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The effects of total sleep deprivation and ammonia inhalants on the cognitive and physical abilities of military personnel
Maleček, Jan ; Tufano, James Joseph (advisor) ; Conkright, William (referee) ; Kročová, Zuzana (referee)
Given that this dissertation is built up upon three sequential studies, the objectives, methods and results of the thesis are accordingly divided into three distinct subsections (a, b, and c), each corresponding to an individual study. Title: The effects of total sleep deprivation and ammonia inhalants on the cognitive and physical abilities of military personnel Objectives: a) Conducting a literature review to identify the current understanding on the topic and substantial gaps in the literature by investigating the impact of ammonia inhalations on cognitive and physical performance. b) Conducting a methodological study to examine lacking test-retest reliability of standard-issued static and dynamic military shooting protocols for comprehensive investigation of the of total sleep deprivation impact and ammonia inhalants on handgun shooting accuracy. c) Conducting a control trial study to investigate the effectiveness of ammonia inhalants in altering the impact of 36 hours of total sleep deprivation on battery of cognitive and physical performance tests relevant for military personnel. Methods: a) For the purpose of this literature review, a search of the following electronic databases by the author JM was performed: MEDLINE by PubMed, SCOPUS, Web of Science, and Google Scholar. Due to the paucity...
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NK cells and their receptors in immune regulation - possible targets for immunomodulation
Svoboda, Jan ; Fišerová, Anna (advisor) ; Pěknicová, Jana (referee) ; Kročová, Zuzana (referee)
(english) Natural Killers - NK cells play an important role in immune surveilance and regulation either by direct cytotoxicity towards infected, transformed or otherwise damaged cells, or by production of cytokines and chemokines. The resulting response of NK cells is given by the sum of stimulating and inhibiting signals, tranduced by a wide array of receptors. Killer Ig-like receptors KIR2DL4 and LILRB1, which recognize self HLA-G molecules in pregnancy, as well as NKR-P1 receptors, which differ in the number of isotypes, are species-dependent and reduced during phylogenesis. NKG2D, reacting to stress-inducible proteins, and adenosine receptors (AR), which supress the inflamatory reaction, remain evolutionary conserved. The aim of this work was to study the involvement of NK cells and their receptors in several immune disorders and in various species, to provide new insights into their function and posisible immune modulation. We have shown here, that the choice of species in the study of NK cell effector functions may be crucial in some cases. The reaction to glycans, using synthetic GlcNAc-terminated glycomimetics GN8P, exerted opposing effects on NK cell function in humans and C57Bl/6 mice. In humans, the glycomimetic decreased cytotoxic activity of high NKR-P1A expressing NK cells, while in...
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NKR-P1C receptor-carbohydrate interaction contributes to antitumor immune response via activation of NK and B cells
Hulíková, Katarína ; Fišerová, Anna (advisor) ; Kročová, Zuzana (referee) ; Turánek, Jaroslav (referee)
Lectin - saccharide interactions and the involved receptors are currently intensively studied for their important role in antimicrobial as well as antitumor immunity. The major cell types participating in carbohydrate recognition are NK, NKT, and B cells. The differentiation of B lymphocytes could be induced by activated NK cells via direct intercellular contact and/or IFN-γ release. Our research is focused on NK cell receptors of C-type lectin-like family recognizing carbohydrate epitopes of glycoproteins. Synthetic glycoconjugates with terminal N- acetyl-D-glucosamines on polyamidoamine (GN8P) or calix[4]arene (GN4C) scaffold used in this study, exerted the highest binding affinity to activating isoforms of rodent NKR-P1 (A and C) receptor. The aim of the presented dissertation thesis was to elucidate, how Nkr-p1c gene divergence, between C57BL/6 (NK1.1-positive, NKR- P1CB6) and BALB/c (NK1.1-negative, NKR-P1CBALB/c) mouse strains, could affect NK cell activation and subsequent triggering of B lymphocyte effector functions using GN8P and GN4C as NKR-P1C prototype ligands. We demonstrated, that GN8P increased mRNA expression for NKR-P1C receptor, IFN-γ synthesis and lytic activity of NK cells, antigen-specific (anti-KLH, anti-DNP, and anti-B16F10) IgG (particularly IgG2a) formation, number of...
