β-AMINO ACIDS AND THEIR NATURAL BIOLOGICALLY ACTIVE DERIVATIVES. 5. DERIVATIVES OF UNUSUAL ALICYCLIC AND HETEROCYCLIC β-AMIMO ACIDS
2011, 2 - 11
α-Amino carboxylic acids are one of five major classes of natural products and play a crucial role in diverse biological functions. Historically, the amino acids have been subdivided into proteinogenic and nonproteinogenic respresentatives. β-Amino acids are similar to alfa-amino acids in that they contain an amino terminus and a carboxyl terminus. However, in β-amino acids two carbon atoms separate these functional termini. β-Amino acids, with a specific side chain, can exist as the R or S isomers at either the α(C2) carbon or the β(C3) carbon. This results in a total of 4 possible diastereoisomers for any given side chain. β-Amino acids are not proteinogenic amino acids, but some of them are constituents of soma natural and biologically active compounds.
Unusual β-amino acids are alicyclic β-amino acids and heterocyclic β-amino acids. Alicyclic β-amino acids, in which both the β-amino and the acids functionality are vicinally attached to an aliphatic ring, still represent a demanding challenge to the synthetic chemist. One reason for this lies in the intriguing difficulty associated with controlling the absolute and relative stereochemistry of two adjacent stereocenters. In heterocyclic β-amino acids the nitrogen of amino group is a part of nitrogen heterocycles. Some natural derivatives of alicyclic β-amino acids and heterocyclic β-amino acids, their chemical structures and biological activities are discussed in this mini-review.
A COMPARISON OF THE NEUROPROTECTIVE EFFICACY OF INDIVIDUAL OXIMES (HI-6, TRIMEDOXIME, K203) AND THEIR MIXTURES (HI-6 + TRIMEDOXIME, HI-6 + K203) IN CYCLOSARIN-POISONED RATS
Jiri Kassa, Jana Zdarova Karasova
2011, 12 - 20
The ability of three oximes (HI-6, trimedoxime, K203) to reduce cyclosarin-induced acute neurotoxic signs and symptoms was compared with the neuroprotective efficacy of two combinations of oximes (HI-6 + trimedoxime, HI-6 + K203) using a functional observational battery. Cyclosarin-induced neurotoxicity and the neuroprotective effects of HI-6, trimedoxime or K203 alone and HI-6 combined with trimedoxime or K203 in rats poisoned with cyclosarin at a sublethal dose (80 μg/kg i.m.; 70% of LD50 value) were monitored by the functional observational battery at 24 hours and 7 days following cyclosarin challenge. The results indicate that all types of antidotal treatment are able to survive cyclosarin-poisoned rats 7 days following cyclosarin poisoning while one non-treated cyclosarin-poisoned rats died within 24 hours following cyclosarin challenge. All three oximes alone as well as both oxime mixtures combined with atropine were able to slightly decrease cyclosarin-induced neurotoxicity in the case of sublethal poisoning but they did not eliminate all cyclosarin-induced acute neurotoxic signs and symptoms. Their ability to reduce cyclosarininduced acute neurotoxicity was almost the same regardless of type of antidotal treatment. Thus, the tested combinations of oximes were not able to increase the neuroprotective effectiveness of antidotal treatment of acute cyclosarin poisoning compared to the individual oximes.
Pavel Cech, Vladimir Bures, Karel Antos, Tereza Otcenaskova, Ales Macela, Petr Musilek
2011, 21 - 27
During emergency response operations many decisions have to be made. Information technologies provide possibilities for new tools to support decision makers in decisions that comprise of many critical factors and that require specialized knowledge. In these tools the complexity is tackled using modelling and simulations of possible scenarios of response operations. Today, conceptual modelling in the field of information technology is oriented on the ontological approach. Ontology is a shared vocabulary and an unambiguous machine processed specification of terms together with their relationships. The ontology can have the form of a taxonomy or classification, database schema or axiomatic theory. The ontological modelling can be utilized along with expert systems for decision support. Expert systems, in contrast to other approaches such as neural networks for instance, better reflect the domain knowledge and provide justification for the decision. The aim of this paper is to describe prerequisites and design general schema for decision support in response operations during biological incidents including the applicable technology.
