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Influence of supplementation with n-3 polyunsaturated fatty acids on inflammatory markers in patients on long-term parenteral nutrition
Svěchová, Hana ; Novák, František (advisor) ; Meisnerová, Eva (referee)
SMOFLipid® is a commonly used fat emulsion for parenteral nutrition. We investigated how enrichment of SMOFLipid® with n-3 polyunsaturated fatty acids (PUFA) in a form of second fat emulsion, Omegaven® , changes fatty acid composition of total plasma phospholipids and erythrocyte phospholipids, cytokine concentrations in serum and in supernatant from in vitro whole blood culture stimulated with lipopolasaccharide (LPS) and we evaluated also changes in oxido- reductive balance. Eight patients on long-term home parenteral nutrition recieved both emulsions, SMOFLipid® (6 weeks) and SMOFLipid® +Omegaven® (4 weeks), one by one. We observed no significant differences in common laboratory and clinical parameters between these two types of diet. Enrichment of SMOFLipid® with Omegaven® led to an increase in eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) in total plasma phospholipids and there was also an increse in proportion of EPA in erythrocyte phospholipids, while proportion of DHA remained unchanged. These changes were in both phospholipids of plasma and erythrocyte compensated for a decrease in proportion of linoleic and arachidonic acid (n-6 PUFA). There were elevated IL-6 and TNF-α serum concentrations in patients after both diets. There was a decrease in IL-6 production by 36% with SMOFLipid®...
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Inflammatory Response after the Implantation of Bioresorbable Vascular Scaffolds vs. 2nd Generation Druh-eluting Stents
Novotný, Vojtěch ; Šťásek, Josef (advisor) ; Kala, Petr (referee) ; Kočka, Viktor (referee)
The concept of bioresorbable scaffolds (BVS) originated in the 90s of the 20th century, however, the first commercially available coronary BVS was Absorb BVS in 2011. The dissertation deals with aspects of working with this type of BVS and its use in real practice. We focused on examining the inflammatory response after implantation of Absorb BVS in comparison with the proven 2nd generation metallic drug eluting stent (DES). The introduction systematically discusses the topic of BVS from history, through the composition of BVS and implantation techniques to available literature data. The second topic discussed is the inflammatory response after coronary stent implantation, we provide an overview of available data from studies and the introduction of inflammatory markers, which were analyzed in the main study. The presented work includes three main studies. A Pilot study in which we evaluated the systemic inflammatory response to coronary artery trauma caused by percutaneous coronary intervention previously described in the literature. We verified that the selected laboratory-determined markers of systemic inflammation (hs-CRP, IL-6 and serum amyloid A) increase significantly 24/48 hours after PCI compared to basal. This pilot study was directly followed by the Randomized study, in which we randomly...
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Intra-amniotic Inflammation in Women with Preterm Labor with Intact Membranes - Clinical and Experimental Aspects
Stráník, Jaroslav ; Kacerovská Musilová, Ivana (advisor) ; Šimetka, Ondřej (referee) ; Čečková, Martina (referee)
Preterm labor with intact membranes (PTL) is responsible for approximately 40% of all preterm deliveries. PTL is frequently complicated by intra-amniotic inflammation (IAI), characterized by the elevation of inflammatory mediators in the amniotic fluid. Based on the presence or absence of microbial invasion of the amniotic cavity (MIAC), two different clinical phenotypes of IAI are distinguished: i) intra-amniotic infection, when microorganisms are present in the amniotic fluid, and ii) sterile IAI, when there are no microorganisms in the amniotic fluid. The clinical severity of both phenotypes of IAI is underlined by their association with adverse neonatal outcomes. In addition to the presence or absence of MIAC, there are also differences between the phenotypes of IAI in terms of their intra-amniotic inflammatory status characteristics. The clinical part of this thesis has addressed these differences in women with PTL. The first specific aim of this clinical study was to determine the concentration of interleukin (IL)-6 in the cervical fluid of women with PTL complicated by intra-amniotic infection and sterile IAI. The second specific aim was to determine the concentration of IgGFc-binding protein (FcgammaBP) in the amniotic and cervical fluids of women with PTL complicated by intra-amniotic...
