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The aim of the study was to evaluate models for studying possible preventive effects of selective antioxidants on biochemical changes induced by chronic intrauterine hypoxia and neonatal anoxia in Wistar//DV rats. Anoxia of newborn rats and chronic intrauterine hypoxia induced by phenytoin caused oxidative stress followed by organ ischaemia/reperfusion and reactive oxygen species generation. In biochemical quantification of oxidative stress we used the activity of the lysosomal enzyme N-acetyl-B-D-glucosaminidase (NAGA) and the level of glutathione (GSH) in foetal liver and brain, and in the placenta and brain, lungs and liver of newborn rats as markers of tissue damage. Neonatal anoxia (25 min) in 2-day-old pups induced significant increase in NAGA activity in lungs and liver and GSH increase in brain and liver. The activity of NAGA in brain....

This study was carried out to evaluate whether the pyridoindole stobadine (STO), which is an effective cardioprotective drug and a potent antioxidant, had any specific role in changes Of lysosomal enzyme (LE) activity in the rat heart during oxidative stress induced by a high dose of a synthetic catecholamine, isoproterenol (IPN). Oxidative stress induced by catecholamines is a well recognized toxic event. This effect has been extensively observed in the heart, where high levels of catecholamines cause lipid peroxidation, energy depletion and myocardial necrosis accompanied with leakage of lysosomal content and subsequent LE activity changes in most mammals. The activities of the LE acid phosphatase and N-acetyl-ß-D-glucosaminidase were studied in the rat heart as markers of cell damage. IPN-induced toxic damage in male Wistar rats (9 h after IPN hydrochloride administration, 50 mg/kg s.c. ) was manifested by marked alterations in the activities of the LE in the sedimentable fraction of the rat myocardium. STO administered in various dosage regimens reduced or diminished the IPN-induced biochemical changes in the rat myocardium. The results suggest that STO is able to protect rats against IPN-induced oxidative stress.

The authors summarize the results of six year’s study on genetic resistance of organism to the infection that were obtained using a various experimental models. The findings are shown in broad context of genetic regulation of diseases including their rise and development. Individual susceptibility to the disease is controlled by expressed genes. The genetic control influences both the primary interactions of external signals with the cells or molecules of immune system and the mechanisms of adaptive immune response. The changes in immune responsiveness can lead to the reaction of host defence mechanisms with the selfantigens and cause the autoimmune disease. Present mapping of human genome allows better knowledge of the building elements of the homeostatic mechanisms that are necessary for keeping of integrity of the organism. To achieve this aim, we need deeper understanding of the mechanisms of the disease at the molecular level. This molecular pathology belongs to the permanent interests ofthe authors.

The stressogenic effect of highly toxic organophosphate sarin following single or repeated inhalation exposure to low doses of sarin by monitoring the corticosterone level in plasma, the tyrosine aminotransferase activity in liver as well as the level of catecholamines and their metabolites in the brain was studied in rats.
While the statistically significant increase in the level of some stress markers at three and twelve months following the inhalation exposure not only to symptomatic but also to asymptomatic doses of sarin was observed in comparison with the control values, no changes in stress markers at six months following the inhalation exposure were demonstrated in sarin exposed rats in comparison with the control values.
Therefore, our results confirm the possibility of long-term stressogenic effects of sarin following low-level exposure in rats, although these effects were not observed at all time intervals studied.

Effects of sarin, soman and VX were described and discussed. The trigger mechanism of their action is inhibition of cholinesterases followed by non-specific changes. However, changes in cholinesterase molecular forms are of interest and they play an important role in mechanism of action of nerve agents, too.

The work analyzes biodosimetric methods used in experimental and clinical practice. Furthermore, authors inform about possible biodosimetric markers based on results of recent research, which could be developed within midle-term time.

Domoic acid, an amino acid produced by some microscopic algae and diatoms from the sea phytoplankton, causes toxicity in some sea animals, especially shellfish. Their consumption can cause curious intoxications combined with neurodegeneration and central nervous system dysfunction. In many cases a loss of recent memory occurs. It means a reduced capability or an absolute inability to remember new knowledge. Our study presents basic information on this strange excitotoxin.

The study compares the radiosensitivity of some haematopoietic tumorous cell lines. It proves that the cells of TP-53 negative leukemic line HL-60 are imprisoned before the entrance into apoptosis in the G₂ phase of the cellular cycle after doses of ionizing radiation up to 10 Gy. Massive apoptosis appears after a dose of 10 Gy as late as 48 hours after irradiation.

