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Polymeric particles for targeted anti-inflammatory therapy
Santarius, Karolina ; Holas, Ondřej (advisor) ; Smékalová, Monika (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Mentor: PharmDr. Ondřej Holas, PhD. Consultant: Mgr. Barbora Boltnarová Student: Karolina Santarius Title of thesis: Polymeric particles for targeted anti-inflammatory therapy Macrophages are heterogenous population of cells, that play crucial role in inflammatory diseases like NASH. It was found that liver macrophages polarization into phenotype M1 is major factor in NASH progression. It seems that induced conversion from proinflammatory macrophages into anti-inflammatory is one of the potencial therapeutic target. This macrophages polarization can be achieved by drug delivery system based on drug-loaded nanoparticles. The aim of this work was to prepare and optimize the preparation of nanoparticles formulation based on polymeric nanoparticles loaded dexamethasone as model substance. The nanoparticles formulation was prepared by nanoprecipitation method using three PLGA polymers with different lactic/glycolic acid ratios. Several surfactants in various concentrations were used to optimize preparation. Prepared dexamethasone-loaded nanoparticles were characterized in terms of their size and polydisperzity index using dynamic light scattering. Zeta potencial of nanoparticles was determine by...
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Effect of stress on corticosteroid metabolism in peripheral tissues
Makal, Jakub ; Pácha, Jiří (advisor) ; Vybíral, Stanislav (referee)
Stressor influence can lead to homeostatic disruption. To eliminate this threat, mechanism which compensates negative effects of stressor was evolved by organisms. It's called stress response. One of two major systems that moderate stress response of organism is hypothalamic- pituitary-adrenal axis (HPA axis). Effectors of the HPA axis are glucocorticoids, steroid hormones secreted from adrenal glands. Enzymes which metabolize glucocorticoids are located in target tissues for these hormones. They convert active glucocorticoids into their inactive forms, or vice versa. Untill now, two such enzymes have been described - 11beta-hydroxysteroid dehydrogenases type 1 and type 2. It was proved that expression and activity of these enzymes can change under the influence of stressor. These changes are tissue-specific and dependent on type of applied stressor.
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Effect of stress level on operant conditioning
Lukavská, Markéta ; Nekovářová, Tereza (advisor) ; Santariová, Milena (referee)
Stress is a normal adaptive process and a natural response of the body to those events which are somehow difficult for the individual. It also plays an important part in forming cognitive abilities of animals such as learning. For learning an adequate reaction to the individual's environment it is adaptive to take in as much information as possible, learn to put it into context and react based on it (cognitive strategy). This strategy can help in an ever changing environment as it causes the individual to broaden the range of their behavioural responses and increases the chance of survival. This makes the operant learning a highly desirable method. That is unless the animal finds itself in a situation which calls for a quick response (high level of excitement/agitation) in which case there is no time for processing of information as it is crucial to react instantly (habitual learning - habit strategy). Habitual learning is effective even at a high level of stress when there is "no time" for the operant learning. Operant learning requires the individual's involvement and therefore also the motivation to execute specific behaviour which is then strengthened (in a positive or negative way). In terms of motivation it is a choice between saving energy or safety and the possibility of achieving a...
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Thymectomy and immune mechanisms in patients with myasthenia gravis
Jakubíková, Michala ; Nevšímalová, Soňa (advisor) ; Bojar, Martin (referee) ; Špalek, Peter (referee)
Myasthenia Gravis (MG) is an autoimmune disease affecting neuromuscular transmission, in which the thymus is considered pathogenic organ. Earlier ideas suggesting that MG is only the receptors disease have been proven wrong. There are immunopathological changes in both target structures [specific receptors for acetylcholine (AChR] muscle-specific tyrosine kinase (MuSK) and low-density lipoprotein 4 (Lrp4)], the thymus, as well as in peripheral lymphoid organs. Initial findings of the humoral immunity defect with the decisive role of the pathologic autoantibodies, were corrected with findings of the immune dysregulation at the level of T lymphocytes. According to today's knowledge, the development and maintenance of MG involves almost all cell types of immune function in the autoimmune inflammation: helper CD4+ T lymphocytes, cytotoxic CD8+ T lymphocytes, regulatory CD4+CD25+ T lymphocytes, Th17 lymphocytes, B lymphocytes and plasma cells. Thymus plays a dominant immunopathogenetic role in younger patients with MG, while extrathymic mechanisms are applied in older patients. As a result of that, the thymectomy (TE) is generally accepted as part of treatment for MG. However, there is still no data verified by a prospective controlled study, which would demonstrate a useful result of this treatment...
