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Sepsis, septic shock and multiple organ dysfunction syndrome: selected cellular immune mechanisms and methodological aspects
Karvunidis, Thomas ; Matějovič, Martin (advisor) ; Firment, Jozef (referee) ; Průcha, Miroslav (referee)
SEPSIS, SEPTIC SHOCK AND MULTIPLE ORGAN DYSFUNCTION SYNDROME: SELECTED CELLULAR IMMUNE MECHANISMS AND METHODOLOGICAL ASPECTS MUDr. Thomas Karvunidis ABSTRACT Sepsis and septic shock with multiple organ dysfunction syndrome are frequent life-threatening conditions. Despite long-time scientific effort, their exact pathophysiology, causal treatment, and prevention remain obscure. The numbers of mediators and elements (e.g. leukocytes, thrombocytes, endothelium/microcirculation etc.) have been suggested as key mediators in the process of initiation and modulation of this dreadful disease. The aim of the thesis is to better describe and document the cellular mechanisms in the pathophysiology of sepsis, septic shock and multiple organ dysfunction syndrome using different analytic methods including microcirculation assessment, flowcytometry, and proteomics. The first original manuscript studied the role of neutrophils in the process of microcirculation impairment in septic shock patients, as a central pathophysiological mechanism of systemic inflammation. The real-time intravital videomicroscopy technique was used. This is the first clinical study reporting microvascular changes in septic shock patients with chemotherapy-induced cytopenia. The microcirculation injury was identical in cytopenic compared to...
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Sepsis, septic shock and multiple organ dysfunction syndrome: selected cellular immune mechanisms and methodological aspects
Karvunidis, Thomas ; Matějovič, Martin (advisor) ; Firment, Jozef (referee) ; Průcha, Miroslav (referee)
SEPSIS, SEPTIC SHOCK AND MULTIPLE ORGAN DYSFUNCTION SYNDROME: SELECTED CELLULAR IMMUNE MECHANISMS AND METHODOLOGICAL ASPECTS MUDr. Thomas Karvunidis ABSTRACT Sepsis and septic shock with multiple organ dysfunction syndrome are frequent life-threatening conditions. Despite long-time scientific effort, their exact pathophysiology, causal treatment, and prevention remain obscure. The numbers of mediators and elements (e.g. leukocytes, thrombocytes, endothelium/microcirculation etc.) have been suggested as key mediators in the process of initiation and modulation of this dreadful disease. The aim of the thesis is to better describe and document the cellular mechanisms in the pathophysiology of sepsis, septic shock and multiple organ dysfunction syndrome using different analytic methods including microcirculation assessment, flowcytometry, and proteomics. The first original manuscript studied the role of neutrophils in the process of microcirculation impairment in septic shock patients, as a central pathophysiological mechanism of systemic inflammation. The real-time intravital videomicroscopy technique was used. This is the first clinical study reporting microvascular changes in septic shock patients with chemotherapy-induced cytopenia. The microcirculation injury was identical in cytopenic compared to...
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Procalcitonin in critically ill patients
Bureš, Martin ; Průcha, Miroslav (advisor) ; Zazula, Roman (referee)
The aim of this thesis was to determinate the levels of procalcitonin and Creactive protein in the serum of patients who met the criteria of sepsis diagnosis and the comparison with positive blood cultures that is the exact confirmation of infectious etiology of SIRS (Systemic Inflammatory Response Syndrome). Powered by TCPDF (www.tcpdf.org)
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Effect of the pretransplantation conditioning on the effectiveness of bone marrow transplantation in a mouse model
Renešová, Nicol ; Šefc, Luděk (advisor) ; Průcha, Miroslav (referee)
Hematologic malignancies are among the most often diagnosed forms of cancers. Treatment regimens often utilise various combination of cytostatic drugs and total body irradiation and subsequent transplantation of hematopoietic stem cells. One of the most common combinations includes ionising radiation with the antineoplastic alkylating agent cyclophosphamide. In this study we used congenic Ly5.2 and L5.1 mouse strains that express different isoforms of CD45 antigen to evaluate the effects of various time interval between cyclophosphamide and irradiation treatments on the viability of hematopoietic stem cells and their viability. This was done by competitive repopulation assay. The results revealed that level of engraftment and subsequent reconstitution of hematopoiesis can significantly vary and depend on the time interval between cyclophosphamide and total body irradiation administrations. The results indicate that patients with hematologic malignancies could possibly benefit from the treatment especially if they received transplants after being irradiated five or seven days after cyclophosphamide because at that time point their own stem cells would be least competitive. Key words: bone marrow transplantation, cyclophosphamide, chimerism, hematopoietic stem cells, ionising radiation