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Inflammatory response induced by cardiac surgery with the use of cardio-pulmonary bypass; the impact of methylprednisolone
Koláčková, Martina ; Krejsek, Jan (advisor) ; Lonský, Vladimír (referee) ; Kročová, Zuzana (referee)
Most elderly people aged over 60 suffer from coronary artery disease (CAD), which can become very likely cause of death. Coronary artery bypass grafting (CABG) represents the standard way of treatment for CAD. CABG surgery is traditionally performed on an arrested heart with the use of cardiopulmonary bypass. The heart is usually accessed through a median sternotomy. Although this kind of surgery strongly stimulates both humoral and cell-mediated immunity, inflammatory response is self-terminating and only a small percentage of patients develop serious postoperative complications, such as organ failure, wound dehiscence, and sepsis. This work focuses on regulatory mechanisms controlling inflammatory response in cardiac surgical patients. It is a retrospective study that follows changes of humoral and cell-mediated immunity induced by cardiac surgery in two different groups of patients. Both groups were operated with the same surgical approach, when identical devices and types of equipment were used; the only difference was the content of 500 mg of methylprednisolone (MP) in priming solution of cardiopulmonary bypass. Blood samples were collected before surgery, after weaning from cardiopulmonary bypass, at the end of surgery, on the 1st , 3rd , and 7th postoperative day. Changes in number of...
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Beating Intracellular Bacterial Infections with Polymeric Nanobead-Based Interventions: Development, Structure Characterization, and Analysis
Trousil, Jiří ; Hrubý, Martin (advisor) ; Záruba, Kamil (referee) ; Kročová, Zuzana (referee)
One hundred years after the discovery of antimicrobials and antibiotics, intracellular bacterial pathogens remain a major cause of global morbidity and mortality. This is due to the complex and intricate ability of these pathogens to undergo intracellular replication while evading host cell immune defense. Bacterial agents such as Legionella pneumophila, Francisella tularensis, and Mycobacterium tuberculosis, as the causative agents of Legionnaires' disease, pulmonary tularemia, and tuberculosis (TB), respectively, contribute to this burden. Moreover, these agents are weaponizable pathogens due to their aerosolizability. TB represents a global health problem, although a potentially curative therapy has been available for approximately 50 years; this intracellular disease affects approximately 1 in 3 people worldwide, with over 10 million new cases per year and one death every three minutes. TB can usually be treated with a 6- to 9-month course of combined therapy. The necessity of using a cocktail of anti-TB drugs and the long-term treatment schedules required for conventional therapy, however, result in poor patient compliance; therefore, the risk of treatment failure and relapses is higher. Hence, improved drug delivery strategies for the existing drugs can be exploited to shorten the duration of TB...
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Molecular Mechanisms of the Interaction of Interacellular Pathogen Francisella Tularensis and Antigen Presenting Cells
Härtlová, Anetta ; Kročová, Zuzana (advisor) ; Černý, Jan (referee) ; Krejsek, Jan (referee)
Title of the PhD thesis: The molecular mechanisms of the interaction of Francisella tularensis and antigen presenting cells Abstract: Over the past few decades, reductionist approaches dominated in the study of biological systems and helped to understand many basic principles that underlie host- pathogen interaction. Nevertheless, recent advances in genomics, transcriptomics and proteomics have enabled to design new type of experiments and get thus novel information of all the components of biological systems, as well as to characterize interaction among them. Profiling of proteins, as main carriers of biological activity, is especially of great interest in order to elucidate the molecular mechanisms of infection in space and time. Nowadays, there is a need to develop new antibiotic and anti-viral drugs, extensively investigate the respective infectious agents in regard to pathogen-specific signaling processes or enzymes that do not occur in human cells. However, pathogens have evolved different strategies to avoid the host defense mechanisms. The fact that pathogens exploit many factors of the host cell signaling machinery for finding safe niche for their replication provides the basis for an alternative, host-directed strategy to prevent establishing of infection in a host. This PhD thesis applies...
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Beating Intracellular Bacterial Infections with Polymeric Nanobead-Based Interventions: Development, Structure Characterization, and Analysis
Trousil, Jiří ; Hrubý, Martin (advisor) ; Záruba, Kamil (referee) ; Kročová, Zuzana (referee)
One hundred years after the discovery of antimicrobials and antibiotics, intracellular bacterial pathogens remain a major cause of global morbidity and mortality. This is due to the complex and intricate ability of these pathogens to undergo intracellular replication while evading host cell immune defense. Bacterial agents such as Legionella pneumophila, Francisella tularensis, and Mycobacterium tuberculosis, as the causative agents of Legionnaires' disease, pulmonary tularemia, and tuberculosis (TB), respectively, contribute to this burden. Moreover, these agents are weaponizable pathogens due to their aerosolizability. TB represents a global health problem, although a potentially curative therapy has been available for approximately 50 years; this intracellular disease affects approximately 1 in 3 people worldwide, with over 10 million new cases per year and one death every three minutes. TB can usually be treated with a 6- to 9-month course of combined therapy. The necessity of using a cocktail of anti-TB drugs and the long-term treatment schedules required for conventional therapy, however, result in poor patient compliance; therefore, the risk of treatment failure and relapses is higher. Hence, improved drug delivery strategies for the existing drugs can be exploited to shorten the duration of TB...
