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Acromegaly in patients with somatotroph pituitary adenomas - determining the expression level of proteins with а potential influence on the therapeutic response
Krbalová, Lenka ; Macháček, Miloslav (advisor) ; Pejchal, Jaroslav (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: RNDr. Mgr. Lenka Krbalová Supervisor: RNDr. Miloslav Macháček, Ph.D. Consultant Supervisor: MUDr. Jiří Soukup, Ph.D. Title of the rigorous thesis: Acromegaly in patients with somatotroph pituitary adenomas - determining the expression level of proteins with a potential influence on the therapeutic response Acromegaly is a rare disease manifested by a wide variety of symptoms (enlargement of the acral parts of the body, macroglossia, neuropathy, hypertension, cardiomyopathy etc.). These symptoms significantly decrease quality of life and shorten life span. It is caused by increased secretion of growth hormone in adulthood. The cause of this increased secretion is most often a somatotroph adenoma. In most cases, the treatment of acromegaly requires a comprehensive approach. It is a combination of surgical intervention, radiotherapy and pharmacotherapy. Somatostatin analogues are mainly used in pharmacotherapy. These compounds have similar pharmacodynamic effects as somatostatin after binding to the somatostatin receptor. The administration of these compounds leads to a decrease in the secretory activity of the tumour and subsequently to the reduction of its volume. Octreotide and lanreotide belong...
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Study of novel phthalocyanine photosensitizers on cellular level
Halašková, Marie ; Macháček, Miloslav (advisor) ; Pejchal, Jaroslav (referee) ; Hofman, Jakub (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Mgr. Marie Halašková Supervisor: RNDr. Miloslav Macháček, Ph.D. Title of disertation thesis: Study of novel phthalocyanine photosensitizers on cellular level Photodynamic therapy (PDT) is a clinically approved treatment modality that experienced great progress over the last two decades and that has been used in the treatment of several disorders, including age-related macular degeneration, psoriasis and certain cancers. PDT is based on the combination of three main components: light-sensitive drug (known as a photosensitizer, PS), light of an appropriate wavelength, and oxygen. The light-activated PS reacts with molecular oxygen to produce reactive oxygen species, which can interact with cellular components in a biological environment and trigger a cascade of reactions causing destruction of tumor cells, tumor vasculature and induction of a local inflammatory reaction. The result is a disruption of cell homeostasis leading to the cell death. Like all the novel treatment modalities, further research is still needed including the development and optimization of PS synthesis in order to increase the efficiency of therapy and minimalize side effects. In this project, we decided to carry out an...
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Study of Anticancer Effect of New Low-molecular-weight PIKK Inhibitors
Kulhavá, Monika ; Řezáčová, Martina (advisor) ; Pejchal, Jaroslav (referee) ; Vinklárek, Jaromír (referee)
Conventional radiotherapy and chemotherapy interfere with the basic functions of dividing cells and are very effective againts rapidly proliferating tumor cells. They are still an indispensable tool in the fight against cancer, but their interventions also affect healthy cells and cause a number of side effects. Due to the instability of the gemone of tumor cells and frequent mutations, increased aggressiveness and resistence to treatment can occur. Tumor resistence to treatment is a very serious problem. There are a number of mechanisms by which cells defend themselves. One of the fundamental causes of resistence is the natural ability of all cells to repair damaged DNA. On the one hand, this is indispensable for cell life. On the other hand, it reduces the effect of chemotherapy or radiotherapy, which are based on the principle of causing DNA lesions. Small interventions in the signaling pathways of the cell's repair system can contribute to increasing the effectiveness of cytotoxic treatment. DNA-PK is serine/threonine kinase that is activated by DNA double-strand breaks which are considered the most lethal type of damage caused by radiation and some chemotherapy drugs. Activation of this kinase triggers signaling cascades that can lead to DNA repair, cell cycle arrest, or apoptosis. By...