Modern medicine seeks new paradigms in a number of areas. In many areas in this connection gradual atomization occures and in some areas there is even the danger of a loss of needed continuity among the medical branches. Often discussed health problems of a human being in connection with his or her extensive exposure to xenobiotics in the environment and a bad life-style together with the recently passed Law number 258/2000 of the Digest (which is a basic medical law solving in an acceptable way the questions of primary prevention in a rebuilt system of health services and health care) were stimuli for writing this contribution.
Primary prevention is very important in the work of each health service worker and especially each physician. However, everyday experience has not been very encouraging and elementary institutionalization of this area, at least including a legislative part, is a must. Transparent limitation of associated esponsibilities, competencies, sanctional authorities and professional links to the appropriate institutions of higher administration areas or central institutions concerning methodical guidance or arbitration is necessary.
The author expresses his convinction that this is a unique chance to use the transformation of the hygiene service (which is in progress) to build (without uncritical copying Of foreign models) an institutionalized system of primary prevention based on our experience, complying with our needs and adequate to our possibilities and that this opportunity should not be lost. The outlined problems of the future require, when respecting the specific features of hygiene and epidemiology, their barrier-free cooperation. As it is possible to document from experience in other fields, the most rapid progress and most interesting problems can be expected in the area of their mutual overlap, including for example methodical applications of molecular toxicology. in the environmental epidemiology. It is also possible to expect a fundamental extension of the applications of epidemiology approaches in clinical studies. Primary prevention of diseases with mass incidence and by this an effort to positively influence the quality of human life remains in the centre of interest of both branches.

The article presents changes in selected daily work and rest activities, subjective assessment of health status and well-being, and risk behavioral factors in schoolchildren from aspects of primary preventive health care. The daily activity data, obtained on the basis of a 7-day record in 2,339 schoolchildren aged 6-14 years in 1998 were compared with the data of 2,108 schoolchildren obtained in 1982. Subjective selfevaluation for signs of health and well-being and smoking and alcohol consumption was estimated in the selected sample of 213 schoolchildren. A questionnaire method was used to evaluate the level of health promotion in schools.
A dísproportion of daily activities has been confirmed in schoolchildren. Currently the differentiatíon in strain associated with education according to the age of children is not accepted. Time, psychical and static strain is highest in the lowest grades, significantly higher in comparison with 1982. The current possibilities of compulsory and private education, ambitions ofparents and weak cooperation between family and school were shown as causes of this situation. On the other hand, the physical and sport activity of the youngest schoolchildren is very low. An unfavorable significant increase of daily television watching and a significant, decrease in sleep time was revealed in each grade. These signs of daily regimen could be reflected in the subjective negative evaluation of health and well-being obtained as well as in risk behavior (smoking, alcohol consumption).
It was revealed that the health care of our schoolchildren is unsatisfactory, caused by the absence of any school health service, formal health education, and poor knowledge of teachers and parents in the area of the promotion of health in schoolchildren.

Atherosclerosis has a multifactorial origin, such as lipid metabolism disorders, hypertension, diabetes mellitus, obesity, as well as behavioural characteristics - cigarette smoking, stress and physical inactivity. These factors represent a high occurrence and cumulation in our population; atherosclerosis is the major cause of death and disability in Slovakia. In the present study some characteristics of health status and life-style in 1,044 career soldiers and civilian employees (men and women) in the Slovak Army were evaluated. Anthropometric data (body mass index, body fat, waist-hip ratio), blood pressure, serum lipids (TC, TG, HDL-C, LDL-C and index of atherogenity TC/HDL-C), some behavioral characteristics (smoking, physical activity, alcohol and drug intake), personal andfamily history and some nutritional habits were estimated.
The results showed a relatively high occurrence of cardiovascular disease risk factors (RF) in a specific population group. The main RF in the youngest group of men were smoking (47.9 %), alcohol intake and experience with drugs. However, the occurrence of RF in older population groups of men was higher (especially being overweight and obese - 59.8 % and worse serum lipids levels). In the group of women there was a lower occurrence of RF and better serum lipid levels (especially high HDL-C levels) in comparison with men. The main negative factors in this group are a high percentage of body fat and low level of physical activity.
The results call for urgent need of early RF identification, the need for timely prevention and especially for intervention programs focused on this specific population subgroup.