CYTOKINESIS-BLOCK MICRONUCLEUS (CBMN) ASSAY/CBMN CYTOME ASSAY IN HUMAN LYMPHOCYTES AFTER IN VITRO IRRADIATION AND ITS USE IN BIODOSIMETRY
Jaroslav Pejchal, Vladimira Vasilieva, Milena Hristozova, Zdenka Vilasova, Jirina Vavrova, Mitko Alyakov, Ales Tichy, Lenka Zarybnicka, Zuzana Sinkorova, Vojtech Tambor, Klara Kubelkova, Jiri Dresler
2011, 28 - 37
Aim: Cytokinesis-block micronucleus (CBMN) assay and its comprehensive variant CBMN cytome assay are cytogenetic methods. CBMN is based on assessment of micronuclei in nucleated cells that have completed only one nuclear division. Besides micronuclei, CBMN cytome assay analyzes additional genotoxic (nucleoplasmic bridges and nuclear buds), cytostatic (nuclear division index), and cytotoxic
(amount of necrotic and apoptotic cells) parameters. The aim of this study is to evaluate these parameters in human blood lymphocytes after in vitro irradiation and to assess its contribution to biodosimetry. Material and methods: Human blood from 6 donors was in vitro irradiated by 0, 1, 2, 3, 4, or 5 Gy and cultivated for 72 hours. Blood lymphocytes were stimulated with phytohemagglutinin and their cytokinesis was blocked by cytochalasin B. After cultivation, cultures were hypotonically treated, dropped onto glass slides and stained with Giemsa. Slides were evaluated by microscope. Results: We observed significantly increased amount of micronuclei, nucleoplasmic bridges, and nuclear buds measured in binucleated cells, significantly increased amount of micronuclei measured in mononucleated cells and significantly decreased nuclear division index after irradiation by 1, 2, 3, 4, and 5 Gy. Amount of death cells (apoptotic and necrotic) significantly increased after irradiation by 4 and 5 Gy. Conclusion: Although all parameters assessed by CBMN cytome assay have biodosimetric potential, practically feasible is only evaluation of micronuclei in binucleated cells. This parameter was used to construct in vitro linear-quadratic dose-response calibration curve which could be used as a biodosimetric tool for triage of radiation casualties.
Jiri Patocka, Kamil Kuca
2011, 38 - 41
Phosgene oxime is an organic compound with the formula Cl2CNOH. It is a potent chemical weapon from the group of vesicants, specifically a nettle agent. Phosgene oxime is also known by its military designation, "CX". Phosgene oxime in both liquid and vapor forms causes severe pain and local tissue destruction on contact with eyes, skin, and mucous membranes.
Depending on the exposure, injury may be local or systemic. The effects of the poisoning occur almost immediately. No antidote for phosgene oxime poisoning is known. Generally, any treatment is supportive. Phosgene oxime is nonpersistent in the environment and not presents great bigger risk for animal nature.
2011, 42 - 43
From November 1 to November 5, 2010 I took part in a one-week Senior Medical Staff Officer Course at the NATO School in Oberammergau, Germany.
Oberammeragau is a small town with 5 000 inhabitants situated in the Bavarian Alps, near the wellknown ski resort Garmisch Partenkirchen. It lies in a very nice part of the Bavarian Alps, about 850 m above sea level. The current school building was used as army barracks as early as 1937 and during the Second World War it was converted to a factory where Messerschmitt aircrafts were produced. The facility has functioned as the NATO School since 2005. From November 1 to November 5 four parallel courses for different military specializations took place in the school. The total number of participants was more than 250. Fifty-six students from more than 30 countries participated in the Senior Medical Staff Officer Course.
Besides military medical service personnel, mainly physicians from NATO countries, military physicians from the Partnership for Peace countries were also present. The official language of the course was English. The aim of the course was to provide knowledge and detailed insight into NATO´s medical support policy. This included policy making in NATO, NATO medical doctrine, strategic force planning, multinational medical support options and relations with
Jan Misik, Ruzena Pavlikova, Jiri Cabal, Ladislav Novotny, Kamil Kuca
2011, 46 - 51
Usage and misusage of pesticides represent a health risk to military and civilian, especially to agricultural workers; also a possible terrorist threat is considered. The major route of low-volatility pesticides intoxication is percutaneous. Hence, skin permeation characteristics of pesticides are intensively investigated. In this study, in vitro measurement of skin permeation is presented on the example of pesticide paraoxon. Permeation experiments were performed in Franz-type of static diffusion cells using a pig skin. Paraoxon which permeated through the skin was determined enzymatically by modified Ellman‘s method. During 8 hours experiment, approx. 0.1 % of applied paraoxon has permeated through the skin. It was shown that pre-treatment by water simulating wet or sweated skin enhanced the paraoxon permeation.
