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Enzymes capable of degrading highly toxic organophosphate (OP) esters are emerging as safe and efficient means for destruction of nerve agent stockpiles, remediation of contaminated areas, decontamination of materials. Stoichiometric and catalytic biological scavengers are also promising alternative medical countermeasures against poisoning by nerve agents. Different OP-degrading enzymes are potential candidates for pretreatment, decontamination of skin, mucosa and open wounds or for treatment as supplement to current therapy. Here we will focus on human butyrylcholinesterase (BuChE, EC.3.1.1.8). Our goal is to engineer cholinesterase-based enzymes, having high OP-hydrolyzing activity, stable on storage and, stable in the bloodstream and immunologically compatible tobe injected in humans...

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.

Short-chain unsaturated aliphatic alcohols exist as volatile liquids, some of them are used in both industrial and non-industrial environments, and some of them are natural products of different organisms. These alcohols very often work as semiochemicals, including acting as pheromones, attractants, repellents, etc.. Long-chain poly-unsaturated alcohols are often toxic principals of certain plants, thereby presenting a risk to humans.

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.

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.

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.

Pregnant or postpartum patients with history of substance use disorder who desire to breastfeed present healthcare providers with numerous issues as drug use increases risk for adverse health outcomes for both the mother and her child. Drug use in the U.S. is common. In 2013, an estimated 24.6 million Americans aged 12 or older were current illicit substance users representing 9.4 % of the population. This statistic unfortunately closely corresponds with substance use in pregnant women. Totally 9% of pregnant women used drugs during their first trimester. Substance use during pregnancy and during breastfeeding presents serious problem for the health of our society. When a mother with a history of illegal/illicit drug use or illegal substance abuse desires to breastfeed, her healthcare providers are faced with several ethical dilemmas. The most obvious is whether she should be allowed to breastfeed her child. Does the benefit of breastfeeding outweigh the risk of possible substance transmission to the infant or is formula feeding safer and more appropriate option for the infant? What is the consequence of formula feeding on the fragile relationship between the newborn and the troubled mother? Lastly, the infant’s right to be breastfed needs to be taken into consideration as a part of this complex issue. Healthcare leaders need to be able to understand ethical challenges of this specific population, acknowledge variances between individual substances, and most importantly differentiate between occasional drug use, diagnosable substance use disorder and treated substance use disorder. Healthcare leaders should be able to clearly identify how to best provide the most effective and supportive care. Changes to policies and healthcare practices can advance the overall health of this specific and challenging population as well as can improve the relationship between these patients and their healthcare providers.

Study objectives: Varicella is a highly infectious disease, which is, however, preventable and an effective vaccine is available. Samples from a cohort of ambulatory and hospitalized patients (Faculty Hospital Hradec Králové) were analyzed as part of our molecular genetic study of varicella-zoster virus during years 2009 – 2016.Materials and methods: Altogether, 463 persons with varicella were younger than 18 years and 160 persons (25,7 %) were older. A total of 18 patients (2,9 %) were immunocompromised. Fifty patients reported the second incidence and 1 patient even third incidence of varicella.Results: Patients reported with varicella during the entire calendar year with two peaks in incidence - in winter (January, February) and late spring (May and June). This is contrary to the previous reports in literature, which describe this disease being seasonal in the temperate climate countries with a peak during winter months. While chickenpox is typically childhood disease in our country, we also report a detailed analysis of 160 adults.Genotypic analysis confirmed our previous findings and showed a higher prevalence of the European VZV wild type strains 2 (E2 - 65,6 %) compared to European VZV wild type strains 1 (E1 - 33,7 %).Conclusion: During the past eight years we have analyzed samples from a uniquely large cohort of patients treated on both the inpatient and outpatient bases in the Faculty Hospital Hradec Kralove. The size of the cohort, presence of patients from varying age groups and the availability of the clinical data, which can be correlated with the laboratory findings, all contribute to the validity of the results and bring additional questions for future studies.

