Vitezslav Vlcek, Miroslav Pohanka
2012, 2 - 8
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.
TOPICALLY-USED GENTAMICIN ATTACHED TO NANOFIBRE MDOCTM COMPARED WITH GARAMYCIN SCHWAMM® IN AN ACUTE WOUND INFECTION MODEL. AN EXPERIMENTAL STUDY.
Petr Lochman, Jiri Paral, Dusan Simkovic, Jaromir Koci
2012, 9 - 15
The aim of this study was to examine the effect of topically-used gentamicin attached to a biodegradable carrier, formed by micro-dispersed oxidised cellulose (MDOC) in nanofibre form, in acute wound infection treatment and to compare it with Garamycin Schwamm®. Twelve domestic swines were used in a model of a full-thickness infected dermal wound. The effectiveness of both materials in wound infections caused by Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli was tested. The effectiveness of both gentamicin with MDOC and Garamycin Schwamm® was comparable in Pseudomonas aeruginosa and Escherichia coli infections according to microbiological cultures findings. With Staphylococcus aureus infections there was a higher percent of negative cultures when MDOC with gentamicin was administered, but without statistical significance (p=0.069). When macroscopically assesed, 100 % of infected wounds treated by gentamicin attached to MDOC were without signs of local infection compared to only 16.7 % when Garamycin Schwamm® was used and this was statistically significant (p<0.01). For statistical analysis we used a Fisher´s exact test. When combined with a nanofibre MDOC carrier, topically-used gentamicin seems to be rendered more for treatment of full-thickness skin infections. The resulting good haemostatic effect of MDOC was observed.
Syed M Nurulain, M Shafiullah
2012, 16 - 26
Organophosphorus compounds (OPCs) are a wide group of compounds both structurally and functionally. Each OPC has a unique toxicological profile. The exposure to this type of poison is not limited only to certain occupationally exposed people but also to children, women, pregnant women; all have chances to be exposed to this poison. During the recent past years it has been reported in many poison epidemiological studies and case reports that exposure of OPCs during pregnancy caused malformed fetuses, neural tube defect (NTD) and shortening of pregnancy. The literature for animal models reveals inconclusive evidence. The generalized view is that they are neither teratogenic nor embryotoxic. But it is not true. There is a lack of systematic study and scarcity of reports on the topic. The present study was undertaken to investigate the teratogenicity induced by organophosphorus compounds in different animal models by literature review. Literature was searched by Toxicology Data NetWork (TOXNET), Developmental and Reproductive Toxicology Database (DART), Toxicology Literature Online (TOXLINE), Hazardous Substances Data Bank (HSDB), Pubmed Central, Entrez-Pubmed, Science Direct, Directory Of Open Access Journal (DOAJ), Google Scholar and International Program on Chemical Safety (IPCS-INCHEM), Embase. The terms for literature search were teratogenicity, organophosphorus compounds; fetal toxicity, organophosphorus compounds; organophosphorus poisoning and pregnancy; organophosphorus poisoning and growth restriction; organophosphorus poisoning and IUGR; organophosphorus poisoning and reproduction; organophosphates and reproduction; pregnancy and organophosphates. The outcome of the study concludes that the work on teratogenicity induced by organophosphorus compounds was completely neglected, inconclusive, and only carried out on less than half of the OPCs available in the market. A more comprehensive and systemic study on the subject is clearly needed and its importance should not be ignored because more positive cases are being reported on the teratogenicity and embryotoxicity of OPCs.
Adela Straskova, Jiri Stulik
2012, 27 - 39
Intracellular pathogen F. tularensis is a causative agent of tularemia disease and belongs to the most hazardeous pathogen worldwide, categorized by the Center for Disease Control and Prevention, USA (CDC) as a category A agent. However, no safe and licensed vaccine for prevention a F. tularensis infection is available for vaccination. Tularemia is manifested by several forms depending on a route of infection and virulence of a F. tularensis strain. Essential to a development of the disease is the ability to infect, survive and proliferate inside the mononuclear phagocytes, such as macrophages or dendritic cells. Therefore, this review will discuss aspects of F. tularensis intracellular fate within host macrophages, modulate host signaling pathways to benefit Francisella infection and finally, summarize bacterial determinats involved in the process of phagosomal escape and intracellular replication.