Marie Vackova, Irena Hanovcova, Jan Smetana, Roman Chlibek, Vanda Bostikova , Miroslav Splino
2011, 52 - 57
The air does contains microbial agents originally coming from the soil, water, plants or animals, including men. Temperature, light and humidity are the basic factors which has influence of microbial survival and abundance. Different microorganisms travel by aerial transmission and are involved in serious processes causing pneumonia and other diseases.
In our study we decided to investigate microbial load in air at the Transplant Intensive Care Unit of the University Hospital of Hradec Králové, Czech republic for two years period. Air samples were taken from the patient’s breathing zone in the single rooms. Air was sampled with Biotest RCS Plus air sampler and material collected on the Total Count strips prepared with Tryptic Soy Agar.
The majority of air samples (54.2%) had microbial air load ≤ 100 CFU.m-3. Very low microbial air concentration from 15 to 30 CFU.m-3 was detected in the rooms before admission of new patients. Higher concentration was detected when medical staff was present in the room and investigation or treatment was carried out. The majority of microbial findings in the air were Gram-positive cocci (coagulase-negative staphylococci, Micrococcus spp., Sarcina spp.). Findings of Gram-negative stems were sporadic (Pseudomonas aeruginosa) as well as incidence of microscopic fungi (Cladosporium spp., Penicillium spp.).
Filip Zemek, Jana Zdarova Karasova, Kamil Musilek, Kamil Kuca
2011, 58 - 64
Plasma proteins such as human serum albumin (HSA) and alpha 1-acid glycoprotein (AGP) play an important role in the pharmacokinetic and pharmacodynamic properties of all endogenous or exogenous substances presented in the blood vessels. Their abundance in human blood not only helps to maintain hemostasis, but also makes them ideal candidates as transporters or possible depot reservoirs. Numerous
methods e.g. equilibrium dialysis, ultrafiltration. ultracentrifugation, high-performance affinity chromatography were introduced to determine potential interactions with plasma proteins and possible quantification.
In this work method was developed for the determination of drug-human serum albumin interactions and applied to obtain pharmacokinetic profile of AChE modulators prepared at the Faculty of Military Health Sciences. For method validation commercially used compounds HI-6 and obidoxime were chosen. HI-6 did not bind at all while obidoxime showed 7 % binding potency.
2011, 65 - 71
Sonography, thanks to the miniaturization, is increasingly widespread as a bedside examination technique in both hospital and prehospital emergency care. A number of protocols were set up for its effective and fast usage. The article briefly depicts this method and the requirements and ways of its application in the emergency care.
Jiri Patocka, Kamil Kuca
2011, 72 - 79
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.
Kamil Kuca, Kamil Musilek, Jana Karasova, Daniel Jun, Ondrej Soukup, Miroslav Pohanka, Kallol Kumar Ghosh, Martina Hrabinova
2011, 80 - 84
Searching for the universal oxime, which could be able to reactivate acetylcholinesterase inhibited by various nerve agents is still topic of high interest. In this contribution, oxime HLö-7, that was thoroughly discussed in the last decade, is evaluated . Its universality was tested in vitro using the rat brain homogenate as a source of the cholinesterases. The main members of the nerve agent family (tabun, sarin, soman, cyclosarin and VX) were used for this purpose. As shown, oxime HLö-7 was able to reactivate cholinesterases inhibited by all tested nerve agents with the exception of tabun. Hence, it could not be designated as the broad-spectrum reactivator.
THOMAS PROFT (ED.). MICROBIAL TOXINS: CURRENT RESEARCH AND FUTURE TRENDS. UNIVERSITY OF AUCKLAND PUBLISHING, NEW ZEALAND 2009, VIII + 192PP. ISBN: 978-1-904455-44-8.