Vaccination protects the community as a whole from serious communicable diseases, such as polio, pertussis, diphteria, measles and others. The incidence of these diseases has been successfully reduced in the last decades. Switzerland with its National vaccination strategy takes part in an international effort on public health described in WHO’s 2011-2020 Global Vaccine Action Plan (1), and in the European 2015 - 2020 Vaccine Action Plan (2). However, in contrast to the Czech Republic, Switzerland doesn´t have a compulsory global vaccination schedule. It only presents the vaccination recommendations. Vaccination rates are not always high enough in Switzerland and vary from one region to another.

On March 4, Sergei Skripal, a former Russian spy who was convicted and imprisoned in Russia for working as a double agent, and his daughter were found unresponsive and slumped on a shopping-center bench in Salisbury, England. On 12 March 2018, British Prime Minister Theresa May said in Parliament that the two had been poisoned with Novichok, a “military grade” nerve agent developed by Russia, and she moved swiftly to retaliate against the government of President Vladimir Putin (BBC News, 12 March 2018). It was the first use of a nerve agent on European soil since World War II. Russian authorities have rejected May’s claims as nonsense. On 14 March 2018, the UK expelled 23 Russian diplomats after the Russian government refused to meet the UK's deadline of midnight on 13 March 2018 to give an explanation for the use of the substance...

Cholinergic-regulated phenotypes including anxiety, cardiac and immune-related properties show inter-individual variability which might be affected by genomic Single Nucleotide Polymorphisms (SNPs) in the corresponding protein coding genes and their targeting microRNAs (miRs), but the combined impact of such SNP pairs is unknown. We have recently shown that the rs17228616 SNP in the Acetylcholinesterase (AChE) gene reduces the affinity of AChE mRNA to the primate-specific miR-608 and elevates both AChE levels in brain and blood as well as trait anxiety and blood pressure (1) while affecting PTSD-related neural circuits and downregulating numerous brain miR-608 targets (2). Others reported that the rs4919510 SNP in the miR-608 gene reduces miR-608 levels in vitro and limits the risk of sepsis following head injury in vivo (3). To explore the combined effect of these two SNPs, we tested 444 healthy 30 years old US donors and 101 Israeli ex-prisoners of the 1973 war (EWP), 76 of whom returned with post-traumatic stress disorder(PTSD). Genotyping combined with R-statistics of the corresponding biomedical evidence demonstrated that the rare allele of the AChE SNP was more abundant among non-PTSD EWP donors compared to PTSD patients in this cohort (33 vs 19%, Chi-square 0.03). Moreover, we found in both of these cohorts interaction between the effect of the two SNPs on blood pressure, inflammation and anxiety-related parameters, with the miR-608 SNP stratifying the corresponding impact of the rare allele of the AChE SNP on these parameters. Our findings indicate an interaction between the SNPs in the AChE and miR-608 genes, possibly reflecting modified impact of this primate-specific miR on its numerous downstream targets.

Nerve Agents are toxic organophosphorus compounds which inhibit cholinesterases, pivotal enzyme in Parasympathetic Neurotransmission. As they are Schedule 1 compounds in accordance to Chemical Weapons Convention, strict controls are applied and some research groups may have their work hampered due to requirements for synthesis and manipulation. Nerve Agents’ surrogates have emerged as affordable substitutes for more realistic approach for development of antidotes and biochemical and toxicity studies, as they are structurally related to Nerve Agents and considered as CWC Schedule 2 compounds, yielding similar enzyme adducts. As Laboratório de Análises Químicas – LAQ (ISO 17025) at IDQBRN have been participated in OPCW Proficiency Tests, striven to obtain the “OPCW Designated Laboratory” status, we have synthesized different dialkyl alkylphosphonates for verification purposes. Therefore, we have proposed synthesis of surrogates for our research on Medicinal Chemistry using them as starting materials. They have proven to be very useful compounds in our research and our syntheses have delivered good yields and purity of final compounds.