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Study of the effectiveness of the original amphiphilic (aza)phthalocyanines bearing permanent positive charge
Rohlíčková, Monika ; Macháček, Miloslav (advisor) ; Pejchal, Jaroslav (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Monika Steklá Supervisor: RNDr. Miloslav Macháček, Ph.D. Title of diploma thesis: Study of the effectiveness of the original amphiphilic (aza)phthalocyanines bearing permanent positive charge The neoplastic diseases are nowadays one of the most common reason of death in developed countries. That is the reason why is a great attention dedicated to the development of new methods for the treatment these diseases. One of such modern methods is the photodynamic therapy. This is a very selective, minimally invasive method with a minimum of side effects. The principle of this type of therapy is application of separately inactive compound, called photosensitizer, followed by exposure to light with suitable wavelength in the presence of molecular oxygen. Therefore, the photodynamic therapy needs three basic components: the photosensitizer, light and oxygen. Each of those components are non-toxic, when they occur separately. However, their combination lead to the inception of the photochemical reaction in which are generated reactive oxygen species, especially singlet oxygen. These very reactive molecules damage target cells, which subsequently die via apoptosis or necrosis. As has been said, the main...
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A study on the activity of α-tomatine and newly synthetized derivatives of benzo[c]fluorene
Suchá, Lenka ; Tomšík, Pavel (advisor) ; Pejchal, Jaroslav (referee) ; Poučková, Pavla (referee)
Many of anticancer drugs are of natural origin. Plants from the Solanaceae family contain various steroidal glycoalkaloids that are toxic to cancer cells. The aim of the first part of this work was to evaluate the potential anticancer effect of α-tomatine - a steroidal glycoalkaloid from Solanaceae plant family. The second part of this work was focused on the anticancer research of newly synthetized derivatives of benzo[c]fluorene. Benfluron, one of the derivatives, was reported 30 years ago to have anticancer effects in vitro and in vivo almost. Tomatine inhibited the proliferation and viability of MCF-7 cells. In this cancer cell line treated with tomatine, no DNA damage, no changes in p53 and p21WAF1/CIP1 protein levels, neither the induction of apoptosis was demonstrated. However, the decrease in ATP levels was found. New synthetized derivatives of benfluron and dimefluron caused higher cytotoxic effect in the different cancer cell lines compared with their original compounds. On the other hand, these derivatives did not caused higher tumour growth inhibition when compared with their original compounds in in vivo studies. Benfluron and hydrazone of dimeflurone prolonged the survival of mice with inoculated solid form of Ehrlich tumour. In this work, we demontrated that tomatine did not induce apoptosis...
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The level of basic knowledge and skills of first aid for students in the eighth grade of primary school
Pejchal, Jaroslav ; Mareš, Jiří (advisor) ; Klicperová, Zuzana (referee)
Author: Jaroslav Pejchal, DiS. Institution: Charles University in Prague, Faculty of Medicine in Hradec Králové, Institute of Social Medicine, Department of Nursing Title of Thesis: The level of basic knowledge and skills of first aid for students in the eighth grade of primary school Thesis supervisor: Prof. PhDr. Jiří Mareš, CSc. Page of number: 116 Number of attachments: 5 Year bachelor thesis defense: 2015 Key words: adolescents, first aid, resuscitation, bleeding, coma, shock, trauma, Research My bachelor's thesis deals with the first aid and its knowledge or lack of it among pupils of the 8th form of the basic school. Selected chapters from the first aid and contact of pupils with them during their education and free time activities are described in theoretical part of my thesis. The research part of the thesis tries to find out how effective are first aid lectures for the 8th graders. Whether they can improve pupil's knowledge and skills in first aid or not. 60 pupils of 8th form from one basic school formed the research set. Results from the post-test questionnaire showed improvement in 10 score questions but deterioration in another 6. Concerning difference between sexes, females performed better (8 improvements against 5 deteriorations and 3 without changes) than males (7 improvements...
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Interactions of membrane transporters with drugs in the placenta and pancreatic ductal adenocarcinoma
Jirásková, Lucie ; Červený, Lukáš (advisor) ; Mičuda, Stanislav (referee) ; Pejchal, Jaroslav (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Mgr. Lucie Jirásková Supervisor: doc. PharmDr. Lukáš Červený, Ph.D. Title of doctoral thesis: Interactions of membrane transporters with drugs in the placenta and pancreatic ductal adenocarcinoma Membrane transporters are found throughout the body, where they are responsible for many vital functions. Important representatives of membrane transporters are P-glycoprotein (ABCB1), Breast cancer resistance protein (ABCG2) and multidrug resistance-associated protein 2 (ABCC2) belonging to the ATP-biding Cassette (ABC) family. Nucleoside transporters belonging to Solute Carriers family (SLC) transporters represent another important group. It has been well evidenced that these transporters also affect drug disposition and contribute to tumor resistance to anticancer therapy. Over working on this dissertation thesis, we investigated the mentioned transporters (with special focus on nucleoside transporters) in complex fashion. We described the expression profile of nucleoside transporters in the placenta at different stages of gestation. We also examined whether the expression of nucleoside transporters changes depending on the degree of differentiation or can be affected epigenetically, and we...