2011, 85 - 87
Toxins are important virulence factors responsible for microbial pathogenicity. Potential applications of toxin research extend beyond simply combating microbial virulence and include the development of novel anti-cancer drugs and other front-line medicines. No less important is the use of toxins as tools in cellular biology and neurobiology. Understanding toxin molecular and cellular biology is critical for the development of new anti-toxin strategies, particularly for those with bioterrorism capability. This well worked book not only provides a general overview of toxins but elucidates in detail recent molecular approaches, achievements and refreshing perspective on the future studies of these molecules. The book is divided into nine chapters and each chapter is written by internationally respected scientists. ...
2011, 88 - 88
On 18th May 2011, a ceremonial committee meeting of the Society of Military Physicians, Pharmacists and Veterinarians of the Czech Medical Association of J.E.Purkinje was held at the Faculty of Military Health Sciences of the University of Defence in Hradec Králové. On that occasion the merited and outstanding representatives of military medicine were awarded honorary membership diplomas. The founding members of the Society COL (ret.) Assoc. Prof. RNDr. et PhMr Vladimír Měrka, CSc., COL (ret.) Prof. MUDr. Miroslav Špliňo, DrSc, and COL (ret.) Prof. MUDr. Josef Fusek, DrSc, dr.h.c., were awarded. In this way, the Committee of the Society ...
Vesna Jacevic, Goran Jokic, Viktorija Dragojevic-Simic, Dubravko Bokonjic, Slavica Vucinic, Marina Vuksa
2011, 90 - 96
The purpose of this study was to investigate the acute toxicity of sodium selenite in mice and rats after per os application to establish the relationship between a high toxic dose of sodium selenite and tissue alterations in rats. Increasing doses of sodium selenite (4, 10, 14 and 18 mg/kg) were administered in separate groups of mice and rats. Obtained LD50 values of sodium selenite in mice and rats were in the range of 8.08 to 12.11 mg/kg po. In separate groups of rats of both genders, sodium selenite in a dose of 10 mg/kg po was applied. Survived animals were sacrificed after the end of day 7 and an increase of fluids in thoracal and abdominal cavities was recorded. Tissue samples of the heart, liver, spleen and kidney were prepared using haematoxylin and eosin (H&E) staining. Histopathological examination revealed the signs of inflammation, haemorrhages, degeneration and rapid loss of normal cell architecture in the heart, liver, spleen and kidney of sodium selenite treated animals. These and other available data suggest the possibility of using environmentally friendly selenite rodenticide. These compounds which possess a different mechanism of action when compared to anticoagulants and an acceptable toxic potential, could improve rodent pest management programs, especially regarding anticoagulant-resistant rodents.
Jana Zdarova Karasova, Kamil Kuca, Daniel Jun, Jiri Bajgar
2011, 97 - 102
Human serum butyrylcholinesterase (BChE, EC 18.104.22.168) is currently under advanced development as a pretreatment for organophosphorus (OP) poisoning in human. It was shown to protect mice, rats, guinea pigs, and monkeys against multiple LD50 challenges of OPs nerve agents intoxications. The aim of this study was to verify the efficacy of the pretreatment by the human BChE in blood and brain after intramuscular intoxication by Russian VX agent (RVX). Purified human BChE was administered intraperitoneally (500 U/kg) 30 minutes before a single dose of RVX corresponding to 1 LD50 (15 μg/kg). Changes in cholinesterases activities were assessed by standard Ellman’s method.
In conclusion, BChE was not able to absolutely protect acetylcholinesterase against inhibition in blood. On the other hand it was able to reduce toxic effect of RVX in brain. The protection of cholinesterases in brain is important in prophylaxis, because brain damage is inconsistent with survival of intoxicated organisms.
Jan M. Horacek
2011, 103 - 117
Cardiotoxicity is a well-known and potentially serious complication of oncology treatment. Anthracyclines and high-dose chemotherapy especially regimens containing high-dose Cyclophosphamide represent the greatest risk. Early detection of cardiotoxicity is crucial for applying preventive and supportive therapeutic strategies. Various methods have been recommended for monitoring of cardiotoxicity. In our conditions, echocardiography and electrocardiography are routinely used. However, this approach shows low sensitivity for the early prediction of cardiomyopathy when the possibilities of appropriate management could still improve the patient’s outcome.