2012, 40 - 44
Natural cholinesterase inhibitors were found in many biological sources: bacteria, blue-greens, plants, marine sponges, microscopic fungus, and in a smaller scale also in mushrooms, fruiting body of macroscopis fungus. Only cholinesterase inhibitors isolated from mushrooms are subjects of this minireview. These natural compounds with anticholinergic activity may be considered as prospective drugs against Alzheimer’s disease.
FRANCISELLA TULARENSIS - 100 YEARS: TULAREMIA RESEARCH IN FORMER CZECHOSLOVAKIA AND IN THE CZECH REPUBLIC
Ales Macela, Jiri Stulik, Zuzana Krocova, Michal Kroca and Klara Kubelkova
2012, 46 - 55
The history of national tularemia research started in 1936 when the first outbreak was recognized in south-east Moravia. Since then in average about one hundred cases have been recorded annually. As tularemia was endemic in former Czechoslovakia, three research groups which concentrated on this disease were formed during decades. The first two groups have worked from sixties and were associated with Jiri Libich (Prague) and Darina Gurycova (Bratislava). The third group which concentrated on the research of natural foci started during late seventies in Valtice (Zdenek Hubalek). The experimental research was, and still is, mainly associated with military research, recently with the Proteomic Center (Faculty of Military Health Sciences, University of Defence) in Hradec Kralove. This center opens molecular approaches to the analysis of Francisella tularensis microbes on one side and the studies on mutual host-pathogen interaction on the other side. One of the significant aims of the research is searching for the new typing and diagnostic markers of Francisella tularensis for the military and medical practice. Thus, scientists from former Czechoslovakia and the Czech Republic contributed significantly to current knowledge on Francisella pathogenesis and their results were highly appraised by international scientific community.
Snezana Cupara, Slobodan Jankovic, Ivana Arsic, Vanja Tadic and Vesna Jacevic
2012, 56 - 60
External application of seabuckthorn oil (Hippophae rhamnoides L.) is difficult due to its liquid state in spite of its benefits for damaged skin. In order to overcome this inadequacy the semisolid emulsion with seabuckthorn oil was prepared. Previous research showed that this emulsion possessing an enhanced structure with liquid crystals showed a higher wound healing potential than seabuckthorn oil. The aim of this investigation was to characterize suitability of this emulsion for topical use. The emulsion was prepared by combining emulsifiers that form liquid crystals. Two different quantities of seabuckthorn oil were incorporated. Samples were prepared with 10% and 40% of seabuckthorn oil. Organoleptic characteristics were estimated visually and by smearing samples on a thin glass plate. Type of emulsion was determined by a conductometric method, while a pH value of the emulsion was measured by a pH meter. Samples of seabuckthorn emulsion were orange, semisolid, shiny, easily spreadable on skin, and the smear on the glass plate was homogeneous. There was an absence of smell and the emulsion could be rinsed by water after the application on skin, which is a desired characteristic of oil/water emulsions. Results of an electrical conductivity confirmed that an outer phase is water. Samples possesed an acceptable pH value for an external topical use. This research confirmed that constituents and a method used were suitable for preparing semisolid emulsion with seabuckthorn oil. Organoleptic properties, a pH value and a type of obtained emuslion appear to be adequate for topical use.
