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Continuous measurement of blood pressure
Kopčil, Petr ; Chmelař, Milan (referee) ; Nováková, Zuzana (advisor)
This paper deals with the physiology of cardiovascular system, explains elementary principles related to blood flow physiology and describes some basic mechanisms for regulation and blood pressure measurement. The paper also includes a description of the medical device, known as the Finometer (FMS, Netherlands), for continuous non-invasive blood pressure measurement and suggests a way to data export from this device to a text file. It introduces user friendly application to manage recorded data written in MATLAB. There is a statistical test to assess the difference between two statistical data files in the last chapter of this paper which includes a comparison our results with studies made in Czech Republic and other countries too.
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Cardiotoxic effects of anthracyclines in oncological treatment
Tekáčová, Kateřina ; Horníková, Daniela (advisor) ; Vávra, Jiří (referee)
Anthracyclines are antitumor antibiotics used during chemotherapy in cancer patients. Treatment with anthracyclines has good results but a side effect is significant cardiotoxicity. This bachelor thesis describes the mechanisms of action of anthracyclines which are essential in cancer therapy and may be risky for patients. The thesis also defines the term of cardiotoxicity and summarizes factors that may increase the risk of cardiotoxicity. The most commonly used agents in the anthracycline series are briefly described. Cardiotoxicity can be detected by cardiac markers, especially particular troponin and diagnostic methods. The last chapter describes the groups of substances that reduce the cardiotoxic effects of anthracyclines. Key words: heart, anthracyclines, cardiotoxicity, chemotherapy, onkology treatment
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The effect of resveratrol and gambogic acid on the DNA damage caused by daunorubicin in neonatal rat cardiomyocytes.
Mašín, Martin ; Jirkovská, Anna (advisor) ; Pávek, Petr (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Martin Mašín Supervisor: PharmDr. Anna Jirkovská, Ph.D. Title of diploma thesis: The effect of resveratrol and gambogic acid on the DNA damage caused by daunorubicin in neonatal rat cardiomyocytes. DNA Topoisomerases comprise a family of enzymes that are able to alter DNA topology by transient single- or double-strand breaks (DSB) during fundamental processes such as replication and transcription. Inhibition of topoisomerase II (TOP II) is the main mechanism of action of some antitumour drugs, such as anthracyclines (ANT; e.g., daunorubicin). They stabilize the DNA-TOP II complex, leading to the formation of DSBs and later to apoptosis. Other inhibitors, that interact with the enzyme without the DSB formation, can modulate the effect of ANT. In this thesis, we studied the DNA damage caused by daunorubicin (DAU) and its main metabolite daunorubicinol (DAUnol) and the effect of two naturally-derived compounds and TOP II catalytic inhibitors resveratrol (RES) and gambogic acid (GA) in neonatal rat cardiomyocytes. The DNA damage was determined as the extent of histone H2AX phosphorylation (γ-H2AX) and by Comet Assay. It can be concluded that both DAU and DAUnol (1,2 μM) exhibit DNA damage that is...
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The effect of resveratrol and gambogic acid on the DNA damage caused by daunorubicin in neonatal rat cardiomyocytes.
Mašín, Martin ; Jirkovská, Anna (advisor) ; Pávek, Petr (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Martin Mašín Supervisor: PharmDr. Anna Jirkovská, Ph.D. Title of diploma thesis: The effect of resveratrol and gambogic acid on the DNA damage caused by daunorubicin in neonatal rat cardiomyocytes. DNA Topoisomerases comprise a family of enzymes that are able to alter DNA topology by transient single- or double-strand breaks (DSB) during fundamental processes such as replication and transcription. Inhibition of topoisomerase II (TOP II) is the main mechanism of action of some antitumour drugs, such as anthracyclines (ANT; e.g., daunorubicin). They stabilize the DNA-TOP II complex, leading to the formation of DSBs and later to apoptosis. Other inhibitors, that interact with the enzyme without the DSB formation, can modulate the effect of ANT. In this thesis, we studied the DNA damage caused by daunorubicin (DAU) and its main metabolite daunorubicinol (DAUnol) and the effect of two naturally-derived compounds and TOP II catalytic inhibitors resveratrol (RES) and gambogic acid (GA) in neonatal rat cardiomyocytes. The DNA damage was determined as the extent of histone H2AX phosphorylation (γ-H2AX) and by Comet Assay. It can be concluded that both DAU and DAUnol (1,2 μM) exhibit DNA damage that is...
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Continuous monitoring of anthraquinone-based anticancer drugs by amperometric technique
Skalová, Štěpánka ; Fischer, J. ; Barek, J. ; Navrátil, Tomáš ; Krejčí, J. ; Kučerová, R. ; Vyskočil, V.
This contribution is focused on the development of electroanalytical methods for the monitoring of anthraquinone-based anticancer drugs in physiological solution by combination of liquid-flow system and dialysis catheter, possibly inserted into blood circulation of patients. For this purpose, amperometric detection with dual glassy carbon electrode was developed and derivate of these drugs, anthraquinone-2-sulphonate, was used as a model compound. Two different flow rates of carrier solution (physiological solution) were tested (specifically, 1 and 5 mu L min(-1)) and the dependence of peak currents of anthraquinone-2-sulphonate on its concentration was verified
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Detection of iron-induced proteins and their effect on anthracycline production in submerged culture of Streptomyces coeruleorubidus
MICHALCOVÁ, Zuzana
In this bachelor's thesis, proteins from the group of enzymes - esterases and their possible induction after the addition of iron to the culture medium were analyzed. Furthermore, the effect of the addition of Fe2+ cations on daunomycin production under submersion cultivation conditions of Streptomyces coeruleorubidus culture was evaluated. The work is divided into two parts. The first part introduced the genus actinobacteria called Streptomyces, their occurrence, properties and possible benefits due to the production of secondary metabolites. In the second, experimental part, the use of the Streptomyces coeruleorubidus strain was described. The effect of iron addition was evaluated by HPLC analysis and native polyacrylamide electrophoresis (native PAGE). HPLC analysis showed that the addition of iron in the form of FeSO4 to the medium increased daunomycin production by approximately 21.5-fold. During native PAGE and after staining, proteins, i.e. esterases, most likely from the groups of and esterases, were detected. Those were more or to a greater extent produced by the Streptomyces coeruleorubidus if the medium contained iron.