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Effect of endogenous factors on mesenchymal stem cells
Černá, Kristýna ; Krulová, Magdaléna (advisor) ; Kubinová, Šárka (referee)
Maintaining of homeostasis is essential for the survival of the organism. Stress disturbs the homeostasis and prepares the organism for mental or physical stress. During the stress situation, the endogenous stress factors are released. Through these factors stress affects tissue regeneration, the immune system and other metabolic processes. Chronic stress impacts many parts of body and mind and has a negative effect on these processes. Acute stress has the opposite effect. Mesenchymal stem cells (MSCs) participate in regenerative processes and modulate the immune system. Therefore, it can be assumed that stress will affect on MSCs. The aim of this study was to investigate the effect of stress factors, norepinephrine and corticosterone on the properties and function of MSCs in acute and chronic stress model. In our study, stress factors did not affect the morphology, vitality and differentiation of MSCs. However, the metabolic activity of MSCs was reduced regardless of the duration of their action. The action of stress factors also affected the production of some immunologically relevant molecules and proteins. Unfortunately, the results did not show a clear effect of stress factors on the lymphocyte modulation by MSCs. Key words: mesenchymal stem cells, catecholamines, adrenergic receptors,...
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Thymectomy and immune mechanisms in patients with myasthenia gravis
Jakubíková, Michala ; Nevšímalová, Soňa (advisor) ; Bojar, Martin (referee) ; Špalek, Peter (referee)
Myasthenia Gravis (MG) is an autoimmune disease affecting neuromuscular transmission, in which the thymus is considered pathogenic organ. Earlier ideas suggesting that MG is only the receptors disease have been proven wrong. There are immunopathological changes in both target structures [specific receptors for acetylcholine (AChR] muscle-specific tyrosine kinase (MuSK) and low-density lipoprotein 4 (Lrp4)], the thymus, as well as in peripheral lymphoid organs. Initial findings of the humoral immunity defect with the decisive role of the pathologic autoantibodies, were corrected with findings of the immune dysregulation at the level of T lymphocytes. According to today's knowledge, the development and maintenance of MG involves almost all cell types of immune function in the autoimmune inflammation: helper CD4+ T lymphocytes, cytotoxic CD8+ T lymphocytes, regulatory CD4+CD25+ T lymphocytes, Th17 lymphocytes, B lymphocytes and plasma cells. Thymus plays a dominant immunopathogenetic role in younger patients with MG, while extrathymic mechanisms are applied in older patients. As a result of that, the thymectomy (TE) is generally accepted as part of treatment for MG. However, there is still no data verified by a prospective controlled study, which would demonstrate a useful result of this treatment...
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Effect of stress on corticosteroid metabolism in peripheral tissues
Makal, Jakub ; Pácha, Jiří (advisor) ; Vybíral, Stanislav (referee)
Stressor influence can lead to homeostatic disruption. To eliminate this threat, mechanism which compensates negative effects of stressor was evolved by organisms. It's called stress response. One of two major systems that moderate stress response of organism is hypothalamic- pituitary-adrenal axis (HPA axis). Effectors of the HPA axis are glucocorticoids, steroid hormones secreted from adrenal glands. Enzymes which metabolize glucocorticoids are located in target tissues for these hormones. They convert active glucocorticoids into their inactive forms, or vice versa. Untill now, two such enzymes have been described - 11beta-hydroxysteroid dehydrogenases type 1 and type 2. It was proved that expression and activity of these enzymes can change under the influence of stressor. These changes are tissue-specific and dependent on type of applied stressor.
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