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The effect of morphine withdrawal on G protein-coupled receptors and redox balance in rat brain
Kočárková, Veronika ; Novotný, Jiří (advisor) ; Černá, Barbora (referee)
Although morphine is one of the most effective analgesics available, its long-term use is severely limited by the development of tolerance and dependence. Molecular mechanisms responsible for these effects have been the focus of intensive research for decades aimed at developing safer and more effective pain treatments. The aim of this thesis was to contribute to a better understanding of the molecular actions of morphine, as an understanding of these processes is essential to develop better therapeutic approaches. Using western blot analysis, we investigated the effect of 10-day treatment with increasing doses of morphine and its subsequent withdrawal on key components of opioid signalling in the rat cerebellum and cerebral cortex. Amounts of opioid receptors, various heterotrimeric G protein subunits, GRK3 kinase and β-arrestin 2 were examined. Furthermore, the levels of adenosine A3 receptor and cannabinoid receptor type 1 were detected. Finally, we also investigated the effect of morphine and its withdrawal on oxidative stress markers. Morphine administration resulted in a significant decrease in GRK3 kinase levels in both brain regions, and these changes remained even after withdrawal. However, there was no significant change observed in the content of opioid receptors, different G protein...
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Studies of cell signaling triggered by the TRH receptor
Trubačová, Radka ; Novotný, Jiří (advisor) ; Brejchová, Jana (referee) ; Lazar, Josef (referee)
Activation of thyrotropin-releasing hormone receptor (TRH-R) signaling has an irreplaceable role in a number of cellular processes. Thyroliberin (TRH) plays an important role in the regulation of secretion of other hormones and there are also mentions of its possible antiapoptotic and neuroprotective effects. On the other hand, TRH is quickly degraded and also its other properties, such as cardiac and endocrine side effects and low lipophilicity, disadvantage the therapeutic applications of this hormone compared to its various analogues. Due to their effects on the central nervous systém, TRH and its analogues represent a potential possibility for the treatment of various neurological diseasses, including neurodegenerative disorders. The molecular mechanisms responsible for the beneficial effects of TRH and its analogues have not yet been fully elucidated. So far, little is known about the involvement of TRH, or its analogues, in the regulation of energy metabolism or impact on the cellular phosphoproteome. In the first part of the thesis, we focused on the study of the effect of TRH and interacting partners of TRH-R on the lateral mobility of this receptor in the membrane of the TRY-1 cell line stably expressing TRH-R labeled with yellow fluorescent protein (YFP) at the C-terminus. The results of...
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Rat gut microbiome composition and metabolic faecal markers upon morphine withdrawal
Mičke, Bianka ; Novotný, Jiří (advisor) ; Pácha, Jiří (referee)
The primary purpose of this pilot study was a long-term monitoring of the gut microbiome composition and fecal markers of metabolism in rats following the completion of 10-day intraperitoneal administration of increasing morphine doses (from 10 to 50 mg/kg/day) and in the corresponding control groups of rats that didn't administrate morphine. This study involved the introduction of new methods for microbiome and metabolome research, statistical evaluation of results and interpretation of data, or hypothesis to explain the effects of morphine on the gut microbiome and fecal metabolome composition compared to the resulting data of similarly oriented studies. The actual experiment was conducted on male Wistar rats aged 2 months and weighing approximately 300 g, which were maintained on a standard chow diet. The analysis and evaluation of the resulting data showed that there were changes in the composition of the gut microbiome and fecal metabolome in the experimental group compared to the control group during the reporting period but the induced changes were rather temporary. Further studies should be performed using a significantly larger experimental and control group as well as higher time series granularity. Keywords: morphine, opioids, withdrawal, gut microbiome, faecal metabolome
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Professional Ethics of Public Prosecutors in the Czech Republic
Novotný, Jiří ; Friedel, Tomáš (advisor) ; Chmel, Jan (referee)
Professional ethics of public prosecutors in the Czech Republic Abstract The diploma thesis is dedicated to problematics of professional ethics from its historical concept, conceptual meaning and development, to current perception and practical application in Czech republic, focusing on public prosecutors of Czech republic. Its purpose is to give readers an insight into theoretical basis of the problematics in question and their influence on current practical uses in the light of current legislation, case study, and other relevant sources. The thesis is structured into three chapters arranged in content from the most abstract chapter to the analysis of specific legal institutes and case studies in the last chapter. It therefore proceeds from the general to the specific in terms of the content. The first, theoretical chapter, focuses on the definition of a key concept in this thesis, the ethics, and other related concepts that are included in the thesis, such as morality, responsibility and law. Furthermore, their mutual relations, connections and differences of meaning are also remembered. The second chapter deals with the professional ethics of public prosecutors with regard to their constitutional grounding in the legal order of the Czech Republic and other legal regulation of lower legal force. It also...