This review provides information about blistering chemical warfare agents. The main focus lies on the sulfur mustard. The article summarizes the history of this agent from its discovery to the present, physicochemical properties, toxicokinetics, and the clinical picture of acute intoxication. Late effects of poisoning are discussed as well. The laboratory diagnosis of sulfur mustard exposure is an issue that is currently being discussed by many research groups worldwide. Current therapeutic approaches recommended by NATO are aimed at rapid decontamination and symptomatic treatment. In spite of all efforts, no potent and usable antidote has been found to prevent the devastating outcomes of the exposure. Therefore, efficient protection against sulfur mustard still consists of preventing the contact with organism.

This article presents recent knowledge about galanthamine, its Structure, its pharmacodynamic as well as pharmacokinetic properties, its cognitive, behavioral and toxic efiects, and the methods of its determination in biological substances. _ This alkaloid is olatedfrom the Amaryllidaceae plant family acts as a reversible selective competitive acetylcholinesterase inhibitor and it also allosterically modulates the nicotinic acetylcholine receptors, thereby potentiates cholinergic, nicotinic neurotransmission. In medicine is has already been used since the 1960s, mainly in Eastern Europe to stop neuromuscular blockade and in neurological defect therapy. Recently galanthamine has been used predominantly for the treatment of Alzheimer’s disease because it significantly improves the cognitive, functional as well as behavioral symptoms of this disease. The selectivity of galanthamine to acetylcholinesterase against butyrylcholinesterase is favourable because this selectivity can decrease the risk of unwanted effects in comparison with the nonselective inhibitors of cholinesterases (tacrine, physostigmine). . We can assume that there will be an increased use of galanthamine in civilian as well as military medicine due to these properties.

MAIN TOPICS: News in vaccination 2014, Invasive bacterial diseases, Rotavirus gastroenteritis, Human papillomavirus diseases, Therapeutic cancer vaccines, Selected case reports in vaccination, Controversies in vaccination, Current problems of vaccination in selected diseases, Vaccination against exanthema diseases.

The circumstances of the WW II, paradoxically, contributed to the development of modern surgery of the hand, when General Norman T. Kirk, the US Army Surgeon General at that time, initiated establishment of centers for treatment of war hand injuries. Concurrently, he asked Sterling Bunnell, the author of the book Surgery of the hand, to train specialists in order to diminish number of disabled persons due to hand injuries. In 1946, nine leaders of those centers were among others who established the American Society of Hand Surgery, while Sterling Bunnell became its first President. Bunnell's influence exceeded the American continent noticeably. Some important representatives of hand surgery in Europe belonged among his pupils too. Remarkable progress of this special surgical discipline was achieved during the second half of the 20^th century (dynamic splinting after tendons suture, new methods of osteosynthesis, reconstruction using the microsurgical technique). By application of new technologies, tissue engineering and particularly when immunotoleration will be achieved, some another progressive development within surgery of the hand is to be expected in the future.

Giant hogweed (Heracleum mantegazzianum) is a member of the parsley or carrot family (Apiaceae). As its name indicates it is characterized by its size and may grow up to 4 meters in height. Giant hogweed is native to the Caucasus mountains and southwestern Asia and has been introduced to Europe, the United Kingdom, Canada and the United States as a garden curiosity. Because of its tenacious and invasive nature it soon becomes a pest within the ornamental garden and readily escapes. It has naturalized in many of the places where it was first introduced. All parts of the plant are poisonous and giant hogweed is toxic to livestock and humans. The danger of this contact-poisonous plant lies in the presence of phototoxic furocoumarins (psoralens). These substances cause disagreeable dermatitis with poorly healed blisters. Giant hogweed is dangerous for children and mainly if its juice penentrates the eyes.

Plant tropane alkaloids atropine and scopolamine are very strong anticholinergic drugs used in medicine and also found their place in military medicine, in particular atropine as an antidote in case of poisonings by nerve gases. Atropine and scopolamine both easily penetrate the blood-brain barrier and may cause central nervous system toxicity. Its symptoms are delirium, restlessness, confusion, and impairment of mental capacities. Scopolamine is much more likely to produce sedation and amnesia than atropine. Synthetic atropine-like compounds are also strong anticholinergics, and found use as a modern type of chemical weapons that incapacitate enemy for some time, but do not kill him. They are so-called non-lethal weapons, which are able to temporarily disable personnel from combat action and to protect the environment without limiting desired negative consequences to the enemy's national economy. Such non-lethal weapons is Agent BZ.

