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Role of alarmins in perioperative medicine.
Máca, Jan ; Holub, Michal (advisor) ; Závada, Josef (referee) ; Veselý, Jaroslav (referee)
Introduction: Inflammatory response (IR) is a fundamental reaction to the cell and tissue injury. It is aimed at correcting the pathologic condition and maintaining the structural and functional integrity of the organism. The insult with too extensive or prolonged effect can lead to dysregulation of IR to the systemic level. Major abdominal surgery (MAS) can be considered as a potentially significant insult. Alarmins are endogenous, intracellular proteins that are passively or actively released upon the cell injury to extracellular space where they express their bioactive effect. Alarmins has therefore potential reflect the degree of surgical injury. Purpose: The main goal of the study was elucidating the role of selected alarmins in inflammatory response after MAS. The secondary aims were: 1) determining the relationship between alarmins and outcome prediction, 2) to determine relationship of alarmins and place of surgical intervention, 3) to determine correlation between alarmins and some of the surgery characteristics, e.g. length of surgery, blood loss, and intraoperative fluid load, 4) compare injury caused by laparoscopy and open surgery reflected by alarmins, and 5) to confirm previous results by determining the role of alarmins in surgical injury in subgroup of patients undergoing colorectal...
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Carotenoids of snow algae as biomarkers for exobiology: Raman spectroscopic perspective
Němečková, Kateřina ; Jehlička, Jan (advisor) ; Němec, Ivan (referee)
The major aim of this thesis is critical evaluation of Raman spectroscopy in the detection of carotenoids of extremophiles, namely snow algae. Extremophilic microorganisms play an important role in exobiology since they set hypothetical boundaries for the presence of life on Earth. Raman spectroscopy will be a part of two mission to Mars. Here, a laboratory Raman microspectrometer was used for the analysis of 11 samples of snow algae from different locations over the years 2002-2017. The acquired spectra were compared with HPLC/UV-VIS analysis. The results showed that the ability of Raman spectroscopy to discriminate between structurally slightly differing carotenoid pigments or several carotenoids in an admixture is limited. Contrary, HPLC/UV-VIS permitted to detect various structurally similar carotenoids (and chlorophylls). However, HPLC/UV-VIS worked with overall pigment extracts during which some structural information can be lost. Raman microspectrometer allowed analysis of cells in different life-cycle stages and thus several various spectra could be studied. Raman microspectrometer was therefore more suitable for carotenoid detection in mixtures of various life-stages than HPLC/UV-VIS. Key words carotenoids, snow algae, exobiology, habitability, biomarker, Raman spectroscopy, HPLC/UV-VIS
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The clinical relevance of biomarkers for aggression assessment and prognosis in non-small cell lung cancer
Pražáková, Markéta ; Topolčan, Ondřej (advisor) ; Ludvíková, Marie (referee) ; Molino, Rafael (referee)
Aim: The aim of this thesis was to measure a large spectrum of biomarkers in serum or plasma of patients with operable stage of NSCLC and to evaluate and compare the clinical utility of these biomarkers in the three most important clinical applications for NSCLC: diagnosis, prognosis and postsurgery follow up care. Patients and methods: Total of 22 biomarkers with the most promising profiles were monitored: 8 standard tumor markers (cytokeratines Cyfra 21-1, TPA, TPS, and MonoTotal, CEA, SCC, TK, Chromogranin A) and 14 potential useful biomarkers including pro-inflammatory cytokines IL-6, IL-8, MCP-1, pro-angiogenic cytokine VEGF, matrix metaloproteinases MMP-1, MMP-2, MMP-7, MMP-9 and their inhibitors TIMP-1 and TIMP-2, adhesion molecules ICAM-1, VCAM-1, growth factor IGF-1, and PAI-1 stimulating tumor growth and angiogenesis. With a view of evaluating the clinical relevance of these markers for NSCLC we measured serum or plasma levels of these 22 markers in group of 93 patients with NSCLC undergoing radical surgery and in group of 20 patients with benign lung disease. For biomarker measurement were used conventional immunoanalytic routine methods (IRMA, REA, CLIA, MEIA, TRACE, ELISA) and multiplex immunoanalytic method. Results: Cyfra 21-1, MonoTotal, TPA, TPS, CEA, SCC, Chromogranin A, TIMP-1, MMP-1,...