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Geometric approach to externally driven quantum systems
Střeleček, Jan ; Cejnar, Pavel (advisor) ; Novotný, Jiří (referee)
The theory of quantum driving of parametric driven Hamiltonians is presented and reformulated using the language of differential geometry. The general fidelity driving in a two-level Hamiltonian system is then analyzed with the particular importance of fidelity time dependence. For the Lipkin-Meshkov-Glick model, the geometrical structure of its energy state manifolds is calculated with an aim to analyze adiabatic and close adiabatic drivings. 1
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Spinor-helicity formalism and amplitudes in different dimensions
Podivín, David ; Kampf, Karol (advisor) ; Novotný, Jiří (referee)
This thesis focuses on spinor-helicity formalism its extensions to different dimensions and its use in constructing scattering amplitudes. At first an outline of this formalism is presented in various dimensions and followed with a brief introduction to constructing amplitudes from a bottom up approach. Following these ideas we calculate possible scattering amplitudes in a theory with a single massless scalar. We further discuss the influence of spacetime dimension on allowed interactions. Lastly we focus on reducing the degrees of freedom in allowed amplitudes by adding properties that interactions should satisfy. These properties are derived from behaviour of known theories. 1
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The role of neuroinflammation in neurodegenerative CNS disease processes
Červenák, Karol ; Novotný, Jiří (advisor) ; Spišská, Veronika (referee)
Inflammatory processes in the CNS are an important element in neuroimmunity. They may be beneficial and have a neuroprotective effect but depending on the extent and duration of their activation they may also have a negative effect on the function of the CNS. Neuroinflammation is characterized by the activation of resident immune cells, microglia and astrocytes, activation of inflammatory signal pathways, recruitment of immune cells from the blood and their penetration through the blood-brain barrier. Chronic neuroinflammation may cause neurodegeneration and is key in the pathogenesis of neurodegenerative diseases. Neurodegeneration is irreversible but it can be mitigated. Therapeutic methods aimed at the modulation of neuroinflammation present a promising option for slowing down or stopping neurodegeneration for people with diseases such as Alzheimer's, Parkinson's, or Huntington's disease. The aim of this thesis is to sum up information about inflammatory processes in the brain and our current knowledge about their role in the pathogenesis of some neurodegenerative diseases. Key words: Inflammation, microglia, neurodegeneration, Alzheimer's disease, Parkinson's disease, Huntington's disease, CNS
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Immunohistochemical analysis of the expression of selected signaling molecules in rat brain: the effect of morphine withdrawal
Přítulová, Eliška ; Novotný, Jiří (advisor) ; Mrózková, Petra (referee)
Morphine is one of the most commonly used analgesics for pain, but its clinical use may be accompanied by the development of tolerance and dependence. Abuse of morphine can then lead to the development of severe withdrawal symptoms. Given the knowledge gathered so far, morphine addiction research often examines the impact on areas of the brain involved in the reward system. The main goal of this work was to investigate the effect of long-term administration of morphine and morphine withdrawal on certain signaling molecules that are related to the molecular action of opioids in selected areas of the rat brain. We focused on the cAMP response element-binding protein (CREB) and its active phosphorylated form (pCREB), as well as on G-protein signaling regulator RGS4. Our results indicated that morphine administration may cause a decrease in CREB expression in the basolateral amygdala in morphine-affected rats. We also found a reduction in CREB phosphorylation in the CA1 region of the hippocampus, possibly due to morphine withdrawal for three months. In this study, we did not observe any statistically significant changes in RGS4 expression in the prefrontal cortex and hippocampus due to morphine administration and subsequent morphine withdrawal. Key words: morphine, dependence, withdrawal, rat brain,...
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Evaluation of Economic Effeciency and Risk of Investment Project
Novotný, Jiří ; Hromádka, Vít (referee) ; Korytárová, Jana (advisor)
The bachelor thesis deals with the evaluation of economic efficiency and risks of an investment project. This is the construction of a multifunctional building in Brno. The theoretical part of the thesis explains the basics concepts, defines the phases of the project life cycle, describes cash flows, economic indicators and deals with project efficiency management. The practical part is devoted to the investment project, especially the creation of cash flows and the resulting evaluation of the economic efficiency of the project. At the end of the work, a sensitivity analysis is demonstrated.
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Communication between PLC S7-1500 and relational database
Novotný, Jiří ; Holek, Radovan (referee) ; Štohl, Radek (advisor)
The thesis deals with the communication methods between the PLC S7-1500 and the database system and it focuses primarily on the possibilities of direct communication, i.e. without the need to use additional software. The thesis presents many of the available solutions, both commercial and freely available. Subsequently, attention is paid to the actual direct communication solution. A solution will be proposed and a~simple application will be implemented demonstrating direct communication between a~Siemens S7-1500 PLC and a Microsoft SQL Server database system. The communication is based on the TDS communication protocol. The implemented application allows direct communication with the database using basic SQL language commands. This solution is competitive with the most currently used indirect communication methods.
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