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.

Knotweeds (Reynoutria Houtt.) are plants native to the Far East. Japanese knotweed was introduced from Japan to the unsuspecting West by the horticultural activities of Philippe von Siebold via his nursery at Leiden in the 1840s. By 1854, the plant had arrived at the Royal Botanic Gardens in Edinburgh. The plants were then sold by a large number of commercial nursery gardens around the country. Further vegetative spread followed naturally along watercourses. The knotweed is currently extremely persistant invasive plant. There is also an important source of many bioactive substances which could be used in biomedicine. The article discusses biomedically relevant constituents and its pharmacological and toxicological properties.

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.

Soldiers, particularly those involved in combat operations, are exposed to a continuous danger frequently resulting in various types of injuries, out of which the most common and serious is traumatic brain injury (TBI). Up to the second quarter of 2015, the Defense and Veterans Brain Injury Center has recorded 333,169 cases of active soldiers affected with TBI. TBI can be defined as an injury that results from external force to the head and causes an alternation of loss of consciousness. The key symptoms of TBI comprise physical problems, sensory impairments, behavioral changes, cognitive disorders, communication difficulties, and swallowing disorders. The purpose of this study is to review available studies on TBI among active military personnel with special focus on communication disorders. The methods applied for this study include a method of literature review of both clinical and review studies relevant for the researched issue in the acknowledged databases and a method of comparison and evaluation of their findings. The findings show that the research studies exploring communication disorders among the active military personnel are rare. In addition, earlier diagnosis of TBI is needed as well as a multidisciplinary team intervention approach to the treatment of TBI.

The military incapacitating agent BZ (3-quinuclidinyl benzilate) is an anticholinergic compound that acts at both, the peripheral and central nervous system. Effects of the agent were discovered during the Cold War and BZ became one of the most potent anticholinergic psychomimetics, characterized by low effective doses causing long-term incapacitation. History, characteristics and potential use of BZ in behavioral research are discussed throughout this review.

Hyperforin is a prenylated phloroglucinol derivative which occurs in the plant Hypericum perforatum L. It has several medicinally important properties (antidepressant, anti-inflammatory, proapoptotic, antibacterial and antiangiogenic). To enable its medicinal use, it is necessary to investigate its potential genotoxic effect on human cell lines. We also observed an anticlastogenic effect of hyperforin towards the indirect mutagen benzo(a)pyrene. Benzo(a)pyrene is a widespread polycyclic aromatic hydrocarbon. We performed experiments on human tumor cell line HepG2, using the in vitro mammalian chromosome aberration test. We investigated two cytogenic parameters: the number of aberrant metaphases and the total number of chromosome aberrations. We found out that hyperforin was not genotoxic on human cell line HepG2. The second part of our results implies that hyperforin had an anticlastogenic effect against the indirect mutagen benzo(a)pyrene in our experimental conditions. In future we will continue our research by using another range of hyperforin concentrations, other cell lines and other chemical mutagens.

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.

Beauveria bassiana is a fungus which causes disease in insects. Currently it is used as an insecticide to control pest populations. Fungi are known to produce a vast array of secondary metabolites that are important for biotechnological applications. Furthemore, B. bassiana is an interesting source of biologically active molecules. There are alkaloids with the structure of 2-pyridone, dibenzoquinone pigments and different cyclodepsipeptides. Cyclodepsipeptides from B. bassiana are interesting for their neuroprotective properties. Interest of psychopharmacology is focused on the group of beauveriolides. Plant B. bassiana becomes a candidate for the prevention and treatment of neurodegenerative diseases.

International terrorism is rightly regarded as one of the greatest threats to world security and stability. Terrorist attacks that have occurred in recent years around the world have highlighted the need for a comprehensive approach. Formulation of the problem is a prerequisite for successful work, but the main problem is that there is no single definition of terrorism. View on possible definitions and important concepts are mentioned in this article.

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.