Jiri Patocka, Rene Pita and Kamil Kuca
2012, 61 - 67
Gyromitra esculenta (Persoon ex Fries) mushrooms have been responsible for severe intoxications and even deaths. Clinical data are characterized primarily by vomiting and diarrhea and after a while by jaundice, convulsions and coma. Other Gyromitra species which may be of concern are G. fastigiata and G. gigas; nevertheless, recent advances in chromatography, biochemistry and toxicology have established that other species within the Ascomycetes may also prove toxic. Their toxins, mainly gyromitrin (N-methyl-N-formyl-N-acetyl-hydrazone) and their higher homologues are converted in the milieu of human stomach into N-methyl-N-formylhydrazine (MFH), then into N-methylhydrazine (MH). The toxicity of these latter chemicals, which are mainly hepatotoxic and even carcinogenic, has been established through in vivo and in vitro experiments with cell cultures and biochemical systems. Considering the chemical structure and the reactivity of these natural compounds, chemical and biochemical mechanisms are defined in order to explain their intrinsic biological activity. These findings imply that consumption of G. esculenta could present a carcinogenic as well as an acutely toxic health hazard.
Jaroslav Pejchal, Jan Österreicher, Jiri Kassa, Vaclav Marak, Ales Tichy, Zuzana Sinkorova, Lenka Zarybnicka, Klara Kubelkova and Kamil Kuca
2012, 68 - 75
The purpose of our study was to examine an early activation of JNK and p38 mitogen activated protein kinases (MAPK) and their substrate c-Myc after soman poisoning in order to enlighten the pathogenetic mechanism of nerve agent-induced non-specific effects. Male Wistar rats were intramuscularly poisoned by soman (60 μg.kg-1 - 70% LD50). Samples were taken 4, 24, and 72 hours after poisoning, immunohistochemically stained and phospho-JNKThr-183/Tyr-185, phospho-p38Thr180/Tyr182, and phospho-c-MycThr58/Ser62 expressions were measured using a computer Image analysis in apical and cryptal enterocytes of the colon transversum. We observed decreased phospho-JNK in apical enterocytes 4 and 24 h after poisoning and increased phospho-JNK in cryptal and apical enterocytes 72 h after intoxication. Phosphop38 dropped significantly in the apical compartment 72 h after soman poisoning. An activation of c-Myc decreased in both apical and cryptal compartment 4 and 24 h after soman intoxication, while increased in both compartments 72 h after poisoning. Soman poisoning seems to temporarily suppress promitotic pathways of proliferating cryptal cells and causes delayed activation of JNK stress signaling pathway.
Jan Marek, Petr Stodulka, Ondrej Soukup, Kamil Musilek, Jiri Cabal and Kamil Kuca
2012, 76 - 81
Cationic tensides are a widespread group of surface active agents. These compounds have lots of applications in various branches of industry and research. Quaternary isoquinolinium salts differing in alkyl chain length are members of a cationic surfactant group with quaternary nitrogen in its structure. The members of this group can be used as micellar catalysts or disinfectants. Decontamination (chemical warfare agents) or disinfection (bacteria or fungi) for very similar compounds was described several times. In this work, the preparation of isoquinoline-derived cationic surfactants differing in the length of the side alkylating chain from C8 to C20 is described. An HPLC method used for distinction of all prepared long-chain isoquinolinium analogues has been successfully developed.
2012, 82 - 83
It was with great interest and pleasure that I read the contribution of Patocka et al. in the MMSL reviewing the literature on anatoxin-A(s) an Organophosphorus Cholinesterase Inhibitor (OP) of natural origin produced by cyanobacteria (formerly identified as algae). Anatoxin-A(s), a phosphate ester of imidazole (Figure 1), is a very interesting substance that lacking the ability to cross the bloodbrain-barrier selectively and irreversibly inhibits the cholinesterases ...
2012, 84 - 86
The story behind today’s training-system for doctors serving in the French Armed Forces is embedded in a series of establishments each of which has left its mark in history, maintained the closest links with centres of improvisation, and instilled in its students a deep sense of attachment.
