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Preparation and characterization of surface-modified nanoliposomes using click chemistry techniques
Frydrychová, Aneta ; Bartoš,, Milan (referee) ; Turánek, Jaroslav (advisor)
Over the past decades the liposomes have been intensively studied for their unique properties which predispose them for use as drug delivery systems or for constructions of vaccines. This diploma thesis provides an overview of their most important properties, preparation options and their surface modification. The aim of this thesis is thus a preparation and characterization of the nanoliposomes and their surface modification. The liposomes were prepared by lipid film hydration method and mannan polysacharide was used for surface modification. Due to the use of a lipid with an N-oxy group, the modification was carried out via an oxime ligation via click chemistry. Nanoliposomes were characterized by series of physicochemical methods such as TEM, DLS, FT-IR or nano-flow cytometry. Part of the thesis is a study of the interactions of liposomes accomplished on selected cell lines to verify whether they stimulate immune response pathways. Its results confirmed activation of the NLRP3 inflammasome leading to the production of pro-inflammatory cytokines (IL-1). Thus, these polymer coated nanoliposomes are potentially useful as vaccine adjuvants.
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Preparation and characterization of surface-modified nanoliposomes using click chemistry techniques
Frydrychová, Aneta ; Bartoš,, Milan (referee) ; Turánek, Jaroslav (advisor)
Over the past decades the liposomes have been intensively studied for their unique properties which predispose them for use as drug delivery systems or for constructions of vaccines. This diploma thesis provides an overview of their most important properties, preparation options and their surface modification. The aim of this thesis is thus a preparation and characterization of the nanoliposomes and their surface modification. The liposomes were prepared by lipid film hydration method and mannan polysacharide was used for surface modification. Due to the use of a lipid with an N-oxy group, the modification was carried out via an oxime ligation via click chemistry. Nanoliposomes were characterized by series of physicochemical methods such as TEM, DLS, FT-IR or nano-flow cytometry. Part of the thesis is a study of the interactions of liposomes accomplished on selected cell lines to verify whether they stimulate immune response pathways. Its results confirmed activation of the NLRP3 inflammasome leading to the production of pro-inflammatory cytokines (IL-1). Thus, these polymer coated nanoliposomes are potentially useful as vaccine adjuvants.
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Use of adrenergic receptor alpha2-agonists in pain treatment
Soláriková, Ivana ; Vaculín, Šimon (advisor) ; Maršáková, Lenka (referee)
α2-adrenergic receptor agonists are adjuvant analgesics involved in the modulation and treatment of pain acting in the noradrenergic system. Binding of α2 agonists to receptors initiates a cascade of actions leading i.a. to antinociception. The most clinically applied analgesics of this type include clonidine, dexmedetomidine, and xylazine used in veterinary medicine. The ability to potentiate the effects of opioid and nonopioid analgesics and anesthetics leading to dose reduction is especially advantageous as it relieves unpleasant side effects associated with opioid use, and reduces the risk of tolerance development. They are effective in local anesthesia due to the peripheral site of action and do not cause characteristic, centrally mediated side effects of hemodynamic character. They are involved in the suppression of inflammatory response in the body by inhibiting the production of proinflammatory cytokines. Despite the wide range of action, α2 agonists appear to be safe in many different contraindications, such as sepsis, diabetes or pregnancy. Keywords: α2-adrenergic receptors, agonists, pain, analgesia, clonidine, dexmedetomidine, potentiation, adjuvant
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Immunogenic cell death in tumor specimens in the clinics
Fejfarová, Adéla ; Drbal, Karel (advisor) ; Büchler, Tomáš (referee)
Tumor development and growth are under the control of the immune system in the human body. Danger-associated molecular pattern (DAMP) molecules trigger the anti-tumor response by binding to pattern recognition receptor (PRR) on myeloid cells which in turn activate an adaptive immune system. DAMP molecules are released from cancer cells during a process of immunogenic cell death (ICD) which is a form of regulated cell death (RCD). ICD is induced by a variety of treatments in experimental settings as well as by therapeutic modalities commonly used in medicine. A typical DAMP marker of ICD is calreticulin which is translocated from the endoplasmatic reticulum to the plasma membrane attached to the CD91 receptor. Another marker is the nuclear protein HMGB1 which is released into the tumor environment at the later stage of ICD. This bachelor thesis describes a variety of detection methods and the results of DAMP externalization after ICD induction in vitro in cancer cell lines and in tumor specimens from cancer patiens. Moreover, the link between DAMP molecules and cancer patient survival is discussed. Last, it also summarizes the current status of clinical trials concerning ICD. Keywords tumor, antitumor immunity, cell death, adjuvans, DAMP, chemotherapeutics, immunogenic cell death, clinical trials
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Immunogenic cell death
Šímová, Michaela ; Drbal, Karel (advisor) ; Javorková, Eliška (referee)
According to the danger model, the immune system is activated by endogenous molecules known as danger-associated molecular patterns (DAMP) that are externalized from the interior of a dying cell to the cell surface or released into the extracellular space. Due to the loss of plasma membrane integrity a necrotic cell death as well as several types of proinflammatory programmed cell death are considered to be immunogenic, whereas apoptosis, on contrary, has been initially defined as a tolerogenic type of cell death. However, under certain circumstances, the immune response can be initiated by an apoptotic cell after exnternalization of DAMP molecules by newly described secretory pathways. This phenomenon was observed on tumor cells as a result of some widely used therapeutic modalities and is known as immunogenic cell death (ICD). Nomenclature of selected types of cell death is part of this thesis. The aim of this bachelor thesis is to provide an evidence of the experimental support for ICD theory during in vivo initiation of the immune response. I will evaluate the correlation between ICD and the induced exposure of DAMP molecules on the surface of tumor cells or their secretion to the extracellular space.