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Use of biomarkers for the diagnosis and prevention of preeclampsia and eclampsia
Beránková, Hana ; Kovařík, Miroslav (advisor) ; Patková, Anna (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Author: Hana Beránková Supervisor: PharmDr. Miroslav Kovařík, PhD. Title of the bachelor thesis: Use of biomarkers for the diagnosis and prevention of preeclampsia and eclampsia Aim of the thesis: The aim of this thesis was to gain an overview of preeclampsia, to summarize the findings of laboratory examinations for the diagnosis of this disease and to focus on the biochemical markers necessary to recognize the disease. Main findings: Preeclampsia is a hypertensive disease, which today is a major complication of pregnancy. Because of the undetermined etiology, neither the prediction nor the diagnosis of this disease is simple. The levels of some biomarkers, measurable in both blood and urine, make it easier to recognize the approaching disease before the first clinical manifestations. However, there is no factor that would reliably determine whether it is preeclampsia. Therefore, combinations of different markers are currently used. Conclusion: The number of markers shown here proves that it is not easy to define the most reliable ones. Today, physicians choose methods to investigate angiogenic factors and the ratio of soluble fms like tyrosine kinase to placental growth factor...
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Application of Mass Spectrometry for Analysis of Biologically Active and Clinically Significant Compounds.
Štícha, Martin ; Jelínek, Ivan (advisor) ; Smrček, Stanislav (referee) ; Tůma, Petr (referee)
- 8 - ABSTRACT (EN) The thesis is submitted as a commented set of reviewed publications documenting and depicting the possibilities of mass spectrometry in the field of chemical, biological and pharmaceutical research; namely for the purposes of structure elucidation of selected organometallic complexes, analyses of drugs and their metabolites, monitoring of important biological markers. In course of experimental work, the following objectives were studied and solved: Proposal and realization of micro-scale preparation of selected rhenium complexes with aromatic ligands, utilizing tetrabutyammonium tetrachlorooxorhenate as a starting material; preparation and structure characterization of oxorhenium(V) complexes with 1,2-dihydroxybenzene, 1,2,3-trihydroxybenzene, and 2,3- dihydroxynaphtalene as ligands by means of ESI/MS, APPI/MS and LDI-MS; ESI/MS and UV/Vis study of kinetic behavior of complexes arising from the reaction of tetrabutylamonnium tetrachlooxorhenate with pyrogallol and catechol as ligands. Special aim was devoted to the study of subsequent chemical transformation of primarily formed Re(V) complexes; structure characterization of selected ferrocene complexes with copper, gold and silver by means of ESI/MS. Proposal of methodology of structure characterization and quantification of the...
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Novel biomarkers in patients with renal disease
Zakiyanov, Oskar ; Kalousová, Marta (advisor) ; Teplan, Vladimír (referee) ; Průša, Richard (referee)
Chronic kidney disease (CKD) and acute kidney injury (AKI) are major public health problems. It is important to be able to identify those at high risk of adverse outcome, CKD progression and associated cardiovascular disease. The aim of the thesis was to study novel promising biomarkers, their relationship to kidney function, chronic inflammation and/or cardiovascular risk - placental growth factor (PlGF), pregnancy associated plasma protein A (PAPP-A), matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9), soluble receptor for advanced glycation end products (sRAGE), calcium binding protein S100A12 or extracellular newly identified RAGE binding protein (EN-RAGE), and high mobility group box protein-1 (HMGB-1) in patients with renal diseases including CKD, haemodialysis (HD), AKI patients, and healthy controls for comparison. First study revealed that PlGF is elevated in patients with decreased renal function. Second study demonstrated the association of MMP-2 and PAPP-A with proteinuria in patients with CKD. Moreover, serum MMP-2, MMP-9 and PAPP-A levels significantly differed in patients with various nephropathies. EN-RAGE levels are not elevated in patients with CKD, but are related to inflammatory status. PAPP-A, EN-RAGE and HMGB-1 levels are significantly elevated, but sRAGE and PlGF...