It was at the very beginning of the 18th century that the first such establishment dedicated to military doctors appeared in France. It strove unceasingly to adapt itself not only to the needs of the military, but to the advancement and established use of knowledge pertinent to the changing conditions of military service.
Since then, piecemeal evolution finally resulted in the amalgamation of 2011 when, on the 2nd July, one single institution responsible for basic medical training was constituted --- the Defence School of Medicine (ESA). Its inauguration co-incided with the closure of the two Military Medical ...
Milan Ruzicka, Vojtech Humlicek, Petr Witt
2012, 90 - 95
In recent years, experience from the conduct of operations has shown changes in their contemporary leadership. Increasingly, asymmetric operations step to the fore. The medical support of these operations is one of conditions for their success. Results of exploratory research methods indicate the need for adjustments with regards to education, training as well as organization of medical support of the tactical units within asymmetric operations.
Jan Misik, Ruzena Pavlikova, Jiri Cabal, Denis Josse, Kamil Kuca
2012, 96 - 99
The purpose of this study was to assess the ability of selected detergents (althosan MB 50%, triton X) and one commercial decontamination mean (Argos™) to permeate the pig skin, which could indicate a potential toxic side effect of mass casualty decontaminants. A method of static diffusion cells and UV spectrometry was used to evaluate the skin permeation. All tested agents did not permeate the skin in detectable amounts as 5% water solutions. In concentrated form, triton X and Argos™ did not permeate the skin whereas althosan MB 50% shown specific permeation rate of 6.134 μg.cm-1 in 24 hours.
2012, 100 - 112
The most complex topic is represented by operative treatment of type IV lesions of rotator cuff. Palliative arthroscopic resection of rotator cuff did not produce optimal results. We thus intend to evaluate the newly implemented surgical techniques at our department.
Fifty-six patients with type IV rotator cuff lesions were treated surgically between October 2007 and December 2010. In 6 patients, combined operations had to be performed because of their pathology, and these were not included in detailed evaluation. The population selected for detailed evaluation of new surgical techniques included 50 patients (mean age: 59 years, range: 41–73 years). The patients were randomized into two subpopulations, each formed by 25 people. Both subpopulations can be considered representative and comparable.
All operations were performed in the “beach-chair” position in general anesthesia or/and in interscalenic block. After type IV lesion was diagnosed, the prespecified surgical procedure followed – partial muscle transfer of subscapularis muscle tendon (Karas) or partial non-anatomic rotator cuff reconstruction (Burkhart). The results were evaluated after 6 months using the modified Constant Functional Score. The following parameters were assessed: sex, age, side of the operation, dominance of the limb, Constant Functional Score pre-operatively and post-operatively, subjective and objective evaluation, pain, activities, movement and muscle strength, Constant Score improvement, improvement in its individual items and subitems, pain pre-operatively and post-operatively.
In older patients with type IV lesions, we have good experience with Karas method while in younger and more active patients, Burkhart method seems to be more useful.
POSSIBILITIES OF THE QCM METHOD EMPLOYMENT TO DETERMINATION OF TOXIC COMPOUND CONCENTRATION IN DEPENDENCE OF BARRIER MATERIALS RESISTANCE
Pavel Otrisal, Stanislav Florus
2012, 113 - 118
This paper points to some aspects of possible usage of a QCM method within a set of toxic compounds permeated concentration based on a permeation curves rate and after underdone calibration of a measurement system. Presented assesses can be used not only in favour of the Czech Armed Forces Chemical Corps specialists but subsequently also in favour of personnel protection for those working in an area with toxic compounds appearance.
EFFECT OF ACETYL-L-CARNITINE PRETREATMENT ON RADIATION PNEUMONITIS AND L-ARGININE-NO METABOLIC PATHWAY
Andrea Babicova, Jaroslav Pejchal, Zuzana Havlinova, Martina Rezacova, Klara Kubelkova, Jaroslav Chladek, Ales Tichy, Jirina Vavrova, Lenka Zarybnicka, Eva Novotna, Kamil Kuca, Zuzana Sinkorova
2012, 119 - 128
Purpose: The purpose of our study is to examine the effect of acetyl-L-carnitine (ALC) pretreatment on radiation pneumonitis and L-arginine-nitric oxide (NO) metabolic pathway after local chest irradiation.
