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Weight Predictor
Kaiserová, Iveta ; Kádě, Ondřej (advisor) ; Šefc, Luděk (referee)
The incidence of obesity is rising worldwide, and one of the major challenges in its treatment is sufficient motivation to persist in the therapeutic process. The factors determining the success of a reduction attempt are also not entirely clear. Therefore, the aim of the "Weight Predictor" project is to develop software that predicts weight change over time in response to lifestyle interventions, and the aim of the thesis was to define the factors influencing weight reduction by testing two hypotheses: "Younger patients reduce their weight more easily than older patients." and "A cooperative patient reduces their weight more easily than a non-cooperative patient." The daily weight, diet, and steps of 29 patients were collected via mobile and web apps, and body composition was measured at regular nutritional consultations. The collected data were processed through exploratory and correlation analysis. Due to insufficient number of records, two patients were excluded from the analysis of daily records and three patients from the analysis of body composition. First hypothesis was not confirmed, while correlation analysis indicated a higher success rate in older patients, which can be explained by the positive correlation found between age and self-monitoring (r = 0.45, significant at p < 0.05). For...
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Cyclophosphamide effects on hematopoiesis
Renešová, Nicol ; Šefc, Luděk (advisor) ; Klevstigová, Martina (referee)
Cyclophosphamide is an alkylating agent developed in the 1960s for the use in treatment of cancerous diseases. Since its introduction, it has manifested various spectra of effects. Of uttermost importance are the impacts cyclophosphamide has on the hematopoietic system housed in the bone marrow of femoral and other bones. Hematopoiesis is a complex process which has been extensively studied for decades. The more it is known about the niches the hematopoietic stem cells occupy as well as of their life cycle, the more it is possible to design functional therapy for its malignancies and improve the survival rates. The effects of cyclophosphamide administration on hematopoietic system are divided into three major cathegories: myeloablation and myelosuppression, immunosuppression, and mobilisation of hematopoietic stem cells into the peripheral blood. The immunosuppression is achieved by systematic depletion of progenitors differentiating into lecocytes. Induced neutropenia and lymphopenia allow for management of autoimmune diseases and preservation of transplants. Mobilisation, a process opposite to stem cell homing, seems to be dependent on disruption of cellular adhesion (CRXCR4/SDF-1, VCAM-1/VLA-4) facilitated by proteases released into the environment after cyclophosphamide exposure.
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Dipeptidyl peptidase IV in orthotopic models of glioma
Hilšer, Marek ; Šedo, Aleksi (advisor) ; Mandys, Václav (referee) ; Šefc, Luděk (referee)
Malignant gliomas belong to a highly aggressive class of tumours. Average patient survival time generally does not exceed 15 months. Despite intensive research, no therapeutic strategies capable of significantly extending the lives of those affected by the disease have been established to date. One potentially viable area of research into possible therapeutic targets in cancer therapy focuses on cell surface proteases. This group of proteins includes dipeptidyl peptidase IV (DPP-IV). Changes to DPP-IV expression have been established in the case of various cancer types including malignant gliomas. Understanding the role of DPP-IV in the biological processes of this malignant disease may thus contribute to the development of new therapeutic modalities. This thesis is therefore dedicated to establishing an orthotopic xenograft model as well as a genetically engineered model (GEM) of the glioma. The effects of DPP-IV on the growth of an experimental glioma were subsequently examined, as was the ratio of catalytic and non- catalytic mechanisms in this process. The GEM model was used for monitoring enzymatic activity and DPP-IV distribution. Non-invasive fluorescence imaging was employed in order to monitor the intraexperimental dynamics of experimental gliomas. The results indicated that DPP-IV...
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Algorithms for multimodal radiography with novel imaging detectors.
Tureček, Daniel ; Šefc, Luděk (advisor) ; Tlustos, Lukas (referee) ; Linhart, Vladimír (referee)
Medical imaging is a technique that allows us to visualize non surgically the internal structure of the human body in order to diagnose or treat medical conditions. It permits also monitoring of physical processes or functions of different organs inside the body. The medical imaging encompasses wide range of techniques based on different physical prin- ciples, including techniques using ionizing radiation. The quality of the images depends significantly on the quality of the used imaging detectors. There are many types of the detectors, from old analog devices (e.g. films) to fully digital detectors such as flat panels, that are the most widely used today. The newer technology is being developed and the techniques such as photon counting explored. However, the state of the art technology is the single photon counting, where the experimental detectors such as Medipix are able to count and process each individual photon. This works studies the properties, features and applications of the newest detector from the Medipix family Timepix3 in different imaging modalities. Firstly, a design of a new hardware readout interface for Timepix3 is presented together with data acquisition software and new analysis and calibration algorithms. Then, different applications of Timepix3 detector were explored: very...