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Immunogenic cell death
Šímová, Michaela ; Drbal, Karel (advisor) ; Javorková, Eliška (referee)
According to the danger model, the immune system is activated by endogenous molecules known as danger-associated molecular patterns (DAMP) that are externalized from the interior of a dying cell to the cell surface or released into the extracellular space. Due to the loss of plasma membrane integrity a necrotic cell death as well as several types of proinflammatory programmed cell death are considered to be immunogenic, whereas apoptosis, on contrary, has been initially defined as a tolerogenic type of cell death. However, under certain circumstances, the immune response can be initiated by an apoptotic cell after exnternalization of DAMP molecules by newly described secretory pathways. This phenomenon was observed on tumor cells as a result of some widely used therapeutic modalities and is known as immunogenic cell death (ICD). Nomenclature of selected types of cell death is part of this thesis. The aim of this bachelor thesis is to provide an evidence of the experimental support for ICD theory during in vivo initiation of the immune response. I will evaluate the correlation between ICD and the induced exposure of DAMP molecules on the surface of tumor cells or their secretion to the extracellular space.
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Use of adrenergic receptor alpha2-agonists in pain treatment
Soláriková, Ivana ; Vaculín, Šimon (advisor) ; Maršáková, Lenka (referee)
α2-adrenergic receptor agonists are adjuvant analgesics involved in the modulation and treatment of pain acting in the noradrenergic system. Binding of α2 agonists to receptors initiates a cascade of actions leading i.a. to antinociception. The most clinically applied analgesics of this type include clonidine, dexmedetomidine, and xylazine used in veterinary medicine. The ability to potentiate the effects of opioid and nonopioid analgesics and anesthetics leading to dose reduction is especially advantageous as it relieves unpleasant side effects associated with opioid use, and reduces the risk of tolerance development. They are effective in local anesthesia due to the peripheral site of action and do not cause characteristic, centrally mediated side effects of hemodynamic character. They are involved in the suppression of inflammatory response in the body by inhibiting the production of proinflammatory cytokines. Despite the wide range of action, α2 agonists appear to be safe in many different contraindications, such as sepsis, diabetes or pregnancy. Keywords: α2-adrenergic receptors, agonists, pain, analgesia, clonidine, dexmedetomidine, potentiation, adjuvant
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The behavior of herbicides in kale crop and their impact on the quality of the crop
Kadeřávková, Lenka ; Kočárek, Martin (advisor) ; Břendová, Kateřina (referee)
The thesis is focused on the evaluation of the behavior of herbicides in the growth of kohlrabi. The theoretical and general information on pesticides and herbicides on their behavior in the soil, phytotoxicity (plant injury) and vegetables, are presented in the beginning of the thesis.
A central part deals with the differences in behavior of herbicides in soil with active ingredients metazachlor and pendimethalin, their interaction when applied in a combination and how they behave in the soil when applied separately. It also deals with the results of half-life of applied herbicides. Whether among them was a significant difference in the use of adjuvants, and what kind of effect have the irrigation influenced the experiment. It also evaluates the effect of active substances on the expression of phytotoxicity kohlrabi.
The closing part is focused on the statistical evaluation of the particular options of the applied herbicides. Based on the results the hypothesis has been confirmed. The behavior of the active substances in the soil, which have been applied in the form of mixtures, was differed from the applied herbicides separately. It was found that the applied substance in the mixture have a greater effect on weed control in the crop kohlrabi , longer half-life and their effect on the crop plants is manifested phytotoxic.
The significant impact on the overall evaluation has have the irrigation, which should be an integral part of the application process herbicidal compositions and a follow-up care of a vegetation.
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