Recently, biomarkers of cardiac injury have been investigated in the assessment of chemotherapy-induced cardiotoxicity. Cardiospecific biomarkers, such as cardiac troponins, show high diagnostic efficacy in the early subclinical phase of the disease before the clinical onset of cardiomyopathy. The increase in their concentrations correlates with disease severity. As for natriuretic peptides, some studies, including ours, have shown promising results. Definitive evidence of their diagnostic and prognostic role in this context is still lacking and natriuretic peptides have not been routinely used for monitoring of cardiotoxicity in clinical practice. Other perspective biomarkers of cardiotoxicity in oncology are under study, especially heart-type fatty acid-binding protein (H-FABP) and glycogen phosphorylase BB (GPBB). Our studies using GPBB have brought priority and encouraging results. However, the available data are limited and their practical use in this context cannot be recommended until their clinical efficacy is clearly defined.
The author presents his own experience with multiple biomarkers of cardiac injury in the detection of cardiotoxicity associated with conventional and high-dose chemotherapy for hematological malignancies.
THE DISULFIDE BOND FORMATION AND ITS RELATIONSHIP TO BACTERIAL PATHOGENICITY OF THREE IMPORTANT GRAM-NEGATIVE BACTERIA
Iva Senitkova, Petra Spidlova, Lenka Hernychova, Jiri Stulik
2011, 118 - 128
Disulfide bond formation is necessary for a correct folding and a proper function of many secreted proteins. We know that many of these proteins are involved in bacterial virulence and pathogenesis. The best known pathways of disulfide bond formation and isomerization belong to Escherichia coli (E. coli). This Gram-negative bacterium is usually used as a model organism. This review is aimed initially at introduction to E. coli oxido-reductase enzymatic system. The next part is interested in proteins resembling these from E. coli and their relation to virulence and pathogenesis. We have choosen three important Gramnegative pathogens, Neisseria meningitidis (N. meningitidis), Yersinia pestis (Y. pestis) and Francisella tularensis (F. tularensis), because of their high virulence, infectivity, ability to cause severe infections and absence of appropriate vaccines.
Jiri Patocka, Ramesh C. Gupta, Kamil Kuca
2011, 129 - 139
Anatoxin-a(s) is a guanidinemethyl phosphate ester isolated from the freshwater cyanobacterium (bluegreen 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 22.214.171.124). 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. Anatoxina(s) induces clinical signs of hypercholinergic preponderance, such as salivation, lacrimation, urinary incontinence, defecation, convulsion, fasciculation, and respiratory arrest.
COMPARISON OF POTENTIAL CYTOTOXICITY AND GENOTOXICITY OF SELECTED ANTIDOTES AGAINST ORGANOPHOSPHATES INHIBITING ACETYLCHOLINESTERASE
Hana Svobodova, Petr Jost, Rudolf Stetina
2011, 142 - 149
Organophosphorous compounds cause fatal intoxication based on inhibition of acetylcholinesterase, an essential enzyme of neurosynapses and neuromuscular junctions. There is an obvious need to develop appropriate treatment against them due to their application in agriculture and chemical industry or their misuse in terrorist or war attack.
In the Czech army some medicaments have been established to be used against this poisoning; Obidoxime, Methoxime, Atropine and Benactyzine. In present in vitro study we focused on potential cytotoxic and genotoxic effect evaluation of these drugs by the clonogenic and comet assay, respectively.
Obtained results show that oximes exhibit pronounced toxic effect, namely obidoxime in term of genotoxicity and methoxime in term of cytotoxicity.