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The cell cycle and differentiation of haematopoietic stem and progenitor cells.
Páral, Petr ; Šefc, Luděk (advisor) ; Horváthová, Monika (referee) ; Kokavec, Juraj (referee)
Haematopoietic stem and progenitor cells (HSPCs) are crucial for lifelong blood cell production. We analysed the cell cycle and cell production rate in HSPCs in murine haematopoiesis. The labelling of DNA-synthesizing cells by two thymidine analogues, optimized for in-vivo use, enabled the determination of the cell cycle flow rate into the G2-phase, the duration of the S-phase and the average cell cycle time in Sca-1+ and Sca-1- HSPCs. The determination of cells with 2n DNA content and labelled during the preceding S-phase was used to establish the cell flow rates in the G1-phase. Our measurements revealed a significant difference in how Sca-1+ and Sca-1- HSPCs self-renew and differentiate. The division of Sca-1+ progenitors led to the loss of the Sca-1 marker in about half of newly produced cells, corresponding to asymmetric cell division. In contrast both Sca-1- progenitors, arising from mitotic cell division, entered a new round of the cell cycle. This corresponds to symmetric self-renewing cell division. The novel data also enabled us to estimate the cell production rates in the Sca-1+ and in three subtypes of Sca-1- HSPCs. We focused on adult murine erythroid differentiation in the next part of our study. We introduced an original flow cytometry approach for identifying and studying erythroid...
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The Role of Patent Foramen Ovale in the Pathophysiology of Decompression Sickness.
Honěk, Jakub ; Šefc, Luděk (advisor) ; Linhartová, Kateřina (referee) ; Mandysová, Eva (referee)
Patent foramen ovale (PFO) has been associated with an increased risk of decompression sickness (DCS) in divers. Pathophysiologicaly this has been ascribed to paradoxical embolization of nitrogen bubbles from venous blood to systemic circulation, resulting in obstruction of peripheral capillaries and ischemic injury. However, the role of PFO has been largely debated and experimental and prospective clinical data has been missing. It is of note, that this hypothesis is not only of theoretical importance. The proof of PFO as a causative factor of DCS and, importantly, of unpredictable events (unprovoked DCS) could affect millions of divers worldwide through improved therapy and prevention. In our research we aimed to describe the pathophysiological role of PFO in decompression sickness and to determine whether the prevention of arterialization of post-dive venous gas emboli (VGE) would decrease the incidence of unprovoked DCS in divers. We have screened 489 scuba divers for the presence of PFO by means of transcranial color-coded Doppler ultrasonography. In a retrospective analysis we found that the incidence of unprovoked decompression sickness was 7% among these divers and that PFO was the only risk factor. Subsequently, we have studied the occurrence of VGE and arterial gas emboli (AGE) in divers with...
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Dipeptidyl peptidase IV in orthotopic models of glioma
Hilšer, Marek ; Šedo, Aleksi (advisor) ; Mandys, Václav (referee) ; Šefc, Luděk (referee)
Malignant gliomas belong to a highly aggressive class of tumours. Average patient survival time generally does not exceed 15 months. Despite intensive research, no therapeutic strategies capable of significantly extending the lives of those affected by the disease have been established to date. One potentially viable area of research into possible therapeutic targets in cancer therapy focuses on cell surface proteases. This group of proteins includes dipeptidyl peptidase IV (DPP-IV). Changes to DPP-IV expression have been established in the case of various cancer types including malignant gliomas. Understanding the role of DPP-IV in the biological processes of this malignant disease may thus contribute to the development of new therapeutic modalities. This thesis is therefore dedicated to establishing an orthotopic xenograft model as well as a genetically engineered model (GEM) of the glioma. The effects of DPP-IV on the growth of an experimental glioma were subsequently examined, as was the ratio of catalytic and non- catalytic mechanisms in this process. The GEM model was used for monitoring enzymatic activity and DPP-IV distribution. Non-invasive fluorescence imaging was employed in order to monitor the intraexperimental dynamics of experimental gliomas. The results indicated that DPP-IV...
