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Changes of internal organs after percutaneous exposure to sulfur mustard
Šulová, Veronika ; Červený, Lukáš (advisor) ; Vokřál, Ivan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Veronika Šulová Supervisor: doc. PharmDr. Lukáš Červený, Ph.D. External supervisor: pplk. doc. MUDr. Jaroslav Pejchal, Ph.D. et Ph.D. Title of diploma thesis: Changes of internal organs after percutaneous exposure to sulfur mustard Sulfur mustard is a chemical warfare agent belonging to the group of blistering agents. The theoretical section of the thesis is mainly focused on the description of acute toxic effects, the mechanism of action, and deals with the current possibilities of poisoning therapy. The experimental section is focused on monitoring the effect of sulfur mustard poisoning in the liver, lung, and kidney of female C57BL/6J mice after the percutaneous administration. This work aimed to evaluate markers of oxidative stress and histopathological changes of the selected organs at 3, 5, and 7 days after the poisoning. Ferric reducing antioxidant power (FRAP) and thiobarbituric acid reactive substances (TBARS) methods were used to determine markers of oxidative stress. Histopathological changes were evaluated microscopically using the hematoxylin-eosin staining method. The airness of the lung parenchyma was also assessed by computer image analysis. First, the LD50 of sulfur mustard was...
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Transport and Deposition of Aerosol in Human Respiratory Tract
Elcner, Jakub ; Kratochvíl, Zdeněk (referee) ; Volavý, Jaroslav (referee) ; Jícha, Miroslav (advisor)
One of approaches in treatment of respiratory system diseases is the use of drug particles suspended in air in the form of aerosol. It is a fast and non-invasive method for the delivery of medicine into tracheobronchial tree or bloodstream. Although the method of the medication dosage by means of inhalers or nebulizers is well known, the effectiveness of that approach is still an actual issue. A significant amount of drugs delivered with the use of the medication dosage never reaches its primary destination and the drugs deposit in antecendent areas of respiratory tract where their presence is not required. This thesis deals with a problem of the passage of monodisperse homogenous aerosol with micron-size particles through the upper parts of the respiratory tract. This work was created with the use of numerical simulations carried out by means of the finite volume method in the commercial code based on computational fluid dynamics. Turbulence was modelled using the Reynolds averaged Navier–Stokes equations with the two-equation eddy viscosity k-omega SST model. The main output of the thesis is the analysis of airflow in two respiratory regimes. Stationary and cyclic cases of the flow behaviour were considered and the validation of simulated results with experiments performed on similar geometries was carried out. Furthermore, the review of simplified lung models and their geometries was made and the acquired results were used for the calculation of air distribution in the respiratory tract. The last part of the thesis deals with the calculation of particle deposition and with the analysis of the results.
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Helminths in the mammalian lungs: migration strategies and pathology
Butula, Dan ; Majer, Martin (advisor) ; Novák, Jan (referee)
This bachelor thesis summarizes the knowledge about the migration strategies of medically important pulmonary helminths and their laboratory models and describes the pulmonary pathology caused by these helminths. Helminths typically enter the lungs within hours or days after infection and often migrate from the lungs to other body organs. Certain species migrate through the lungs intravascularly (schistosome larvae and in certain cases filarial larvae), but others enter the lung parenchyma directly (roundworm larvae, Strongyloides hookworms, adults of Paragonimus flukes, and the metacestode of the tapeworm Echinococcus) or colonise the pleural cavity (adults of Litomosoides sigmodontis and young adults of Paragonimus flukes). This, together with the time spent in the lungs, influences the pathology caused. During this time, mechanical damage to the lung tissue, granuloma formation, infiltration of immune cells, emphysema formation, remodelling of lung tissue and blood vessels, and more can occur. Excretory secretory products of helminths contribute significantly to the pathology, which, among other things, are used as a tool to modulate host immunity and shape the migratory pathway through the lungs. This topic is of particular importance in terms of elucidating the pulmonary processes that are...
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Characterisation and regulation of muscarinic and adrenergic receptors Subtitle: The effect of stress on muscarinic and adrenergic receptors in the lung and in the heart
Nováková, Martina ; Mysliveček, Jaromír (advisor) ; Hynie, Sixtus (referee) ; Mravec, Boris (referee)
The aim of this thesis was to clarify the influence of the stress on the adrenergic and muscarinic receptors in the heart and in the lungs. Research was perform on rat hearts and lungs and on the hearts and lungs of the CRH KO mice. First, we assessed mRNA levels of all α- and β-adrenergic receptor and muscarinic receptor subtypes. Subsequently, we performed the radioligand-binding studies to determine densities of these receptors. We identified all three α1-adrenergic receptor subtypes in the rat lungs. In the lungs of WT mice, we found that the amount of α1-adrenergic and muscarinic receptors was sex-dependent. Densities of the former were higher in females and those of the latter were higher in males. There was no difference between males and females in β-adrenergic receptor density. As for CRH KO mice, the basal densities of studied receptors were lower than in CRH WT mice (except β1-adrenergic receptors in females). The main purpose of the thesis was to detect the immobilization-induced changes in the studied receptors in the kontrol (WT) and CRH KO mice. Short-term and long-term immobilization caused decrease in all α1-adrenergic receptor subtypes in females, whereas only α1A-adrenergic receptors decreased in males. The amount of β1-adrenergic receptors decreased in males and remained without...