MULTIPLE MECHANICAL AND THERMAL BLAST INJURY IN CIVILIAN INDUSTRIAL SETTING – POSSIBLE PARALLEL TO THE BATTLEFIELD BLAST SYNDROME TYPE INJURIES
Leo Klein, Eduard Havel, Karel Smejkal, Jaroslav Cerman, Frantisek Hosek, Miloslav Hronek
2011, 150 - 158
A 43-year-old man, injured during a factory explosion on January 4, 2010, was transported to the nearest hospital. Volume resuscitation started, subclavian vein cannulation, chest tube, and covering of burns were performed. The intubated and ventilated patient was transferred by helicopter to our hospital. The leading diagnoses were: haemorrhagic – traumatic and burns shock, haemoperitoneum, pneumothorax, subtotal amputation of the left distal crus/feet, burns over 40 % of the body surface, right calcaneus fracture etc. Preliminary circulatory stabilisation with discontinuation of norepinephrine infusion was achieved within 10 hours, by excessive positive fluid balance, which took three days (22, 10 and 9 litres). Preliminary blood lactate 7 mmol/l was normalised within 24 hours. Blood albumin level 15 g/l was tolerated without any artificial replacement. The second hit appeared on day 10, in a form of septic shock caused by Aspergillus fumigatus infection from the lacerated left lower limb. High-volume continuous haemodiafiltration because of hyperpyrexia was used, after the exarticulation in the left knee-joint. An excessive proteolysis (urea loss more than 1000 mmol/day) persisted 1.5 months, with energy expenditure over 2600 kcal/day. The patient underwent multiple surgical interventions. Metabolic support using combined parenteral and enteral nutrition was performed during the first month, enteral nutrition combined with food were consequently given for more than 3 months. The patient was hospitalised until April 26, 2010. These types of traumas are fully comparable with military battlefield environment injuries. Principles of war surgery (life and limb saving, damage control surgery) should be applied also in civilian environment, particularly in disaster situations.
Libor Pisa, Radoslav Krupka, Veronika Formankova, Vera Neubauerova, Jiri Dresler, Martin Hubalek
2011, 159 - 168
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 10th 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.
Eva Novotna, Ales Tichy, Karolina Foltanova, Jirina Vavrova
2011, 169 - 177
The integrity of the human genome is constantly threatened by exogenous or endogenous genotoxic agents that cause DNA damage. The ionizing radiation (IR)-induced DNA double-strand breaks (DSBs) are considered as the most deleterious forms of DNA damage which could lead to genomic instability and to cancer development, if left unrepaired. The DNA damage response (DDR) is comprised of a network of proteins that cooperate to regulate cell cycle progression and repair of DNA lesions. Our understanding of molecular basis of repair processes and of functions of repair proteins, as well as understanding of chromatin modifications may provide new possibilities in improvement of cancer management. Phosphorylation of histone variant H2AX at serine 139 (γ-H2AX) and formation of γ-H2AX repair foci seems to be the most sensitive DNA damage marker in the chromatin flanking the free DNA double-stranded ends in DSBs. Monitoring of γ-H2AX levels can serve for early indication of cancer development, as biomarker of cancer therapy efficiency or as a biodosimetric marker of radiation exposure.
Vendula Sepsova, Jana Zdarova Karasova, Filip Zemek, Brian J. Bennion, Kamil Kuca
2011, 178 - 186
Acetylcholinesterase (AChE) reactivators (oximes) are generally used as antidotes in case of nerve agent poisoning. Because of their affinity to AChE, they may also act as weak inhibitors of AChE. Their inhibition potency against AChE was determined by an in vitro method based on the interaction between AChE and oxime reactivator in the concentration range 10-1 to 10-8 M. We used eel AChE for these assays. We found that AChE inhibition strongly depends on the oxime structure. The aim of the present study is to describe the structure-activity relationship (SAR) between oxime structure and inhibition of AChE. AChE reactivators tested include both monoquaternary and bisquaternary structures with the oxime group in different positions on the pyridine ring and with changes in the connecting linker in the case of the bisquaternary compounds. We found AChE inhibition to be highest in bisquaternary oximes that have a longer linker length and have the oxime group in the ortho position. Increased AChE inhibition in monoquaternary oximes was highest when the meta position was occupied by the oxime nucleophile. In addition, different substituents in the connecting chain (in case of bisquaternary oximes) modulated their inhibition potency.
2011, 187 - 188
The 11th Conference of the Society of Military Physicians, Pharmacists and Veterinarians took place at the Faculty of Military Health Sciences, University of Defence, in Hradec Králové, on the 18th and 19th October, 2011. The Society is a member of the Czech J. E. Purkinje Medical Association.
The main topics of the Conference were a) progress in diagnostics and treatment-procedures by military physicians engaged in primary care or practising in medical establishments b) practical problems of organization and command- and - control within the Service c) scientific activities and research in military health-care d) latest experiences in foreign missions e) selected casereports of special interest.
Altogether, 23 oral presentations and 13 posters were delivered. Presentations on the ethos behind the formation and development of the Military Medical ...