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Cadaveric bone marrow transplantation: effects of hypoxia and metabolic starvation on mouse hematopoietic stem cells
Linhartová, Jana ; Šefc, Luděk (advisor) ; Průcha, Miroslav (referee) ; Šinkorová, Zuzana (referee)
Objectives: Hematopoietic stem cell transplantation (HSCT) is a widely used method for treatment of hematological disorders and some other diseases. However, sometimes a suitable donor of hematopoietic stem cells (HSC) is not found for a patient. Because HSC have been described as cells with low proliferative and metabolic activity, their tolerance to the lack of oxygen or metabolic substrates may be assumed. In this study, we explored cadaveric bone marrow as an alternative source of HSC for HSCT, using a mouse experimental model. In addition, the effect of in vitro metabolic inhibition and short-term in vitro storage (1 - 4 days) on functional properties of mouse HSC was investigated. Methods: C57Bl/6 mice (wild-type or p53-/- ) were used in the experiments. To explore cadaveric HSC, bone marrow (BM) was left in intact femurs at 37řC, 20řC and 4řC under the conditions of ischemia. The bone marrow cells were harvested after defined time periods ranging 0 - 48 hours. For metabolic inhibition, the electron transport chain inhibitor potassium cyanide (KCN) and inhibitor of glycolysis 2-deoxy-D-glucose (2-DG) were used in vitro. To determine the impact of ischemia, metabolic inhibition, or in vitro storage on transplantability of HSC, the competitive repopulation assay using Ly5.1/Ly5.2 congenic model...
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The Immune response in critically ill patients
Melichová, Jana ; Průcha, Miroslav (advisor) ; Zazula, Roman (referee)
Cardiosurgery is a potent activator of the immune response similar to sepsis in critically ill patients. Therefore the differential diagnostics of infectious and non-infectious etiology plays an important role. The aim of the study was to compare the biomarkers in the diagnostics of patients after cardiosurgery and in septic patients. 24 patients fulfilling criteria of sepsis and 8 patients after cardio surgery were involved in the study. We demonstrated higher specificity and sensitivity of PCT in comparison with CRP at diagnostics of sepsis. sTREM-1, expression of TREM-1 on monocytes, TREM-1 on granulocytes and the number of FoxP3+T regulatory lymphocytes do not provide a reliable differential diagnostics of infectious and non-infectious etiology of examined group of the patients. The number of lymphocytes in patients with sepsis is a useful parameter at this diagnostics. Cardiosurgery represent a significant impulse for the evocation of the systemic inflammatory response of non-infectious etiology.
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NK cells as a corner stone of natural immunity
Melichová, Jana ; Průcha, Miroslav (advisor) ; Čáp, Petr (referee)
Natural killer cells are a subpopulation of T lymphocytes that represents the basal part of cell-mediated immunity. Their main function is to defend the organism against viruses, cancerous cells, microbial- and parasite agents. They act via mediators they produce to influence the other components of innate and adaptive immunity. In the experimental part I deal with the evaluation of changes of NK cells in patients with sepsis. Powered by TCPDF (www.tcpdf.org)
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Immunity in children with cystic fibrosis
Skalická, Anna ; Šedivá, Anna (advisor) ; Průcha, Miroslav (referee)
Cystická fibróza (CF) je závažné autozomálně recesivně dědičné onemocnění způsobené mutací genu CFTR (Cystic Fibrosis Transmembrane Conductance Regulator), který se nachází na dlouhém raménku 7. chromozomu (1). Uváděný výskyt CF je v bělošské populaci jeden případ na 2. 500 narozených dětí. Chorobu způsobují mutace CTFR genu, který ovlivňuje funkci odpovídajícího proteinu a následnou nefunkčnost membránových i iontových kanálů v postižených buňkách. V důsledku poruchy regulace iontového transportu na membránách epiteliálních buněk se mění složení a fyzikálně chemické vlastnosti na povrchu sliznic. Hlenový sekret na povrchu epitelu se zahušťuje a narušená funkce orgánů je příčinou většiny klinických příznaků CF. Onemocnění dýchacích cest a plic je nejzávažnějším projevem CF. Určuje průběh a prognózu a zodpovídá za 90% úmrtí na tuto chorobu. Pacienti s CF trpí chronickými, nejčastěji bakteriálními, respiračními infekcemi. Nejzávažnější jsou infekce způsobené Gram negativními tyčemi Pseudomonas aeruginosa a bakteriemi komplexu Burkholderia cepacia. Eradikace těchto patogenů při chronické infekci prakticky není možná a velká pozornost je věnována mechanismům, které zvyšují patogenicitu těchto mikroorganismů, nicméně uspokojivé vysvětlení chronické perzistence bakteriální infekce právě těmito specifickými...
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