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Changes of internal organs after percutaneous exposure to sulfur mustard
Šulová, Veronika ; Červený, Lukáš (advisor) ; Vokřál, Ivan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Veronika Šulová Supervisor: doc. PharmDr. Lukáš Červený, Ph.D. External supervisor: pplk. doc. MUDr. Jaroslav Pejchal, Ph.D. et Ph.D. Title of diploma thesis: Changes of internal organs after percutaneous exposure to sulfur mustard Sulfur mustard is a chemical warfare agent belonging to the group of blistering agents. The theoretical section of the thesis is mainly focused on the description of acute toxic effects, the mechanism of action, and deals with the current possibilities of poisoning therapy. The experimental section is focused on monitoring the effect of sulfur mustard poisoning in the liver, lung, and kidney of female C57BL/6J mice after the percutaneous administration. This work aimed to evaluate markers of oxidative stress and histopathological changes of the selected organs at 3, 5, and 7 days after the poisoning. Ferric reducing antioxidant power (FRAP) and thiobarbituric acid reactive substances (TBARS) methods were used to determine markers of oxidative stress. Histopathological changes were evaluated microscopically using the hematoxylin-eosin staining method. The airness of the lung parenchyma was also assessed by computer image analysis. First, the LD50 of sulfur mustard was...
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Development of mortality from malignant neoplasm of bronchus and lung in the Czech Republic
Hlávko, Petr ; Burcin, Boris (advisor) ; Lustigová, Michala (referee)
Development of mortality from malignant neoplasm of bronchus and lung in the Czech Republic Abstract Malignant neoplasm of bronchus and lung is one of the most common causes of death in the Czech Republic and this diploma thesis aims to evaluate and describe the development of mortality from this disease since the mid-nineties to the present time in the Czech Republic compared to other European countries and on district level. The main goal of this thesis is to analyze the indicators evaluating the structure and intensity of mortality on this common cause of death. The theoretical part describes the selected disease, all the important risk factors, possibilities of prevention, diagnosis, treatment and prognosis of the disease. There are some other theoretical concepts described especially the tobacco epidemic, as smoking is without a doubt the most important risk factor for this disease. Throughout the study period, mortality rates have been converging in the Czech Republic and other selected European countries for malignant neoplasm of bronchus and lung by sex when mortality has decreased significantly for men population, while for women it is slightly increasing. Keywords: mortality, cause of death, malignant neoplasm, bronchus, lung, Czech Republic
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Characterisation and regulation of muscarinic and adrenergic receptors Subtitle: The effect of stress on muscarinic and adrenergic receptors in the lung and in the heart
Nováková, Martina ; Mysliveček, Jaromír (advisor) ; Hynie, Sixtus (referee) ; Mravec, Boris (referee)
The aim of this thesis was to clarify the influence of the stress on the adrenergic and muscarinic receptors in the heart and in the lungs. Research was perform on rat hearts and lungs and on the hearts and lungs of the CRH KO mice. First, we assessed mRNA levels of all α- and β-adrenergic receptor and muscarinic receptor subtypes. Subsequently, we performed the radioligand-binding studies to determine densities of these receptors. We identified all three α1-adrenergic receptor subtypes in the rat lungs. In the lungs of WT mice, we found that the amount of α1-adrenergic and muscarinic receptors was sex-dependent. Densities of the former were higher in females and those of the latter were higher in males. There was no difference between males and females in β-adrenergic receptor density. As for CRH KO mice, the basal densities of studied receptors were lower than in CRH WT mice (except β1-adrenergic receptors in females). The main purpose of the thesis was to detect the immobilization-induced changes in the studied receptors in the kontrol (WT) and CRH KO mice. Short-term and long-term immobilization caused decrease in all α1-adrenergic receptor subtypes in females, whereas only α1A-adrenergic receptors decreased in males. The amount of β1-adrenergic receptors decreased in males and remained without...
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Development of tool for passive immunization of cystic fibrosis patients
Pacholíková, Lenka ; Hodek, Petr (advisor) ; Švédová, Martina (referee)
Cystic Fibrosis (CF) is one of the most common heriditary diseases. This congenital condition, caused by CFTR gene mutation, affects gastrointestinal and respiratory system especially. The affection of respiratory system is considered the most serious life-threatening symptom. Pacients suffer from reccurent infections proceeding to the development of chronic inflammation and progressive pulmonary tissue destruction. A typical specific microoganism colonizating pulmonary tissue of thouse suffering from CF is recognised as Pseudomonas aeruginosa. Pulmonary infections caused by this microorganism are the most often cause of death in patients suffering from CF. Antiobiotics are the first-line therapy of this condition currently. Nevertheless, the need to find alternatives occurs due to antibiotics resistance development. Passive immunization by specific hen-egg-yolk antibodies against P. aeruginosa is a possible alternative. An observation of IgY influence on a bacterial adhesion to pulmonary epithelial cells required an appropriate model. In this context an appropriate adhesion testing method based on P. aeruginosa and pulmonary epithelial cells visualisation was searched. At first bacterial cells labelling was tested by CellTracker, resazurin, FITC and consequently PKH 26. P. aeruginosa fluorescent...
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