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Hemo elimination method in the treatment of sepsis and early multi-organ dysfunction
Sýkora, Roman ; Matějovič, Martin (advisor) ; Chytra, Ivan (referee) ; Maňák, Jan (referee) ; Šrámek, Vladimír (referee)
The most common cause of death in patients with sepsis/septic shock is deterioration of the function of multiple organs, termed multiple organ dysfunction syndrome. Although our understanding of mechanisms involved in the pathophysiology of sepsis-induced tissue damage has improved substantially, therapy of these syndromes still remains largely supportive. The hallmark of sepsis is an overwhelming systemic production of both pro- and anti-inflammatory mediators leading to generalized endothelial and epithelial damage, microcirculatory-mitochondrial distress, altered endocrine and coagulation homeostasis and cellular immune hyporesponsiveness. Therefore, the hypothesis that modulation of this excessive immunological and biological response to infection might improve patient outcome appears reasonable. Hemoelimination techniques represent biologically plausible way to provide non-specific removal of soluble pro- and anti-inflammatory mediators, although the concept of blood purification in sepsis remains a matter of considerable debate. The aim of this thesis was to elucidate effects of 1) high volume hemofiltration (HVHF) and 2) coupled plasma filtration adsorption (CPFA) in a long-term, hyperdynamic porcine septic shock model, which fulfils the criteria for human sepsis. We hypothesized that both HVHF and...
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Compression of ecaped titanium micro-pillars for two principal orientations
Vokoun, David ; Maňák, Jan ; Tesař, Karel ; Habr, Stanislav
The thermomechanical processing by equal-channel angular pressing (ECAP) is used for certain metals and alloys in order to make their structure fine and to increase material strength. In the previous study done at our institute, grade 2 titanium was successfully processed using four consecutive route A passes via a 90° ECAP die with high backpressure at room temperature. Orientation dependence of compressive and tensile loading of ECAPed titanium samples was demonstrated at macro-scale. However, scarce attention has been paid so far to the mechanical behavior of ECAPed titanium samples at micro-scale. In the present study, compression experiments on titanium micro-pillars, fabricated using focused ion beam, are carried out for two main directions in respect to preceding ECAP pressing (insert and extrusion directions). The purpose of this study is to discuss the orientation dependence of mechanical response during compression of the as-ECAPed titanium micro-pillars.
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ZnMg0.8Ca/Sr0.2 ternary alloys - the influence of the third element on material properties
Čapek, Jaroslav ; Pinc, Jan ; Kubásek, J. ; Molnárová, Orsolya ; Maňák, Jan ; Drahokoupil, Jan
Zinc-based materials alloyed with the elements of the 2nd group of the periodic table have been studied as potential materials for the fabrication of various biodegradable implants. In this study, we prepared two ternary alloys: ZnMg0.8Ca0.2 (wt.%) and ZnMg0.8Sr0.2. The microstructure of both ternary alloys was similar, the main difference was in the size and morphology of the Ca/SrZn13 phase. The SrZn13 phase formed fine particles with a submicron size and had more significant hardening effect in the as-cast state compared to the CaZn13 phase. The annealing led to a transformation of the eutectic structure into the “massive” Mg2Zn11 phase which caused a significant increase of both hardness and compressive yield stress. In the annealed states, comparable hardness was observed for both alloys and higher compressive yield strength for the Ca-containing alloy.
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The Intensive Care Unit-Acquired Weakness: the role of mitochondrial dysfunction in its pathogenesis
Jiroutková, Kateřina ; Duška, František (advisor) ; Houštěk, Josef (referee) ; Maňák, Jan (referee)
BACKGROUND: ICU-acquired weakness impairs functional outcome in survivors of critical illness. Therefore, deepening our understanding of its pathogenesis is an important goal as muscle-specific therapeutic targets are urgently needed. Systemic inflammation and sepsis are the main risk factors of ICUAW, and these syndromes are associated with mitochondrial dysfunction. The aim of our study was to collect reliable information on the mitochondrial function of human skeletal muscle in the protracted phase of critical illness. Additionally, we explored mitochondrial respiratory parameters following experimentally induced changes in the availability or composition of selected nutrients (fatty acids and glutamine). MATERIALS and METHODS: Vastus lateralis muscle biopsy samples from patients with ICU- acquired weakness and age-matched healthy controls were obtained. In human skeletal muscle tissue homogenates mitochondrial functional indices were assessed by high- resolution respirometry, individual functional capacities of respiratory complexes were measured by spectrophotometry and correlated with concentrations of electron transport chain key subunits measured by western blot. Additionally, using human myoblasts and myotubes we studied the influence of extracellular environment manipulations by...