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Carbon and Oxygen Stable Isotope Ratio from Foraminiferal Tests as a Key to the Paleoenvironmental Interpretations in the Middle Miocene of the Carpathian Foredeep (Central Paratethys)
Scheiner, Filip ; Holcová, Katarína (advisor) ; Soták, Ján (referee)
The (Lomnice) LOM-1 borehole records a nutrient-rich quiet environment of the outer shelf to upper bathyal in the Mid Badenian (sensu Hohenegger et al. (2014)) of the Carpathian Foredeep. The LOM-1 borehole is rich of a fossil content with a relatively good preservation. The studied section can be correlated with the interval from 14.6 Ma (the FO of Orbulina spp.) to 13.42 Ma (the LO of Sphenolithus heteromorphus) which agrees with the beginning of the "Middle Miocene Climate Transition". The foraminifera for the carbon and oxygen stable isotope analysis were picked from the fraction 0.063-2 mm. The suitability for the stable isotope analysis was carefully evaluated based on the inner wall preservation. The isotopic analysis was done for fifteen samples with total 373 tests analyzed. Each analysis was performed from exactly one test. The following foraminiferal genera from different paleobiotops were used for the isotope analysis: Globigerina bulloides; Orbulina universa, Praeorbulina glomerosa; Globigerinoides spp.; Uvigerina spp.; Heterolepa dutemplei; Cibicidoides spp.; Gyroidinoides spp. and Melonis pompilioides to document the isotopic signal for the superficial and bottom waters. The oxygen and carbon isotope analysis from foraminiferal tests were used for the verification of the...
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Stratification risk of disease progression in patients with abnormal cervical cytologic finding by means of molecular genetic analysis of selected biological factors
Gomolčáková, Barbora ; Kašpírková, Jana (advisor) ; Španielová, Hana (referee)
The aim of this thesis was to track the impact of selected herpesviruses, polyomaviruses, Chlamydia trachomatis and methylation of tumor supressor genes at the development and progression of high grade- lesion in HPV - positive patients by means of molecular-genetic techniques. Confirmation of these markers presence in women with severe lesions of cervix would help to raise necessary specificity of molecular genetics HPV testing and recommend it as a primary screening test for cervical carcinoma prevention. HPV testing could thus replace currently prevailing cytology which has relatively low sensitivity and therefore the number of false negative results. The analyzed samples consisted of cytological cervical smears of 51 HPV positive women, with histologically confirmed presence of severe lesions, collected in liquid medium. Samplings from 51 women without infection were used as a control. The possible effect on disease progress was confirmed only in the case of gene promoters' methylation whose presence was detected in up to 26 patients. It is, however, very unlikely that cancer would develop in all these women. This marker could thus help to stratify patients at risk but only to some extent. Although the individual effect of remaining markers has not been established in the carcinogenesis of cervical...
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The principles of neurosurgical and intensive care liquorology
Kelbich, Petr ; Krejsek, Jan (advisor) ; Krahulík, David (referee) ; Jílek, Petr (referee)
The principles of neurosurgical and neurointensive care liquorology We observed the development of the cerebrospinal fluid (CSF) patterns in 120 patients after bleeding in the CNS (central nervous system). We used our original cytological- energetic principle to investigate 1453 samples of the CSF from these patients. The principal aim of our investigation is the detection of immunocompetitive cells in the CSF and the specification of their activation via the coefficient of energy balance (KEB). Furthermore we evaluated the numbers of erythrocytes and leucocytes in the CSF and also the catalytic activities of the aspartate aminotranspherase (AST) in the CSF as biomarkers of structural disorder of the CNS. Our goal was to evaluate a three week long development of the CSF patterns to gain more accurate information for a more effective therapy and for a better prediction of further clinical development of these patients. We confirmed that following biomarkers were unfavourable for the development of the CSF compartment and probably the CNS as a whole: higher extent of bleeding in the CNS; higher frequency of the neutrophile granulocytes in the CSF compartment; higher extent of anaerobic metabolism in the CSF compartment; higher level of the catalytic activity of the AST in the CSF; higher age...
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