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Pyrazine Derivatives as Potential Drugs IV.
Kisza, Daniel ; Doležal, Martin (advisor) ; Miletín, Miroslav (referee)
Title: Derivates of Pyrazine as potential drugs IV Author: Daniel KISZA In my diploma thesis I summarize a research that refers to the topic of the tuberculosis in the Czech Republic as well as in the world. It includes the description of the causal agent and also the prevalence, the incidence and the treatment of the disease. This literature retrieval also includes questions related to the multidrug-resistant tuberculosis (MDR-TB) and the extensively drug resistant tuberculosis (XDR-TB) with the inclusion of the treatment strategies. I also presented ten substances with the character of the substituted ester of pyrazinecarboxylic acid that haven't been described yet and which I synthesized. As a basic acid for esterification I used 6-[(3-methylphenyl)amino]pyrazine-2-carboxylic acid. All these substances were synthesized using the microwave system CEM Discover with auto sampler Explorer 24. In the next step they have been separated and purified using the CombiFlash® Rf. The melting point has been defined for each of those substances and the IR, 1 H, 13 C NMR spectra have been analyzed. All the compound were tested for biological activity.
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Analytical determination of active compounds by liquid chromatography III.
Doskočilová, Marie ; Sochor, Jaroslav (advisor) ; Mokrý, Milan (referee)
ANALYTICAL DETERMINATION OF ACTIVE COMPOUNDS BY LIQUID CHROMATOGRAPHY III. Diploma Thesis Marie Doskočilová Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Chemistry and Drug Control, Heyrovského 1203, Hradec Králové In this thesis, the development of suitable conditions for analytical sample oxazepam in rabbit blood by high-performance liquid chromatography. For treatment of biological material used solid phase microextraction. Analysis carried out on a C18 column. Mobile phase consisted of methanol and water mixture in the ratio 80:20. UV detector was used in the wavelength of 230 nm. Quantitative evaluation was carried out by internal standard, which was diazepam. Oxazepam was isolated from biological material using SPME. For extraction was used the fiber PDMS / DVB, the desorption medium was methanol. Sorption and desorption time lasted 13 minutes. Extraction efficiency was 5, 9%. For quantitative evaluation of calibration curve was prepared, which were subsequently verified by model samples.
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Development of LC/MS/MS method for determination of ambrisentan, midazolam and its metabolite in human plasma
Klivický, Michal ; Kučera, Radim (advisor) ; Štěrbová, Petra (referee)
Development of LC/MS/MS method for determination of ambrisentan, midazolam and its metabolite in human plasma Diploma thesis Michal Klivický Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Chemistry and Drug Control Heyrovského 1203, Hradec Králové. Ambrisentan (ABT) is a new potent drug for treatment of pulmonary arterial hypertension, which is metabolized by CYP3A4. Pharmacokinetic profile of midazolam (MDL) and its main metabolite 1-hydroxymidazolam (OH-MDL) can be used as a marker of CYP3A4 activity. Simultaneous determination of ambrisentan, midazolam and 1-hydroxymidazolam is advantageous for studying of potential influence of CYP3A4 induction or inhibition on ambrisentan pharmacokinetics. HPLC/MS/MS method for their analysis in human plasma was developed and validated. After solid phase extraction on a Strata-X (Phenomenex) SPE column, the analytes were separated on a Synergi MAX-RP (150×4.6 mm, 4 µm) (Phenomenex) analytical column using isocratic elution with acetonitrile/5mM ammonium acetate 41:59 (v/v) as a mobile phase. Detection was achieved using tandem mass spectrometry on a triple quadrupole mass spectrometer. Ambrisentan-d3, midazolam-d5 and 13 C3-1-hydroxymidazolam were used as internal standards. The calibration curves were linear...
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Quality of Life and Its Understanding by Mental Health Patients in the Paprsek nadeje Centre
BARTOŠÍKOVÁ, Radka
In this thesis I would like to acquaint the reader with the impact of mental illness on human. In my thesis I focus on the psychosocial impact of the illness in the form of the assistance to an ill person, the quality of interpersonal relationships and quality of social interactions linked to the stigma. The essence of research in the social field were the findings concerning the living conditions of the client, client's activities and leisure time activities or the manners of support in illness. An important task of the client was to respond to questions about the hardships in life. The paper also deals with the knowledge of the physical, mental and spiritual qualities. It focuses on the comparison and awareness of the role of illness and pharmacotherapy as a limiting factor in the perception of quality life. It refers to the material conditions of these people, emerging drug addiction and subjective values and a feeling of well lived life in general. An important element of my research is to detect clients? life goals and to record their life satisfaction using "scale of life satisfaction." My goal was to map the real quality of life of the clients of the centre Paprsek naděje and the key aspects of the experience of life and how the meeting of the individual needs of the client affects the quality of life from their own perspective. The results were then evaluated and compared with Maslow's hierarchy of needs. The thesis is divided into two parts, theoretical and practical. The theoretical part deals with the classification of mental illnesses, their prognosis and treatment. I emphasize the disorder schizophrenia as a contemporary phenomenon, and finally the quality of life and the various aspects that affect it - the status of the ill person in the family, society, work and isolation. The empirical part is devoted to the research itself. For research I used qualitative research methods and techniques of semi-structured interview supplemented by observations. The research group consists of 5 clients of the centre Paprsek naděje in the age range of 28-59 years. I carried out one pilot study before the research itself. The resulting data were processed and put in tables and graphs, evaluated and compared in the discussion and conclusion. Part of the research was realized using the Schedule for the Evaluation of Individual Quality of Life, SEIQoL. Using this method, I examined individual life goals of each client, their importance and satisfaction with their achievements. Overall I responded to one main research question and two sub-questions. I consider the findings of abnormal invalidity and unemployment, high levels of stigmatizing experience, lack of active free time and physical activity, emerging drug addiction or lack of interpersonal relationships as the crucial results negatively affecting quality of life. Physical decrepitude is always a present component. The research also showed occasional unfamiliarity with diagnosis. Positives can mainly be seen in family support and in the quality of family relationships, also in sufficient material sources and in family and spiritual priorities. It is essential that compared with the Maslow's hierarchy, it was found that it has preserved its traditional arrangement in the process of meeting the needs. The content of individual needs was however varied in each of its individual parts. I have also learned that mental illness limits clients greatly for example in the context of culture and their interests and that there are also limitations to the parental instinct caused by fear of the large amount of responsibility and the impact of their illness to their children. An unexpected finding was the satisfaction of all clients with material sources. Similarly, the clients see their mental illness as a certain way of realizing satisfaction.