Materials and methods: Female Wistar rats were pretreated with either phosphate buffer saline or ALC and locally irradiated by a dose of 15 Gy onto the chest. Samples were collected 7 weeks after irradiation. Exhaled NO was monitored using chemiluminiscence method. In plasma and bronchoalveolar lavage (BAL) fluid, nitrite/nitrate (NOx) and malondialdehyde were measured by high-performance liquid chromatography.
Total protein concentration was assayed colorimetrically. In lungs, inducible and endothelial nitric oxide synthase (iNOS, eNOS), arginase (Arg) I and II, cationic amino acid transporter (CAT) 1, 2 and 3 relative mRNA expression were measured by RT-PCR. Expression of Arg I and II was also evaluated by Western blot. Histochemical analysis was used to measure air/tissue ratio and neutrophil infiltration.
Results: ALC pretreatment increased survival rate of irradiated rats. It also decreased NOx concentration in BAL, while in lungs, we observed increased air/tissue ratio, reduced neutrophil infiltration, decreased CAT 1 and CAT 3 mRNA expression, and reduced Arg I and Arg II expression.
Conclusions:ALC pretreatment improves clinical prognosis and seems to reduce intensity of post-radiation changes on a molecular and microscopic level.
USING THE PIG’S BRAIN ACETYLCHOLINESTERASE IMMOBILIZED ON A TEXTILE FIBER TO TEST THE ANTIDOTES OF NERVE AGENT POISONINGS – PART I
Ivana Moravcova, Jiri Cabal, Jitka Sandova
2012, 129 - 137
An integral part of the research and development of new antidotes against nerve agents (herein referred to as NAs) is the verification of their efficacy by means of in vitro tests. The purpose of these tests is to verify the ability of an antidote to protect cholinesterases from inhibition or to reactivate inhibited cholinesterases. For this purpose cholinesterases of different species and with a different degree of purification are traditionally used. Using immobilized cholinesterases proves to be new and advantageous for a number of reasons. The authors of the presented work verified the usability of Detehit detector (Oritest Praha Ltd) containing the pig’s brain acetylcholinesterase for this purpose. In this article we see the results of tests focused on verifying the effect of different reaction conditions on the activity of acetylcholinesterase, especially with regard to reproducibility of these measurements.
2012, 138 - 139
On the 1st July 2012 the Center for Transfer of Biomedical Technologies (CTBT) started its operation at the premisses of University Hospital Hradec Kralove. The center provides intellectual property protection assistance and other commercialization support to researchers of University Hospital Hradec Kralove and partner organizations – Faculty of Military Health Sciences of University of Defence, Faculty of Informatics and Management and Faculty of Science of University Hradec Kralove. CTBT links industrial partners interested in commercializing ...
2012, 140 - 140
Organophosphorous compounds are the basis of many insecticides and nerve agents. In military and first responder situations, organophosphorous (OP) poisoning is treated immediately with nerve agent antidote autoinjectors. The specific antidotes contained within these autoinjectors vary by country. In certain situations, such as severe exposure, skin exposure to low-volatility nerve agents and protracted low-dose exposure, there is a requirement for in-hospital care of OP nerve agent poisoned casualties. This treatment is more effectively carried out using...
Jiri Patocka, Kamil Kuca
2012, 142 - 163
Toxic alcohols that clinicians commonly encounter are ethylene glycol, methanol, and isopropanol. Adults ingest these either for suicidal intent or to achieve inebriation, since these substances are readily available and cheaper than alcohol. Nevertheless, assorted alcohols are used very often in many applications and any alcohol can be toxic if ingested in large enough quantities. Toxic alcohols discussed here include all saturated aliphatic alcohols containing from 1 to 6 carbons in their molecules.