We carried out an examination of the health state of fire service personnel in the Hradec Králové District within an extended preventive examination. On the basis of the results we individually recommended a change in life-style (eating regimen, physical activity) and, where it was necessary, we began to treat some disorders (high blood pressure, lipoprotein metabolism disorders, gout). Two years later we repeated the examination and we can compare the results.
In the whole group of examined persons there was an increase in weight, HDL lipoproteins, total protein, the number of erythrocytes and haematocrit two years later. The values of systolic and diastolic blood pressure, resting heart frequency, uric acid level, AST, total cholesterol and thrombocytes decreased. Persons with an increase in physical fitness and/or without an increase in weight showed a more favourable development of anthropometrical, physiological and biochemical parameters during a two-year observation than persons without an increase in fitness and/or with an increase in BMI.

Cleanliness of indoor air is an unthinkable demand in surgical operating rooms - technical equipment only does not guarantee the security of patients and staff. The aim of our study was to investigate the indoor air quality in two operating rooms in a surgical department with difirerent air conditioning. Only one operating room was equipped with fimctioning air conditioning. The air conditioning in the other operating room had not been used for several years because of unsuitable technical parameters. Air samples were taken on flesh-peptone strips using Aeroscop RCS Plus in two operating rooms during surgical procedures. The average number of CFU/m³ in the operating room with air-conditioning'was 1.345 CFU/m³ and in the one without air-conditioning 759.5 CFU/m³. The results ofour measurements were paradoxical atfirst because the results in the operating room without air conditioning were generally better. During our observation of staff activities in the operating room we discovered that movement in the room without air conditioning had been minimal. The operating room with functioning air conditioning and outstanding parameters before the be ginning of surgical day showed a very high movement of stafl and other persons. The door to the operating vestibule and even to the corridor was open. In our study we wanted to mention the fact, that technique, even  unsubstitutable, could not solve the clean indoor air problems and that the human factor and personnel discipline play an important role nowadays.

In our epidemiological study we tried to evaluate the possible health effect of passive smoking on children within the age group of 0-14 years. To estimate the health status and possible external tobacco smoke exposure of children, we asked 1,525 parents to fill in ready made questionnaires. They were asked for their subjective evaluation of child morbidity and information concerning some factors contributing to their children's health status (family history, number of hours spent outdoors, level of physical activity, home pet breeding, living in overcrowded flats, way of heating etc.). Special attention was paid to smoking history. Self reported questionnaire data were then objectivized by checking the health documentation of pediatricians. The number of questionnaires mailed back reached 47%. Our study thus included 711 children, 365 boys and 346 girls. 37% Of respondents came from families who smoked. ln 15% of them mothers were smokers, while in 28% of families fathers smoked. Nevertheless, only 4% of smoking parents admitted to smoking in rooms where children were present. That is maybe why no difference in respiratory disease occurrence between smoking and non-smoking families was found. A detailed analysis nevertheless showed an increased prevalence of lower respiratory tract diseases, their complications and antibiotic treatment in children of younger school age who were from smoking families. The lower correlation between self-reported positive smoking history and respiratory disease frequency can be explained by the fact that only 4% of parents smoked in the presence of their children. There are other factors explaining differences in respiratory disease morbidity (e.g. age Of the children or allergy history Of the parents, namely of mothers).

One of the neglected aspects of military pharmacy historical investigation is the apparatus and furniture equipment necessary for the activity of a military pharmacy. For many centuries the equipment of a military pharmacy depended on the experience of pharmacists who were called up to establish field pharmacies. The establishment of a professional military pharmacy in 1794, however, did not lead to the approval of appropriate standards. In the 19th century the equipment of public, hospital, monastery and military pharmacies was optionally defined by the so-called Ehrman’s standard from 1828-1832. The first lawful standard in the Austro-Hungarian Monarchy defining the equipment ofpharmacies was the Law of December 18, 1906, no. 5 of the Monarchy Law Code of 1907, which established the field of pharmacy. Regulation “Zdrav-1-3 the Pharmaceutical Service in Peacetime“ approved by the Czechoslovak Republic Ministry of National Defence in 1931 became the obligatory standard defining the equipment of military pharmacies. The regulation defined what kind of apparatus, instruments and other equipment military pharmacies had to have in peacetime.