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Inflammatory response induced by cardiac surgery with the use of cardio-pulmonary bypass; the impact of methylprednisolone
Koláčková, Martina ; Krejsek, Jan (advisor) ; Lonský, Vladimír (referee) ; Kročová, Zuzana (referee)
Most elderly people aged over 60 suffer from coronary artery disease (CAD), which can become very likely cause of death. Coronary artery bypass grafting (CABG) represents the standard way of treatment for CAD. CABG surgery is traditionally performed on an arrested heart with the use of cardiopulmonary bypass. The heart is usually accessed through a median sternotomy. Although this kind of surgery strongly stimulates both humoral and cell-mediated immunity, inflammatory response is self-terminating and only a small percentage of patients develop serious postoperative complications, such as organ failure, wound dehiscence, and sepsis. This work focuses on regulatory mechanisms controlling inflammatory response in cardiac surgical patients. It is a retrospective study that follows changes of humoral and cell-mediated immunity induced by cardiac surgery in two different groups of patients. Both groups were operated with the same surgical approach, when identical devices and types of equipment were used; the only difference was the content of 500 mg of methylprednisolone (MP) in priming solution of cardiopulmonary bypass. Blood samples were collected before surgery, after weaning from cardiopulmonary bypass, at the end of surgery, on the 1st , 3rd , and 7th postoperative day. Changes in number of...
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Elements of Immune Fitness
AbuAttieh, Mouhammed O. ; Krejsek, Jan (advisor) ; Raška, Milan (referee) ; Kročová, Zuzana (referee)
1 Charles University in Prague Faculty of Medicine in Hradec Kralove Elements of Immune Fitness Mouhammed O. Abuattieh Abstract of the thesis Doctoral study programme Medical Immunology Hradec Kralove 2013 2 Dissertation thesis was written during combined doctoral study (PhD) study programme Medical Immunology at the Department of Immunology and Allergy, Faculty of Medicine in Hradec Králové, Charles University in Prague and Transplantation Biology Programme, Department of Surgery, Mayo Clinic in Rochester, MN, USA. Author: Mouhammed O. Abuattieh M.D Department of Ophthalmology, Washington University Saint Louis MO, USA. Supervisor: Prof. Jan Krejsek, Ph.D. Chairperson, Department of Immunology and Allergy, Faculty of Medicine in Hradec Králové, Charles University in Prague, Faculty Hospital Hradec Králové, Czech Republic Consultant-Supervisor: Assoc. Prof. Marilia Cascalho M.D., Ph.D. Transplantation Biology Program, University of Michigan, Ann Arbor MI, USA Opponents: Assoc. Prof. Milan Raška, MD., Ph.D. University Palacky, Faculty of Medicine, Institute of Immunology, Olomouc, Czech Republic Assoc. Prof. Zuzana Kročová, Ph.D. University of Defence, Faculty of Military Medicine, Institute of Molecular Pathology Hradec Králové, Czech Republic This thesis will be defended at September 2013 at Department of...
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NK cells and their receptors in immune regulation - possible targets for immunomodulation
Svoboda, Jan ; Fišerová, Anna (advisor) ; Pěknicová, Jana (referee) ; Kročová, Zuzana (referee)
(english) Natural Killers - NK cells play an important role in immune surveilance and regulation either by direct cytotoxicity towards infected, transformed or otherwise damaged cells, or by production of cytokines and chemokines. The resulting response of NK cells is given by the sum of stimulating and inhibiting signals, tranduced by a wide array of receptors. Killer Ig-like receptors KIR2DL4 and LILRB1, which recognize self HLA-G molecules in pregnancy, as well as NKR-P1 receptors, which differ in the number of isotypes, are species-dependent and reduced during phylogenesis. NKG2D, reacting to stress-inducible proteins, and adenosine receptors (AR), which supress the inflamatory reaction, remain evolutionary conserved. The aim of this work was to study the involvement of NK cells and their receptors in several immune disorders and in various species, to provide new insights into their function and posisible immune modulation. We have shown here, that the choice of species in the study of NK cell effector functions may be crucial in some cases. The reaction to glycans, using synthetic GlcNAc-terminated glycomimetics GN8P, exerted opposing effects on NK cell function in humans and C57Bl/6 mice. In humans, the glycomimetic decreased cytotoxic activity of high NKR-P1A expressing NK cells, while in...
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