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Identification of new biomarkers and target molecules for the comprehensive treatment (drug-target) via proteomic analysis of body fluids and tissues experimental study
Fremuth, Jiří ; Kobr, Jiří (advisor) ; Nosáľ, Slavomír (referee) ; Hoza, Jozef (referee) ; Slavík, Zdeněk (referee)
The main objective of our prospective experimental study was to develop a clinically relevant model of mechanical ventilation of healthy and damaged lungs ventilated for 12 hours. A widely recommended Vt=6ml/kg was used in comparison with commonly used Vt=10ml/kg. The study included a total of 52 piglets of domestic pig (Sus scrofa f. domestica) age 5-9 weeks. Piglets were divided into 3 groups: group B - Vt = 6ml/kg (11 piglets, 8 died), group C - Vt = 10ml/kg (21 piglets, 5 died) and group D - Vt= 50 ml + instillation of 50 ml saline into the trachea (6 piglets, 1 died). In the presented study we focused on the influence of mechanical ventilation on several organ systems as well as induction of systemic inflammatory reaction. By using higher tidal volume, we aimed to induce possible biotraumatic changes. The ventilator settings were deliberately not changed during the study, except the change of Fi02 values based on the Sp02 value. The first goal was to assess the influence of two different strategies of mechanical ventilation and induced lung injury on respiratory functions of the lungs and pulmonary mechanics. Piglets ventilated with Vt = 6ml/kg maintain the physiological oxemia, but the level of capnia increased over time with an adequate effect on acid-base balance. The highest mortality in...
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The aspiration of gastric contens and the respiratory failure in childhood - the serum and bronchoalveolar lavage proteomic analysis
Hrdlička, René ; Kobr, Jiří (advisor) ; Kopřiva, František (referee) ; Šagát, Tibor (referee)
The aim of the study was the application of new immunoassay procedures in the respiratory failure diagnosis in children based on aspirations. Risk of aspiration, especially in children of the lowest age group, is significantly higher than in those of the other age groups. In some cases, the aspiration may be a fatal incident as sudden infant death syndrome. Currently, there is no exact diagnosis, which would allow to distinguish, when the aspiration is the cause and when it is the result of the respiratory failure. The problem remains also a diagnosis of bacterial contamination during aspiration. This prevents rational deployment of antibiotic treatment. The theoretical part deals with individual biomarkers and their potential contribution to the diagnosis of aspiration. In the current availability of multiplex analysis methodology biomarkers were selected and their dynamics in serum and tracheal aspirate in patients fulfilling the criteria have been analyzed. The biomarkers include cytokines (TNF-α, IL-6, BNP), adhesion molecules (ICAM-1, VCAM- 1, fractalkine) and signal molecules (MMP9 and TIMP1). The group included 15 patients aged under 18 years with lung failure requiring mechanical ventilation based on aspirations. The severity of the clinical condition of the patient was assessed according...
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Multiplex Immunoassay in critically ill children
Šašek, Lumír ; Kobr, Jiří (advisor) ; Kroužecký, Aleš (referee) ; Kula, Roman (referee)
Multiplex immunoassay in critically ill children MUDr. Lumír Šašek Severe lung diseases leading to respiratory failure are the most common causes of critical conditions in childhood. From the perspective of the forecasting is in many cases difficult to identify the further development of the disease and thus allow the setting of adequate therapy. Pulmonary involvement leads to system response, and the response intensity should be at the level of the cytokines directly proportional to the degree of pulmonary disability. This work aims to follow in pediatric patients, the systemic inflammatory response dependence on the degree of lung injury using a multiplex immunoassay on the one hand and clinical, laboratory and imaging parameters on the other. It should identify, if possible, expression of early systemic cytokine markers that correlate with the degree of lung injury, which was determined by standardized scoring and monitoring parameters. This is a prospective, non-randomized observational study. The study group included 32 patients. The study included critically ill patients by PRISM III-12 and LIS with respiratory failure with the need for invasive mechanical ventilation. Patients were followed for up to 48 hours. Correlation between clinical (and laboratory) manifestations of lung disease and...