The aim of the work was the comparison of effects of bile acids, mostly used in the therapy, on some parameters of heart activity after their chronical administration. Their possible effects on cardiovascular system are partially known from literature (1,2). Chenodeoxycholic acid (CDCA), ursodeoxycholic acid (UDCA) and deoxycholic acid (DCA) were administered orally once a day in doses 1 g/kg and 0.5 g/kg respectively during 4 weeks. Female rats intoxicated with a dose of isoprenaline 30 mg/kg administered subcutaneously 24 hours before the experiment were used. ECG and blood pressure were measured using Mingograf Siemens-Elema at the beginning and during the experiment, while in 10 minutes intervals mediators of vegetative nervous system were intravenously given. We evaluated R wave height, frequency, PQ, QRS, QT and ST interval lenght and qualitatively ST interval depression or elevation, P wave absence and pathological Q wave occurrence.

Lead (Pb) exerts prooxidative effects and causes oxidative damage to various tissues by altering their antioxidant system. In the experiments male CD rats (Charles River) were treated twice a week with lead acetate at the dose of 12.5 mg/kg body weight ip for 4 weeks with and without Sc co-administration of deferiprone [Lipomed, Switzerland] (LI) at the dose molar ratio to lead acetate 10:1. Pb induced the lipid peroxidation (LPO) in both, the liver and the brain. LI prevented this effect of lead in the liver but not in the brain. L] alone did not change the LPO in liver whereas in the brain an elevation of LPO occured. The level of reduced glutathione (GSH) in the liver was significantly elevated in all groups compared to the control, in the brain increased by L] treatment only. The activity of glutathione peroxidase (GSH-Px) in the liver was not influenced by Pb administration, however the combination of Pb+LI and LI alone decreased the activity of this enzyme. The liver, kidneys, lungs and the brain were analyzed for Pb and essential elements. Pb concentration in the liver, kidneys and brain was not changed by the LI treatment, however Pb level increased in lungs due to L] administration. In the liver and in the kidneys the concentration of most of the essential elements decreased due to Pb-acetate administration and were corrected by L] co-treatment in the liver, however in the kidneys remained unaffected. The level of calcium in the liver was enhanced due to Pb administration and this effect was more expressed by L] co-treatment. In the brain and lungs the changes in essential element concentration were minor.

The influence of isolated soman-induced inhibition of erythrocyte acetylcholinesterase on the basic physiological functions (respiration and circulation) was evaluated in a rabbit model with on-line monitoring of respiratory and circulatory parameters. Following 24h incubation of rabbit erythrocytes with soman (10^-3 M) in vitro, the erythrocytes were added into plasma and injected to intact anaesthetized rabbit. The respiratory and circulatory parameters were monitored till 120 min following the end of blood-transfusion. At the end of experiments, the blood and various organs were removed to measure cholinesterase activities.
No changes in monitored respiratory and circulatory parameters as well as no significant changes in cholinesterase activities with the exception of erythrocyte acetylcholinesterase were observed in comparison with controls. These data suggest that isolated significant decrease in erythrocyte acetylcholinesterase has not any influence on the basic physiological functions in rabbits.

Primary hypertension is the most common chronic disease in industrialized countries. Primary hypertension pathogenesis still remains unclear. However, it is probably a "multifactorial" disease, influenced by various environmetal factors in interaction with a so far undetermined genetic predisposition. A particular diagnosis can only be made through the exclusion of a secondary cause.A small percentage of secondary forms of hypertension in the total population of patients with hypertension justifies us to search for an organically tangible cause of this disease. Any suspicion should correspond with the observance of a standard diagnostic procedure and the appropriate therapy should follow from the expected diagnosis.

Venomous snakes of the Atractaspididae family produce sarafotoxins in their venomous glands which can cause a lethal intoxication in humans by their vasoconstrictive and cardiotoxic effects. Sarafotoxins are peptides and they have structure and pharmacologic properties similar to endothelins. Endothelins are important bioregulators in animals and humans.Recently expressed opinions concerning potential misuse of endothelins as bioterrorism agents are also valid for sarafotoxins. Therefore officials responsible for bioterrorism control ought to pay adequate attention to these substances.

