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The Effect of EGF - like Peptides on Cumulus-Oocyte Complexes
Blaha, Milan ; Němcová, Lucie (advisor) ; Krylov, Vladimír (referee)
In mammals, the ovarian cycle is controlled by follicle-stimulating hormone (FSH) and luteinizing hormone (LH), secreted by the anterior lobe of the pituitary gland. FSH is assumed to be essential for follicle growth. LH is required for the terminal phases of follicle growth, estrogen synthesis, ovulation, development of the corpus luteum and progesterone synthesis. Although cumulus cells and oocytes lack LH-receptors, LH causes cumulus expansion and meiosis resumption. The effect of LH is mediated via EGF-like peptides - amphiregulin (AREG), epiregulin (EREG) and betacellulin (BTC). The precursors of these peptides are present in the mural granulosa cells and EGF-like peptides are released by activation of metalloproteases in response to LH-stimulus. The aim of this thesis is to present EGF-like peptides in the wide context of the molecular mechanisms regulating the late phases of folliculogenesis and meiotic maturation of oocytes.
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The Quality and Safety of Transfusion Products - a Study on Critical Aspects of Quality and Important Factors in Quality Control
Zimová, Renata ; Bláha, Milan (advisor) ; Gašová, Zdenka (referee) ; Turek, Petr (referee)
The quality and safety of transfusion products - a study on critical aspects of quality and important factors in quality control Products made from blood (transfusion products and blood derivatives) represent a special group of therapeutic preparations that have specific properties (danger of allergic reactions, transfer of infections etc.). The aim of this study was to show critical points of the process of producing safe, first-rate transfusion preparations at the level reflecting the progress in medicine and technology. Secondary aim was to analyze whether inspections of the State Institute for Drug Control, strict requirements and implementation of EU legislative have influence on the quality of work in blood establishments (BEs) and whether there are some relations between selected BEs with similar characteristics (the size and type of facility) and quality of work as this is presently a heated topic in discussions about restructuralization of transfusion service. The author analyzed her own experience gained during 129 inspections from the view of Good Manufacturing Practice (GMP) in BEs in the Czech Republic and abroad. The survey of results The most frequent and most important shortcomings (key and critical points) in production of transfusion products are parameters described in the chapter...
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Signaling pathways and genes regulating gonadotropin-induced maturation of porcine oocytes and cumulus expansion
Blaha, Milan ; Němcová, Lucie (advisor) ; Král, Jiří (referee)
In vitro, meotic maturation of porcine oocytes and cumulus expansion are induced by FSH and EGF-like peptides AREG and EREG. FSH and EGF-like peptides induce expression of cumulus expansion-related genes (HAS2, PTGS2 and TNFAIP6). To define signaling pathways that control FSH- and AREG-induced cumulus expansion, porcine cumulus-oocyte complexes were treated with specific protein kinase inhibitors. Inhibitors of MAPK3/1, MAPK14 and ERBB1 significantly reduced both FSH- and AREG-induced expression of HAS2, PTGS2 and TNFAIP6. These inhibitors decreased FSH/LH-induced expression of AREG and EREG in mural granulosa cells. Surprisingly, inhibitor of PKA had no effect on AREG expression in cumulus-oocyte complexes but the inhibitor decreased expression of TNFAIP6 induced by AREG. Inhibitor of PI3K increased expression levels of AREG and PTGS2 but EREG, HAS2 and TNFAIP6 were reduced. Expression levels of the cumulus expansion-related genes were not affected by an analog of cGMP (8-CPT-cGMP). However, 8-CPT-cGMP blocked spontaneous in vitro meiotic maturation of porcine oocytes and its effect was abolished by FSH. Key words: cumulus expansion, cumulus expansion-related genes, meotic maturation, FSH, amphiregulin, cGMP
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Signaling pathways and genes regulating oocyte maturation in pig
Blaha, Milan
The gonadotropin-induced resumption of meiosis and cumulus expansion in preovulatory follicles is preceded by expression of epidermal growth factor (EGF)-like factors, amphiregulin (AREG) and epiregulin (EREG), in mural granulosa and cumulus cells. In vitro, the EGF-like peptides are also produced in cumulus cells upon stimulation by FSH. Both FSH and the EGF-like peptides stimulate resumption of meiosis and cumulus expansion in vitro via activation of a broad signaling network in cumulus cells. To define signaling pathways that drive FSH- and AREG-induced cumulus expansion and meiotic resumption, in vitro cultured pig cumulus-oocyte complexes (COCs) were treated with specific protein kinase inhibitors. The results document that FSH-stimulated, but not the AREG-stimulated resumption of meiosis, depends on the PKA and MAPK14 activities; both modes of stimulation require activation of EGFR and MAPK3/1. To characterize the effects of FSH and EGF-like peptides on gene expression in cumulus cells, transcriptomes of cumulus cells were analysed using microarray approach. Both FSH and AREG+EREG increased the expression of genes associated with regulation of cell proliferation, blood coagulation and extracellular matrix remodeling. In contrast to AREG+EREG, FSH also increased the expression of genes coding...