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The Use of Immune Markers in the Managament of Preterm Birth
Korečko, Vladimír ; Novotný, Zdeněk (advisor) ; Roztočil, Aleš (referee) ; Měchurová, Alena (referee)
Structured summary Aim of the study: To compare the diagnostic reliability, accuracy, and safety of amniocentesis and amniotic fluid Interleukin-6 testing in the diagnosis of intrauterine inflammation of patients with preterm premature rupture of membranes. Type of study: Prospective cohort study Name and location of study site: Department of Gynaecology and Obstetrics, Faculty of Medicine, Charles University in Pilsen Set and methodology: We prospectively examined patients with pPROM between the 23rd and 34th week of gestation in 2014 - 2017. All of them underwent amniocentesis and determination of IL-6 levels in amniotic fluid, leukocytes and bacteria in amniotic fluid as well as maternal blood examination for inflammation parameters. The results were compared to histological examination of the placenta after delivery for the presence of chorioamnionitis. Based on the values mentioned above the sensitivity, specificity, negative and positive predictive value, false positive and negative predictive value and accuracy of the test were determined together with an assessment of statistical significance. Furthermore, the feasibility and incidence of perioperative complications as well as the risk of secondary infection when pregnancy continued were evaluated by serial aniocenteses at weekly intervals. The...
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Sensing of MPyV infection by innate immunity sensors
Rjabčenko, Boris ; Forstová, Jitka (advisor) ; Anděra, Ladislav (referee) ; Mělková, Zora (referee)
Host sensors that recognize pathogen associated molecular patterns and the mechanisms of innate immune response to mouse polyomavirus (MPyV) infection were the main topics of current work. We found that MPyV did not induce interferon (IFN) production during early events of infection, but induced interleukin-6 (IL-6) and other cytokine production without inhibiting virus multiplication. Cytokine microenvironment changed the phenotype of adjacent non infected fibroblasts toward the cancer-associated fibroblast (CAF)-like phenotype. We identified Toll-like receptor 4, a sensor of the innate immunity system, to be responsible for infection dependent IL-6 production. In an effort to determine whether and where virions are released from endosomal compartments into the cytosol, we found that the hydrophobic domains of minor capsid proteins, exposed on the surface of virions after their partial disassembly in the ER, play an important role in effective escape of virions from the lumen part of endoplasmic reticulum into the cytosol, Although naked, partially disassembled virions appear before translocation to the nucleus in the cytosol, viral DNA is not recognized by cytosolic sensors at this phase of infection Sensing of MPyV resulting in IFN production occurs first during viral replication. Mutant virus,...
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Mechanisms of artralgia in targeted therapies for cancer
Mráčková, Monika ; Büchler, Tomáš (advisor) ; Šírová, Milada (referee)
Many targeted anti-tumor therapies result in arthralgia, the non-inflammatory joint pain. The mechanism of pain signaling in arthralgia is not entirely understood but many studies lead to a conclusion that inflammatory cytokines play an important role. Especially interleukin (IL)-6 has been detected in high levels in plasma of patients treated with anti-vascular endothelial growth factor (anti-VEGF) therapy. Although IL-6 seems to be the key factor causing arthralgia, other possible mechanisms have been described. This review focuses on the published data about the correlation between cytokines and cancer-related arthralgia. Possible treatments and future directions are also described.
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Influence of supplementation with n-3 polyunsaturated fatty acids on inflammatory markers in patients on long-term parenteral nutrition
Svěchová, Hana ; Novák, František (advisor) ; Meisnerová, Eva (referee)
SMOFLipid® is a commonly used fat emulsion for parenteral nutrition. We investigated how enrichment of SMOFLipid® with n-3 polyunsaturated fatty acids (PUFA) in a form of second fat emulsion, Omegaven® , changes fatty acid composition of total plasma phospholipids and erythrocyte phospholipids, cytokine concentrations in serum and in supernatant from in vitro whole blood culture stimulated with lipopolasaccharide (LPS) and we evaluated also changes in oxido- reductive balance. Eight patients on long-term home parenteral nutrition recieved both emulsions, SMOFLipid® (6 weeks) and SMOFLipid® +Omegaven® (4 weeks), one by one. We observed no significant differences in common laboratory and clinical parameters between these two types of diet. Enrichment of SMOFLipid® with Omegaven® led to an increase in eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) in total plasma phospholipids and there was also an increse in proportion of EPA in erythrocyte phospholipids, while proportion of DHA remained unchanged. These changes were in both phospholipids of plasma and erythrocyte compensated for a decrease in proportion of linoleic and arachidonic acid (n-6 PUFA). There were elevated IL-6 and TNF-α serum concentrations in patients after both diets. There was a decrease in IL-6 production by 36% with SMOFLipid®...
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