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Effect of selected drugs on mitochondrial metabolism in an in vitro model of human skeletal muscle
Krajčová, Adéla ; Anděl, Michal (advisor) ; Kieslichová, Eva (referee) ; Houštěk, Josef (referee)
Introduction: Increasing number of reports reflect that mitochondrial dysfunction can be induced by some of the commonly used drugs and can play a key role in the development of their adverse effects. One of these drugs is a phenol derivative propofol. Propofol is an intravenous, fast and short-acting hypnotic agent, routinely used either for induction and maintenance of anaesthesia during surgery, or for sedation in intensive care units. Propofol infusion syndrome (PRIS) is a rare, but serious adverse effect of the drug with a very high mortality. Typical features of the syndrome include metabolic acidosis, arrhythmias, ECG changes that are similar to those of Brugada syndrome, hypertriglyceridemia, fever, hepatomegaly, rhabdomyolysis, cardiac and/or renal failure. The risk of the syndrome increases with raising dose and duration of propofol administration (˃48 hours). The mechanism of the syndrome is still unknown: pilot studies performed on animal models are suggestive of its mitochondrial origin. In the first part of the study, we performed the analysis of 153 published case reports and all experimental studies related to PRIS. Another aim of the study was to test hypothesis of propofol- induced mitochondrial damage by in vitro exposure of human skeletal muscle-derived cells to a range of...
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Acute kidney injury in critically ill: experimental and clinical approaches
Valešová, Lenka ; Matějovič, Martin (advisor) ; Nalos, Marek (referee) ; Kieslichová, Eva (referee)
Acute kidney injury (AKI) complicates more than one third of intensive care unit admissions and is burdened by high morbidity and mortality of affected patients, with incidence steadily rising. Sepsis is the leading cause of AKI in critically ill. Despite growing insights into the pathogenesis of sepsis- induced AKI, we are so far not able to define successful AKI prevention and treatment. We aimed at assessing molecular mechanisms of sepsis- induced AKI using clinically relevant large animal model of sepsis and implementing new techniques of molecular biology- genomics and proteomics. Although acidosis is a common acid base disorder in critically ill, its role remains controversial. It is unknown whether acidosis is a marker of disease severity or is directly implicated in pathogenesis of acute organ dysfunction states. Its protective role is discussed with growing evidence of acidosis induced cellular energetics downregulation and reduced oxygen demand in stress conditions. We aimed to evaluate physiological effects of different types of acidosis on healthy organism on systemic and regional level, including a complex research of its effects on kidney to search for new AKI preventive and treatment modalities, which permissive acidosis could represent. Key words Acute kidney injury - sepsis -...
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The meaning of the dead donor rule in current transplantion ethics
Rusinová, Kateřina ; Šimek, Jiří (advisor) ; Kieslichová, Eva (referee) ; Hříbek, Tomáš (referee)
The thesis presents current understanding of the concept of death and criteria for diagno- sis of death in the context of organ donation. We will argue that 1) the dead donor rule should not be the necessary condition for retrieving organs for transplantation and 2) it should be permissible to retrieve organs from patients that are imminently dying (not dead yet), with respect to the principle of autonomy and non-maleficence. We will first present the impossibility and current inconsistencies in determining the exact "moment of death" and we will then demonstrate that current organ donors do not fulfill biological criteria for death and that the dead donor rule is not respected in clinical practice. We suggest that in the context of recent major technological advances in the field of critical care medicine the dead donor rule becomes irrelevant and does not contribute to the transplantation ethics. The legal concept of death and the biological phenomenon of death become more and more distant. We argue that declaring death is not necessary for ethically justified policy in transplantation. Both the societal trust and the protection of vulnerable individuals can be ensured by different ethical principles (i.e. the principle of autonomy and the principle of non- maleficence). The sound ethical...
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The influence of the treatment of experimental acute liver failure by FPSA/Prometheus on intracranial pressure
Pražák, Josef ; Cvachovec, Karel (advisor) ; Červinková, Zuzana (referee) ; Kieslichová, Eva (referee)
Background: Cerebral edema is a well-known and fatal complication of acute liver failure (ALF). The influence of the treatment by artificial liver devices on the cerebral damage caused by ALF is usually monitored by only measuring the intracranial pressure (ICP). The aim of this work was to determine the influence of Fractionated Plasma Separation and Adsorption (FPSA), nonbiological artificial liver device, on the intracranial pressure. The second goal of this work was to determine the potential role of cerebral microdialysis in monitoring of the efficiency of fractionated plasma separation and adsorption (FPSA) treatment of ALF. Methods: Two types of surgical resection model of ALF were used in two separate experiments in pigs. In the first study data from monitoring of the intracranial pressure of ALF group (animals with ALF only) and FPSA group (animals with ALF treated by FPSA) were compared. In the second study data from monitoring by cerebral microdialysis and ICP of the ALF group (animals with ALF only), FPSA group (animals with ALF treated by FPSA) and SHAM group (animals with only laparotomy) were compared using statistical analyses. Results: In both experiments, the ICP was significantly higher in the ALF group than in the FPSA group from the 9th hour of the experiment. In the second...
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Transplantation as a treatment for fulminant hepatic failure
Dračka, Pavel ; Mrkvičková, Jaroslava (advisor) ; Kieslichová, Eva (referee)
Předložil jsem případovou studii ošetřovatelské péče u pacienta podstupujícího transplantaci jako léčbu fulminantního selhání jater. V práci popisuji průběh léčby od přijetí nemocného pana B. P. F. na resuscitační oddělení KARIP transplantačního centra IKEM Praha až po překlad na hepatologické oddělení IKEM. Nemocný byl pro akutní jaterní selhání na podkladě intoxikace muchomůrkou zelenou léčen urgentní transplantací jater. V ošetřovatelské části jsem vypracoval ošetřovatelskou anamnézu a podle potřeb nemocného stanovil ošetřovatelské diagnózy k 4. dni hospitalizace/0. den po transplantaci s přehledem realizace a hodnocení všech cílů péče pro zvolený den. Dále se věnuji průběhu hospitalizace, prognóze nemocného a edukaci, kterou dělím na krátkodobou a dlouhodobou. Krátkodobá má charakter edukace sebepéče a dodržování nových hygienických návyků. Plán dlouhodobé edukace vychází ze zcela nové situace pro nemocného po transplantaci orgánu a vlivu této léčby na další život. Velmi důležitou součástí celého ošetřovatelského procesu je vhodná a citlivá forma komunikace s nemocným po transplantaci orgánu.
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