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Identification of new biomarkers and target molecules for the comprehensive treatment (drug-target) via proteomic analysis of body fluids and tissues experimental study
Fremuth, Jiří ; Kobr, Jiří (advisor) ; Nosáľ, Slavomír (referee) ; Hoza, Jozef (referee) ; Slavík, Zdeněk (referee)
The main objective of our prospective experimental study was to develop a clinically relevant model of mechanical ventilation of healthy and damaged lungs ventilated for 12 hours. A widely recommended Vt=6ml/kg was used in comparison with commonly used Vt=10ml/kg. The study included a total of 52 piglets of domestic pig (Sus scrofa f. domestica) age 5-9 weeks. Piglets were divided into 3 groups: group B - Vt = 6ml/kg (11 piglets, 8 died), group C - Vt = 10ml/kg (21 piglets, 5 died) and group D - Vt= 50 ml + instillation of 50 ml saline into the trachea (6 piglets, 1 died). In the presented study we focused on the influence of mechanical ventilation on several organ systems as well as induction of systemic inflammatory reaction. By using higher tidal volume, we aimed to induce possible biotraumatic changes. The ventilator settings were deliberately not changed during the study, except the change of Fi02 values based on the Sp02 value. The first goal was to assess the influence of two different strategies of mechanical ventilation and induced lung injury on respiratory functions of the lungs and pulmonary mechanics. Piglets ventilated with Vt = 6ml/kg maintain the physiological oxemia, but the level of capnia increased over time with an adequate effect on acid-base balance. The highest mortality in...
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The aspiration of gastric contens and the respiratory failure in childhood - the serum and bronchoalveolar lavage proteomic analysis
Hrdlička, René ; Kobr, Jiří (advisor) ; Kopřiva, František (referee) ; Šagát, Tibor (referee)
The aim of the study was the application of new immunoassay procedures in the respiratory failure diagnosis in children based on aspirations. Risk of aspiration, especially in children of the lowest age group, is significantly higher than in those of the other age groups. In some cases, the aspiration may be a fatal incident as sudden infant death syndrome. Currently, there is no exact diagnosis, which would allow to distinguish, when the aspiration is the cause and when it is the result of the respiratory failure. The problem remains also a diagnosis of bacterial contamination during aspiration. This prevents rational deployment of antibiotic treatment. The theoretical part deals with individual biomarkers and their potential contribution to the diagnosis of aspiration. In the current availability of multiplex analysis methodology biomarkers were selected and their dynamics in serum and tracheal aspirate in patients fulfilling the criteria have been analyzed. The biomarkers include cytokines (TNF-α, IL-6, BNP), adhesion molecules (ICAM-1, VCAM- 1, fractalkine) and signal molecules (MMP9 and TIMP1). The group included 15 patients aged under 18 years with lung failure requiring mechanical ventilation based on aspirations. The severity of the clinical condition of the patient was assessed according...
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Multiplex Immunoassay in critically ill children
Šašek, Lumír ; Kobr, Jiří (advisor) ; Kroužecký, Aleš (referee) ; Kula, Roman (referee)
Multiplex immunoassay in critically ill children MUDr. Lumír Šašek Severe lung diseases leading to respiratory failure are the most common causes of critical conditions in childhood. From the perspective of the forecasting is in many cases difficult to identify the further development of the disease and thus allow the setting of adequate therapy. Pulmonary involvement leads to system response, and the response intensity should be at the level of the cytokines directly proportional to the degree of pulmonary disability. This work aims to follow in pediatric patients, the systemic inflammatory response dependence on the degree of lung injury using a multiplex immunoassay on the one hand and clinical, laboratory and imaging parameters on the other. It should identify, if possible, expression of early systemic cytokine markers that correlate with the degree of lung injury, which was determined by standardized scoring and monitoring parameters. This is a prospective, non-randomized observational study. The study group included 32 patients. The study included critically ill patients by PRISM III-12 and LIS with respiratory failure with the need for invasive mechanical ventilation. Patients were followed for up to 48 hours. Correlation between clinical (and laboratory) manifestations of lung disease and...
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Contribution to the problem of bronchopulmonary dysplasia
Herknerová, Magdalena ; Plavka, Richard (advisor) ; Kobr, Jiří (referee) ; Herget, Jan (referee)
Bronchopulmonary dysplasia (BPD) contributes to significant morbidity of infants with birth weight<1000g. Experimental and clinical research of dissertation thesis has focused on two interventions which might have positive influence on the postnatal development of the immature lung. In animal experiment, we tested the capability of retinoic acid (RA) to attenuate hyperoxic lung injury after seven days exposure to 40% or 80% hyperoxia. RA significantly attenuates the 80% hyperoxic growth retardation. The histological changes were attenuated in the lungs of 40A and 80A groups. The expression of the VEGF-A gene was not significantly influenced by RA in 80% hyperoxia. In another experiment, we detected significant increase of the expression of the gene of proinflammatory cytokine TNF- after 72 hours exposure both to 40% and 80% hyperoxia. Mechanical ventilation still remains one of the risk factors of BPD. The management of optimal lung volume strategy is more difficult during HFOV than conventional ventilation. Efficacy and safety of HFOV is hampered by a lack of reliable bedside in-line monitoring of the patient. We determined the values of expiratory tidal volume measured by hot-wire anemometr and assessed the relationship among VTE and other respiratory parameters. We evaluated how often VTE exceeds the...
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