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Rheohemapheresis (Clinical Importance of Rheological, Technical and Further Hemapheretic Indicators of Effectivity; Side-effects and Economy)
Lánská, Miriam ; Bláha, Milan (advisor) ; Gašová, Zdenka (referee) ; Faber, Edgar (referee)
SUMARY RHEOHEMAPHERESIS - Clinical Importance of Rheological, Technical and Further Hemapheretic Indicators of Effectivity , Side-effects and Economy INTRODUCTION: (Haema)rheopheresis combines the possibilities of haemapheresis (a therapeutic method that is focused on the separation of blood components) and medical rheology (a field of science studying blood fluidity and applying the results of this research to clinical practice in pathological impairments, mainly in the area of microcirculation). The rationale of the effect of rheopheresis (RF): the procedures simultaneously eliminate the exactly defined spectrum of rheologically relevant high-molecular proteins. An immediate pulse reduction of plasma viscosity and viscosity of full blood occurs, which can lead to subsequent permanent "recovery" of the microcirculation with the use of a series of procedures and significantly change the natural course of chronic therapy. RF has been tested in several diseases. This study involves the use of rheopheresis in the dry form of age-related macular degeneration (AMD) and sudden idiopathic sensorineural hearing loss - SISHL. The research was aimed at the optimisation of own modification of rheopheresis, effectivity of procedures, search for the markers of immediate efficacy and prognosis, evaluation of safety and...
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Algorithms for anomaly detection in data from clinical trials and health registries
Bondarenko, Maxim ; Blaha, Milan (referee) ; Schwarz, Daniel (advisor)
This master's thesis deals with the problems of anomalies detection in data from clinical trials and medical registries. The purpose of this work is to perform literary research about quality of data in clinical trials and to design a personal algorithm for detection of anomalous records based on machine learning methods in real clinical data from current or completed clinical trials or medical registries. In the practical part is described the implemented algorithm of detection, consists of several parts: import of data from information system, preprocessing and transformation of imported data records with variables of different data types into numerical vectors, using well known statistical methods for detection outliers and evaluation of the quality and accuracy of the algorithm. The result of creating the algorithm is vector of parameters containing anomalies, which has to make the work of data manager easier. This algorithm is designed for extension the palette of information system functions (CLADE-IS) on automatic monitoring the quality of data by detecting anomalous records.
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Algorithms for anomaly detection in data from clinical trials and health registries
Bondarenko, Maxim ; Blaha, Milan (referee) ; Schwarz, Daniel (advisor)
This master's thesis deals with the problems of anomalies detection in data from clinical trials and medical registries. The purpose of this work is to perform literary research about quality of data in clinical trials and to design a personal algorithm for detection of anomalous records based on machine learning methods in real clinical data from current or completed clinical trials or medical registries. In the practical part is described the implemented algorithm of detection, consists of several parts: import of data from information system, preprocessing and transformation of imported data records with variables of different data types into numerical vectors, using well known statistical methods for detection outliers and evaluation of the quality and accuracy of the algorithm. The result of creating the algorithm is vector of parameters containing anomalies, which has to make the work of data manager easier. This algorithm is designed for extension the palette of information system functions (CLADE-IS) on automatic monitoring the quality of data by detecting anomalous records.
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Signaling pathways and genes regulating oocyte maturation in pig
Blaha, Milan ; Procházka, Radek (advisor) ; Krylov, Vladimír (referee) ; Petr, Jaroslav (referee)
The gonadotropin-induced resumption of meiosis and cumulus expansion in preovulatory follicles is preceded by expression of epidermal growth factor (EGF)-like factors, amphiregulin (AREG) and epiregulin (EREG), in mural granulosa and cumulus cells. In vitro, the EGF-like peptides are also produced in cumulus cells upon stimulation by FSH. Both FSH and the EGF-like peptides stimulate resumption of meiosis and cumulus expansion in vitro via activation of a broad signaling network in cumulus cells. To define signaling pathways that drive FSH- and AREG-induced cumulus expansion and meiotic resumption, in vitro cultured pig cumulus-oocyte complexes (COCs) were treated with specific protein kinase inhibitors. The results document that FSH-stimulated, but not the AREG-stimulated resumption of meiosis, depends on the PKA and MAPK14 activities; both modes of stimulation require activation of EGFR and MAPK3/1. To characterize the effects of FSH and EGF-like peptides on gene expression in cumulus cells, transcriptomes of cumulus cells were analysed using microarray approach. Both FSH and AREG+EREG increased the expression of genes associated with regulation of cell proliferation, blood coagulation and extracellular matrix remodeling. In contrast to AREG+EREG, FSH also increased the expression of genes coding...
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