) gives the formulations non-Newtonian rheological behavior, with high zero-shear viscosity to resist sedimentation, and shear thinning to allow injection with standard autoinjectors and needles.

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.

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.

The objective of the experiment was to verify that HI-6 dimethanesulphonate (HI-6 DMS) is able to penetrate the skin in amounts sufficient to protect against organophosphate poisoning using a rat model. HI-6 2Cl is a major component of Transant, a transdermal patch, used as a protective agent against organophosphate intoxication in the Czech and Slovak armies, although there is little evidence that HI-6 would penetrate the skin in sufficient amounts. HI-6 DMS at a total amount of 127 mg or 635 mg was applied as a buffer solution on the Transant patch which was fixed on the back of the rat. Two, seven or twenty-four hours later, rats were sacrificed and blood samples were collected to determine the levels of HI-6 in plasma by HPLC on reversed phase with isocratic elution and UV/VIS detection. HI-6 was not detectable in plasma samples of animals exposed to 127 mg of HI-6 DMS. The highest levels of HI-6 (20.6 ± 18.8 ng/ml) were found in plasma of animals exposed to 635 mg of HI-6 DMS 2 hours after patch application, whereas after 7 or 24 hours the levels were very low. Based on these results, the ability of HI-6 DMS to penetrate the skin is discussed and some possibilities of improving the transdermal penetration are suggested.