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Effect of the pretransplantation conditioning on the effectiveness of bone marrow transplantation in a mouse model
Renešová, Nicol ; Šefc, Luděk (advisor) ; Průcha, Miroslav (referee)
Hematologic malignancies are among the most often diagnosed forms of cancers. Treatment regimens often utilise various combination of cytostatic drugs and total body irradiation and subsequent transplantation of hematopoietic stem cells. One of the most common combinations includes ionising radiation with the antineoplastic alkylating agent cyclophosphamide. In this study we used congenic Ly5.2 and L5.1 mouse strains that express different isoforms of CD45 antigen to evaluate the effects of various time interval between cyclophosphamide and irradiation treatments on the viability of hematopoietic stem cells and their viability. This was done by competitive repopulation assay. The results revealed that level of engraftment and subsequent reconstitution of hematopoiesis can significantly vary and depend on the time interval between cyclophosphamide and total body irradiation administrations. The results indicate that patients with hematologic malignancies could possibly benefit from the treatment especially if they received transplants after being irradiated five or seven days after cyclophosphamide because at that time point their own stem cells would be least competitive. Key words: bone marrow transplantation, cyclophosphamide, chimerism, hematopoietic stem cells, ionising radiation
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Cyclophosphamide effects on hematopoiesis
Renešová, Nicol ; Šefc, Luděk (advisor) ; Klevstigová, Martina (referee)
Cyclophosphamide is an alkylating agent developed in the 1960s for the use in treatment of cancerous diseases. Since its introduction, it has manifested various spectra of effects. Of uttermost importance are the impacts cyclophosphamide has on the hematopoietic system housed in the bone marrow of femoral and other bones. Hematopoiesis is a complex process which has been extensively studied for decades. The more it is known about the niches the hematopoietic stem cells occupy as well as of their life cycle, the more it is possible to design functional therapy for its malignancies and improve the survival rates. The effects of cyclophosphamide administration on hematopoietic system are divided into three major cathegories: myeloablation and myelosuppression, immunosuppression, and mobilisation of hematopoietic stem cells into the peripheral blood. The immunosuppression is achieved by systematic depletion of progenitors differentiating into lecocytes. Induced neutropenia and lymphopenia allow for management of autoimmune diseases and preservation of transplants. Mobilisation, a process opposite to stem cell homing, seems to be dependent on disruption of cellular adhesion (CRXCR4/SDF-1, VCAM-1/VLA-4) facilitated by proteases released into the environment after cyclophosphamide exposure.
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Cadaveric bone marrow transplantation: effects of hypoxia and metabolic starvation on mouse hematopoietic stem cells
Linhartová, Jana ; Šefc, Luděk (advisor) ; Průcha, Miroslav (referee) ; Šinkorová, Zuzana (referee)
Objectives: Hematopoietic stem cell transplantation (HSCT) is a widely used method for treatment of hematological disorders and some other diseases. However, sometimes a suitable donor of hematopoietic stem cells (HSC) is not found for a patient. Because HSC have been described as cells with low proliferative and metabolic activity, their tolerance to the lack of oxygen or metabolic substrates may be assumed. In this study, we explored cadaveric bone marrow as an alternative source of HSC for HSCT, using a mouse experimental model. In addition, the effect of in vitro metabolic inhibition and short-term in vitro storage (1 - 4 days) on functional properties of mouse HSC was investigated. Methods: C57Bl/6 mice (wild-type or p53-/- ) were used in the experiments. To explore cadaveric HSC, bone marrow (BM) was left in intact femurs at 37řC, 20řC and 4řC under the conditions of ischemia. The bone marrow cells were harvested after defined time periods ranging 0 - 48 hours. For metabolic inhibition, the electron transport chain inhibitor potassium cyanide (KCN) and inhibitor of glycolysis 2-deoxy-D-glucose (2-DG) were used in vitro. To determine the impact of ischemia, metabolic inhibition, or in vitro storage on transplantability of HSC, the competitive repopulation assay using Ly5.1/Ly5.2 congenic model...
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