Male NMRI mice were used to test the influence of orally administered prophylactic mean PANPAL on acute toxic effects of tabun and to compare its efficacy with the commonly used pyridostigmine by means of protective ratio evaluation. The effect of antidotal treatment of acute tabun poisoning which depends on the choice of anticholinergic drug or the addition of anticonvulsive drug was compared in the same way. Then the reactivating efficacy of selected oximes was tested on Wistar rats using evaluation of the percentage of tabun-inhibited acetylchollinesterase reactivation in blood, the diaphragm and in the brain of poisoned rats 30 minutes after poisoning and antidotal treatment. We also used the rats to test the influence of pharmacological prophylaxis and the choice of a suitable reactivator for tabun-induced neurotoxic symptoms with the help of functional observatory battery.The results confirm that obidoxime seems to be the most suitable acetylcholinesterase reactivator while the oxime HI-6, which is very effective against soman, is practically ineffective against tabun. Trimedoxim also appears to be a prospective acetylcholinesterase reactivator for the antidotal treatment of tabun poisoning. In order to achieve the sufficient effectiveness of antidotal treatment of acute tabun poisonings, the commonly used anticholinergic drug atropine should be replaced by a cholinolytic drug with pronounced central effects (biperiden, benactyzine, scopolamine). If atropine is used for the antidotal treatment of tabun poisoning, the addition of an anticonvulsive drug such as diazepam is suitable. If PANPAL is administered in case of tabun exposure threat, the resistance of the exposed organism as well as the efficacy of postexposure antidotal treatment are significantly increased. Unlike PANPAL, pyridostigmine is not practically effective against acute toxic effects of tabun.

The author deals with contemporary approaches to active fatigue management and to the stimulation of operational effectiveness of military airmen in combat operations, respectively. The provision of an effective regulation of psychophysiological effectiveness consists of the perfect professional preparedness of flight surgeons in providing this special form of medical care.

The authors point out in their study the basic general risks of biological terrorism. They analyse in detail the nephrotoxicity of mycotoxin ochratoxin A (OTA). The OTA plasmatic level has been examined in a large group of healthy individuals. The OTA levels have been compared in a group of patients with chronic renal insufliciency. A significantly higher OTA level has been proven in patients with chronic renal insuficiency. The possibility of whether OTA retention in chronic renal insuficiency is not an additional accelerating progression factor of basic nephropathy which leads to chronic renal failure has been considered.

This study presents briefly the bystander effect mechanisms in bystander cells and tissues at the genetic and protein level. The possible actions Of overexpressed molecules in bystander cells are explained step by step, i.e. RAD 51, TP 53, CDKNIA (p21, WAF-1), Cyclin B1, p34 (cdc 2), beta 1 integrin, and interleukin 1 alpha actions in bystander mechanisms.

This article briefly Summarizes current knowledge about cyclosporine A, its pharmacokinetic and pharmacodynamíc properties, its effects on organs, tissues, cells as well as its transmembrane transmissions. It also deals with the influence of cyclosporine A on other substances or drugs. Owing to its properties, we can suppose that there will be an increased use of this drug in civilian as well as military medicine than there is at the present time.

Toxicokinetic studies of nerve agents deal with the in vivo absorption, distribution, and elimination of these agents as a function of animal species, route of administration, dose and time after administration. Such studies provide a quantitative basis for toxicodynamic studies of nerve agents, which should result in causal treatment of intoxications with these agents. While toxicodynamic studies of nerve agents have been intensively pursued since WW II, toxicokinetic studies were only initiated in the last two decennia of the twentieth century. The late start of the latter type of research was caused by the long held but uncorrect assumption that nerve agents were so-called “hit-and-run” poisons, with extremely short in vivo persistence. 0n the other hand, such in vivo analyses had to wait for the development, in that period of time, of trace analytical methods which were needed to determine the extremely low (ng to low pg range/ml plasma) but toxicologically significant in vivo levels of the various stereoisomers of nerve agents.
This review will deal first with the development of analytical procedures for chiral trace analysis of the stereoisomers of nerve agents, as well as with the toxicology and routes of in vivo elimination of the stereoisomers. Next, results of toxicokinetic studies will be given, mainly dealing with soman but some results for other nerve agents will also be given. The effect of dose, route of adminstration (iv, inhalation, pc) and animal species will be dealt with, emphasizing the toxicokinetics after low level respiratory exposure. Finally, consequences for prophylactic and therapeutic approaches as well as future directions of research are discussed.

This paper concerns the results of the 12-years prospective scientific and practical researches on the problem of the Long-Term Health Consequences (LTHC) of exposure to dioxins. The results were obtained while solving the tasks of revealing, characterizing and identification of the LTHC of the war chemicals application in Vietnam, and the most prominent of them is “Agent Orange” (AO) — the dioxin—contaminated phytotoxicant used by the US Army during the 2^nd Indochina War [IOM, 1994].