FROM THE RESEARCH OF CHOLINESTERASE REACTIVATORS TO THE EFFECTIVE THERAPY OF ORGANOPHOSPHATE/NERVE AGENT POISONING
Jiri Bajgar, Jiri Kassa
2012, 164 - 170
OBJECTIVES: The aim of this study is to inform about different techniques used to improve treatment of nerve agents intoxication at the Department of Toxicology.
METHODS: Different methods are briefly mentioned and their importance for development of more effective reactivators is discussed.
RESULTS: Basic characterization of nerve agents and therapeutic drugs is necessary after literature survey. Usage of different techniques and properties of various reactivators are studied and, on this basis, the most effective ones are tested in details and proposed for practical use.
CONCLUSIONS: The results described in this study clearly demonstrate that for the development of new and more effective cholinesterase reactivators, a complex approach using different methodical attitudes is necessary.
Jan Misik, Eva Vodakova, Ruzena Pavlikova, Jiri Cabal, Ladislav Novotny, Kamil Kuca
2012, 171 - 176
Detergent-based mixtures and pure surfactants used as decontaminants in mass casualty scenarios were investigated for their acute 24 h toxicity. Commercial detergents NeodekontTM, ArgosTM, DermogelTM, and FloraFreeTM were tested in male Wistar rats after percutaneous, peroral and intramuscular administration. Pure surfactants althosan MB, sodium alkylbenzene sulphonate, triton X, benzyl dimethyl dodecyl ammonium chloride, and N-dodecyl pyridinium bromide were investigated in male ICR mice. Estimated LD50 of surfactants varied from < 100 mg.kg-1 (i.m.) to more than 2000 mg.kg-1 (p.o, p.c.) in mice. All detergents tested in rats were rather less toxic (LD50 > 6 ml.kg-1), thus could be considered as safe if used as external skin decontaminant or if low volume is accidentally ingested.
Ales Tichy, Kamila Durisova, Eva Novotna, Lenka Zarybnicka, Jirina Vavrova, Jaroslav Pejchal, Zuzana Sinkorova
2012, 177 - 187
This review describes a drug target for cancer therapy, family of phosphatidylinositol-3 kinase related kinases (PIKKs), and it gives a comprehensive review of recent information. Besides general information about phosphatidylinositol-3 kinase superfamily, it characterizes a DNA-damage response pathway since it is monitored by PIKKs.
2012, 188 - 189
It has previously been shown that in methanolinduced toxic optic neuropathy with absolute blindness, recovery is rare, and almost never happens fully (1, 2). In other words, we have shown that after general management of acute methanol intoxication, patients with methanolinduced blindness can be grouped into three categories; 1: patients who are blind at the time of discharge and partially recover within a maximum of 3–4 weeks; 2: patients who are blind at the time of discharge and gain no improvement in their vision; and 3: patients who are blind at the time of discharge, partially recover within a few days to approximately 1 month, and experience reduced vision and blindness after about a maximum of 9 months (2) ...
THE 12th CONFERENCE OF THE SOCIETY OF MILITARY PHYSICIANS, PHARMACISTS AND VETERINARIANS OF THE CZECH MEDICAL ASSOCIATION OF J.E. PURKINJE IN HRADEC KRÁLOVÉ
2012, 190 - 191
The main topics of the Conference were current issues in the Military Medical Service organization and management, progress in diagnostics and therapy in military general practitioners and in hospital facilities, scientific and research work in military healthcare, latest experience in foreign missions and in pre-deployment training. In total 34 oral presentations were delivered and 15 high-quality posters were displayed. The latest news related to formation and development of the ACR Military Medical Service contemporary concept, particularly in consideration of economic restrictions on public budget, and about the Czech Armed Forces reform, attracted the close attention of all participants.