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Pathophysiology of inflammatory bowel disease. Relation to primary scklerosing cholangitis, liver transplantation and carcinogenesis.
Bajer, Lukáš ; Drastich, Pavel (advisor) ; Živný, Jan (referee) ; Procházka, Vlastimil (referee)
Inflammatory bowel disease (IBD) represents a group of multifactorial illnesses with increasing incidence worldwide. Crohn's disease (CD) and ulcerative colitis (UC) are the two most thoroughly defined phenotypes of IBD. IBD associated with primary sclerosing cholangitis (PSC) - a progressive biliary disease leading to cirrhosis and liver failure - is considered as specific IBD phenotype (also referred to as 'PSC - IBD') due to its clinical and pathophysiological characteristics. The aim of the experimental part of this thesis was to define specific features of PSC - IBD in the key areas of IBD pathogenesis. These are: microbiota composition, gut - barrier failure, genetic predisposition and aberrant cellular and antibody immune response. Furthermore, the other goals were to describe relation of IBD status and activity to liver transplantation (LTx) and carcinogenesis based on thorough analysis of clinical data in patients under surveillance at the liver transplantation unit. Using the next-generation parallel sequencing technology, we discovered specific bacterial and mycobial features of gut microbiota composition in PSC - IBD which significantly differed from UC and healthy controls recruited from Czech general population. Moreover, we identified numerous seral biomarkers distinguishing CD, UC...
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Evaluation of incidence and importance of specific organic and functional changes of central nervous system in patients with neurofibromatosis type 1
Glombová, Marie ; Komárek, Vladimír (advisor) ; Nevšímalová, Soňa (referee) ; Starý, Jan (referee)
The aim of the study was to evaluate the importance of brain MRI's findings, and modify the criteria for brain MR imaging in NF1 patients according to this data, to improve the quality of life with early detection of important NF1 complications. Description of the whole cohort, with emphasise to possible cause of high range of sporadic NF1 cases. Evaluation the possibility diagnosis or follow up of brain gliomas by plasmatic values of neuron specific enolase (NSE) and S100B protein. Subjects and methods: I analysed data from 285 NF1 children followed up on our department from 1990 to 2010 by the same examination battery. I evaluated the incidence of brain MRI findings, clinical development, age at gliomas manifestation and necessity of treatment. I also described the whole cohort and made statistic analysis of plasmatic values of NSE and S100B protein in NF1 patients, with and without brain gliomas. Results: OPGs were found in 77/285 (27 %) children and GOOPs in 29/285 (10.2 %) of NF1 children, of who 19 had OPG and GOOP together, so the total number of brain glioma was 87/285 (30.5 %). Totally, 43/87 (49.4 %), respectively 43/285 (15.1 %) children with brain glioma were treated, and 4/285 (1.4 %) of this children died. Obstructive hydrocephalus was found in 22/285 (7.7 %) patients and was caused...
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Risk factors affecting endometriosis in women of reproductive age, ALSWH Study
Olšarová, Karolína ; Dzúrová, Dagmar (advisor) ; Pikhart, Hynek (referee)
This thesis adapts a life course approach in epidemiology to endometriosis. Endometriosis is a highly prevalent chronic disease affecting women in reproductive age. Firstly, the topic of this disease is introduced, the situation and current knowledge in Australia is discussed. Positive changes in a national level are presented. Secondly, early life exposers and maternal behaviour are investigated as possible risk and protective factors. A systematic review of early life factors identified a low birthweight and formula feeding of infants as risk factors for the development of endometriosis. Lastly, the relation of birthweight, weight at childhood and endometriosis was analysed using data of Australian Longitudinal Study on Women's Health. Other risk and protective factors were evaluated and included into the analysis. Logistic regression was used for determination of statistical significance. High weight at 10 years old was found to be a protective factor against endometriosis.
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Using Sperm Transcriptome in Search for Novel Biomarkers of Male Infertility
Semyakina, Anastasiya ; Liška, František (advisor) ; Stopka, Pavel (referee)
Currently infertility affects 10 to 15 percent of couples. In nearly 50% of all cases male factor contributes to infertility of the couple. Majority of causes of male infertility remains unexplained. For this reason, finding simple and clinically useful tools for improving male infertility diagnostics can be important at present. Based on the analysis of sperm transcriptome, in this diploma thesis we aimed to find genes that show differential expression between normal and pathological sperm, this could provide information about molecular basis of male infertility, moreover, expression profile of such genes in sperm could be employed for noninvasive diagnosis of male infertility. This study was conducted by using 67 sperm samples, including 16 control sperm samples from fertile men. The samples of infertile patients were divided into 3 groups according to morphology and motility using results of standard sperm evaluation according to WHO. First group included 20 patients diagnosed with astenoteratozoospermia (low sperm motility and abnormal morphology), second group was 15 patients diagnosed with asthenozoospermia (normal morphology and low sperm motility), the third group comprised 16 samples from infertile patients with normal spermiogram. 16 control samples were from fertile men (conception of...
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Using Sperm Transcriptome in Search for Novel Biomarkers of Male Infertility
Semyakina, Anastasiya ; Liška, František (advisor) ; Stopka, Pavel (referee)
Currently infertility affects 10 to 15 percent of couples. In nearly 50% of all cases male factor contributes to infertility of the couple. Majority of causes of male infertility remains unexplained. For this reason, finding simple and clinically usefµl tools for improving male infertility diagnostics can be important at present. Based on the analysis of sperm transcriptome, in this diploma thesis we aimed to find genes that show differential expression between normal and pathological sperm, this could provide information about molecular basis of male infertility, moreover, expression profile of such genes in sperm could be employed for noninvasive diagnosis of male infertility. This study was conducted by using 67 sperm samples, including 16 control sperm samples from fertile men. The samples of infertile patients were divided into 3 groups according to morphology and motility using results of standard sperm evaluation according to WHO. First group included 20 patients diagnosed with astenoteratozoospermia (low sperm motility and abnormal morphology), second group was 15 patients diagnosed with asthenozoospermia (normal morphology and low sperm motility), the third group comprised 16 samples from infertile patients with normal spermiogram. 16 control samples were from fertile men (conception of...
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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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