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Antiproliferative and cardioprotective potential of the newly synthetised analogues of dexrazoxane.
Gavurová, Lucie ; Jirkovská, Anna (advisor) ; Čečková, Martina (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Lucie Gavurová Supervisor: PharmDr. Anna Jirkovská, PhD. Title of diploma thesis: Antiproliferative and cardioprotective activity of novel dexrazoxane analogues Anthracycline antibiotics (such as daunorubicin, doxorubicin or epirubicin) forms the basis of anticancer therapy in many hematological malignancies and solid tumors. However, their clinical use is limited by adverse effects. The most serious of these effects is chronic form of anthracycline-induced cardiotoxicity. Dexrazoxane is the only one clinically approved cardioprotective agent against anthracycline cardiotoxicity so far. Despite its well-evidenced cardioprotective effects, dexrazoxane use is very limited due to its possible adverse effects. The the synthesis of novel analogs of might contribute to understanding of the relationship between structure and effects of dexrazoxane. Finally, this approach could lead to the synthesis of structure with better pharmacological properties. The aim of this diploma thesis was to assess the antiproliferative activity of novel analogues of dexrazoxane (JR-281B, JR-311, JR-306A, JR-306B, JR-232 and JR-312B), and the study of the influence on the antiproliferative effect of anthracyclines....
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The cancer cell proteome and its changes after anti-cancer drug treatment
Tylečková, Jiřina
Cancers represent a group of unprecedented heterogeneous diseases and currently available anti-cancer therapies provide highly variable efficacy with unsatisfactory cure rates. A wide range of proteomic technologies are being used in quest for newer approaches which could significantly contribute to the discovery and development of selective and specific cancer biomarkers for monitoring the disease state and anti-cancer therapy success. Taking into consideration the above aspects, this research was undertaken to study cancer cell proteomes and their changes after anti-cancer treatment with specific focus on: (a) response to conventional anthracycline/anthracenedione drugs with respect to their different clinical efficacy and (b) identification of novel targets for therapy in cancer cells resistant to biological drugs such as inhibitors of (b1) cyclin-dependent kinases and (b2) Aurora kinases. This study identified several interesting key aspects related to the effects of daunorubicin, doxorubicin and mitoxantrone. With the main focus on early time intervals when the influence of apoptosis is minimised, changes common for all three drugs belonging mainly to metabolic and cellular processes were observed. More importantly, significant changes in proteins involved in the generation of precursor...
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The effect of acalabrutinib and ibrutinib on the efficacy of daunorubicin in cancer cells.
Čermáková, Lucie ; Novotná, Eva (advisor) ; Hofman, Jakub (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Lucie Čermáková Supervisor: RNDr. Eva Novotná, Ph.D. Title of diploma thesis: The effect of acalabrutinib and ibrutinib on the efficacy of daunorubicin in cancer cells Leukemia presents malignant diseases of hematopoiesis, which essence is the malignant transformation of a hematopoietic stem cell at various levels of maturation and increased proliferative activity. Chemotherapy is the gold standard in the treatment of leukemia. One of the many treatments is the use of anthracycline chemotherapeutics, especially daunorubicin (DAU). Anthracyclines are widely used in clinical practice but have high cardiotoxic effects that limit their dosage. One of the main causes of side effects is the reduction of an anthracycline chemotherapeutic to the appropriate toxic metabolite, which accumulates in the heart. Carbonyl, reducing enzymes from the superfamily aldo-ketoreductase (AKR), and short-chain dehydrogenase/reductase (SDR) are involved in this reduction. At the same time, carbonyl reducing enzymes, has been shown to be involved in the mechanisms that cause tumor cells to be resistant to anthracyclines, thereby reducing the inhibition of the growth of these cells. In the diploma thesis we found that...
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The effect of the proteasome inhibition of the antiproliferative effect of anthracycline antibiotics.
Kroupová, Jana ; Jirkovská, Anna (advisor) ; Čečková, Martina (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Jana Kroupová Supervisor: PharmDr. Anna Jirkovská, Ph.D. Title of diploma thesis: The effect of the proteasome inhibition of the antiproliferative effect of anthracycline antibiotics Anthracycline antibiotics (daunorubicin, doxorubicin) belong to the most effective antitumor drugs. In current clinical practice they are used mostly in the combinations with either "classical" or new targeted antitumor drugs. The proteasome inhibitors (bortezomib and carfilzomib) are also viewed as a part of new "targeted" antitumor drugs. The proteasome is a multienzyme complex in eukaryotic cells which is responsible for intracellular degradation of proteins. The proteasome inhibitors have been largely used in the therapy of multiple myeloma, but their potential has been also studied in the case of other malignancies. Their use in the combination with anthracyclines could be a possible alternative in the therapy of some tumor illnesses, but the effect of combination of anthracyclines and proteasome inhibitors on tumor cells have not been sufficiently explained. The anthracycline therapy is also accompanied by serious adverse side effect - the cardiotoxicity, which potential could be influenced by the...
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