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Acute kidney injury in sepsis: phatophysiological and therapeutical aspects
Chvojka, Jiří ; Matějovič, Martin (advisor) ; Kasal, Eduard (referee) ; Maňák, Jan (referee) ; Balík, Martin (referee)
Sepsis and septic shock remain major cause of mortality in non-coronary intenisve care units. Prognosis of septic patiens worsens further in case of concomitant acute kidney injury. Pathophysiological pathways leading to renal dysfunction in sepsis remain unclear despite of enormous experimental and clinical research. Similarly, the role of extracorporeal blood purification techniques as an adjunctive treatment in sepsis is highly controversial. The aim of our study was to dynamically assess renal haemodynamic, microvascular and metabolic responses in a porcine clinically relevant model of septic shock. The same experimental model was used in experiments elucidating potential benefit effects of two distinct haemopurification methods on different biological responses to infectious insult.
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Disturbances of effective osmolality in acute brain diseases
Špatenková, Věra ; Kazda, Antonín (advisor) ; Maňák, Jan (referee) ; Jabor, Antonín (referee)
Dysbalances of effective osmolality arc some of the most frequent and serious complications in neurointensive care. Their severity lies in brain oedema in hyponatraemia and dehydration of the brain in hypernatraemia. Due to the seriousness of dysnatraemia in acute brain diseases, timely and accurate diagnosis is necessary. Nowadays this is easily achieved through measuring and calculating renal function parameters. The aims of this study were 1) evaluation of hyponatraemia and hypernatraemia in acute brain diseases after establishing these renal parameters into clinical practice in our NNICU and 2) determining the significance ofNT-proBNP in differential diagnostics of hyponatraemia. Over a ten-year period, in a retrospective (1.1.1996 - 31.12.2000) and a prospective study (1.1.2001 - 31.12.2005) we evaluated all patients hospitalised in our NNICU with acute brain diseases, who had scrum sodium below 135 mmol/1 (collection hyponatraemia) or above 150 mmol/1 (collection hypernatraemia). The prospective part took place according to standard protocol for diagnosing hyponatraemia and hypernatraemia in the NNICU, which includes the measuring and calculating of renal function parameters. In the prospective study, assesment of NT-proBNP was carricd out on 40 patients with hyponatraemia. The control group consisted...
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Hemo elimination method in the treatment of sepsis and early multi-organ dysfunction
Sýkora, Roman ; Matějovič, Martin (advisor) ; Chytra, Ivan (referee) ; Maňák, Jan (referee) ; Šrámek, Vladimír (referee)
The most common cause of death in patients with sepsis/septic shock is deterioration of the function of multiple organs, termed multiple organ dysfunction syndrome. Although our understanding of mechanisms involved in the pathophysiology of sepsis-induced tissue damage has improved substantially, therapy of these syndromes still remains largely supportive. The hallmark of sepsis is an overwhelming systemic production of both pro- and anti-inflammatory mediators leading to generalized endothelial and epithelial damage, microcirculatory-mitochondrial distress, altered endocrine and coagulation homeostasis and cellular immune hyporesponsiveness. Therefore, the hypothesis that modulation of this excessive immunological and biological response to infection might improve patient outcome appears reasonable. Hemoelimination techniques represent biologically plausible way to provide non-specific removal of soluble pro- and anti-inflammatory mediators, although the concept of blood purification in sepsis remains a matter of considerable debate. The aim of this thesis was to elucidate effects of 1) high volume hemofiltration (HVHF) and 2) coupled plasma filtration adsorption (CPFA) in a long-term, hyperdynamic porcine septic shock model, which fulfils the criteria for human sepsis. We hypothesized that both HVHF and...
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