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Interactions of membrane transporters with drugs in the placenta and pancreatic ductal adenocarcinoma
Jirásková, Lucie ; Červený, Lukáš (advisor) ; Mičuda, Stanislav (referee) ; Pejchal, Jaroslav (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Mgr. Lucie Jirásková Supervisor: doc. PharmDr. Lukáš Červený, Ph.D. Title of doctoral thesis: Interactions of membrane transporters with drugs in the placenta and pancreatic ductal adenocarcinoma Membrane transporters are found throughout the body, where they are responsible for many vital functions. Important representatives of membrane transporters are P-glycoprotein (ABCB1), Breast cancer resistance protein (ABCG2) and multidrug resistance-associated protein 2 (ABCC2) belonging to the ATP-biding Cassette (ABC) family. Nucleoside transporters belonging to Solute Carriers family (SLC) transporters represent another important group. It has been well evidenced that these transporters also affect drug disposition and contribute to tumor resistance to anticancer therapy. Over working on this dissertation thesis, we investigated the mentioned transporters (with special focus on nucleoside transporters) in complex fashion. We described the expression profile of nucleoside transporters in the placenta at different stages of gestation. We also examined whether the expression of nucleoside transporters changes depending on the degree of differentiation or can be affected epigenetically, and we...
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The iron disposition regulates liver homeostasis of cholesterol and bile acids
Prašnická, Alena ; Mičuda, Stanislav (advisor) ; Pejchal, Jaroslav (referee) ; Večeřa, Rostislav (referee)
Changes in the iron content are among the most common metabolic diseases with a number of possible pathophysiological consequences for various body functions. The phenomenon accompanying these situations is the change in cholesterol homeostasis with possible extension to bile acids (BA), ie major executive and regulatory molecules in the metabolism of endobiotics, what can play an important role in associated organ dysfunctions. Since there was only a minimal amount of information in this area, the aim of this work was to evaluate the effect of iron overload and deficiency on the processes involved in BA turnover with the identification of involved molecular mechanisms. The first assessed field was the evaluation of iron deficiency (ID) using a suitable rat model, where ID was induced by a specific diet. This has demonstrated a significant inducing effect on both classical and alternative pathways for BA synthesis from cholesterol. Together with the induction of cholesterol biliary secretion in ID group it led to statistically significant decrease of plasma cholesterol concentrations. The subsequent BA-dependent choleretic effect was induced by their increased liver disposition, without affecting the expression of corresponding transporters, as verified by the kinetic study with 3 H-taurocholate....
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The Iron Disposition Regulates Liver Homeostasis of Cholesterol and Bile Acids
Prašnická, Alena ; Mičuda, Stanislav (advisor) ; Večeřa, Rostislav (referee) ; Pejchal, Jaroslav (referee)
Changes in the iron content are among the most common metabolic diseases with a number of possible pathophysiological consequences for various body functions. The phenomenon accompanying these situations is the change in cholesterol homeostasis with possible extension to bile acids (BA), ie major executive and regulatory molecules in the metabolism of endobiotics, what can play an important role in associated organ dysfunctions. Since there was only a minimal amount of information in this area, the aim of this work was to evaluate the effect of iron overload and deficiency on the processes involved in BA turnover with the identification of involved molecular mechanisms. The first assessed field was the evaluation of iron deficiency (ID) using a suitable rat model, where ID was induced by a specific diet. This has demonstrated a significant inducing effect on both classical and alternative pathways for BA synthesis from cholesterol. Together with the induction of cholesterol biliary secretion in ID group it led to statistically significant decrease of plasma cholesterol concentrations. The subsequent BA-dependent choleretic effect was induced by their increased liver disposition, without affecting the expression of corresponding transporters, as verified by the kinetic study with 3 H-taurocholate....
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