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Prolyl endopeptidase of the blood fluke Schistosoma mansoni
Fajtová, Pavla ; Konvalinka, Jan (advisor) ; Ryšlavá, Helena (referee)
Prolyl endopeptidase SmPEP from the blood fluke Schistosoma mansoni is investigated here for the first time. This enzyme is potentially interesting as a drug target for the treatment of schistosomiasis. SmPEP was detected in the extract of adult worms by enzyme activity and immunoreactivity. Enzymatically active SmPEP was produced in the E. coli expression system and was chromatographically purified. The pH optimum of recombinant SmPEP was about 8. Substrate specificity analysis revealed that SmPEP cleaved peptide substrates by endopeptidase activity, however, macromolecular substrates were not fragmented. The residue preferences in the positions P3 to P1' were determined using synthetic fluorogenic peptide substrates. SmPEP was found to be highly sensitive to the inhibition by Z-Ala-Pro-CMK and Z-Arg-Pro-CHO. Primary screening of crystallization conditions for recombinant SmPEP was performed. " (In Czech)"
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Gene Therapy of CML: Experimental Vaccines against Bcr-abl-transformed Cells
Lučanský, Vincent
Chronic myeloid leukemia is malignant disease characterized by myeloproliferative clonal expansion of hematopoietic stem cell. It is causally associated with the formation of the so called Philadelphia chromosome and production of its specific product, the chimeric BCR-ABL protein. The amino acid sequence of the fusion region is unique, implying that the BCR-ABL protein carries tumor specific antigen. Currently imatinib mesylate dominates the treatment of CML. It is well tolerated and when compared to the other drugs used, it prolongs the life expectancy significantly. Unfortunately, it is not capable to cure the disease. The only potentially curative approach nowadays is the bone marrow transplantation; however, it is connected with a relatively high morbidity and mortality. Moreover, it is available only to a minority of the patients. Under these circumstances the need for the development of a relatively safe and generally available treatment is understandable. Immunotherapy could be such a treatment. Several experimental vaccines based on BCR-ABL sequence were developed and tested in mice in our institute. The DNA vaccines used were carrying sequences coding for the whole BCR-ABL protein, or for 25 amino acids long junction region (these DNA sequences were fused with adjuvant genes such as...
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Trends in the Consumption of a chosen ATC Group A10AA (inhibitors HMG-CoA reductase) in the period 2005-2015 in the Czech Republic
Freimann, Antonín ; Lešetický, Ondřej (advisor) ; Železo, Eduard (referee)
The thesis deals with trends of drug consumption for the ATC group C10A (HMG-CoA reductase) in the Czech Republic in the years 2005 - 2015. The goal of this work is to analyse the consumption of statins (cholesterol lowering drugs), as well as to analyse the consumption trends (expressed in terms of prescribed daily doses) and subsequently explain the causes of the detected trends. The main method used in this work is the analysis and interpretation of data provided by the State Institute for Drug Control (SUKL). Individual consumption data sets are compared to each other and global trends are inferred based on the obtained results. In the practical part I analyse the consumption for the individual ATC groups according to their increasing lipid-lowering efficacy, according to the pharmaceutical companies involved and according to the experts' recommendations (within the framework of cardiovascular disease treatment). The conclusion of my work shows that the overall drug consumption for the the studied ATC group (given by the DDD/package total) was steadily increasing during the studied period while the consumption expressed in financial units was decreasing (ie. the financial burden on the health system was reduced). The total number of sold packages shows a slight decrease due to the sale of bigger packages with more powerful statins during the studied period.
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Chronic Obstructive Pulmonary Disease ant its Treatment
Vrátná, Sandra ; Vopršalová, Marie (advisor) ; Žáčková, Pavla (referee)
1 ABSTRACT The aim of my thesis was a comprehensive view of COPD as a separate nosological entity. A substantial section focuses on current therapy, which are listed by category as concessional and stability of drugs including their mechanism of action. Education and smoking prevention play major role during the non- pharmacological therapy , as well as the rehabilitation, which is not yet very common, but it may contribute significantly to patientś health improving. The work is also illustrative of the disease compared with bronchial asthma because of the significant similarities of these diseases, their possible replacements and overlays number of syndromes that may complicate the diagnosis of any disease. A separate chapter is devoted to innovations in treatment, which lead to new possibilities in the combination of drugs for immunotherapy, but also necessary for long-acting drugs that promote patient compliance and is seeking to increase their comfort during therapy. Given that most drugs are administered by inhalation, indicated in my work with the issue of inhalation systems, their separation and the available tools offered by the Czech market.
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Modern druh treatment of bronchial asthma
Schnitterová, Terezie ; Vopršalová, Marie (advisor) ; Melicharová, Ludmila (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Farmacology and Toxicology Candidate: Terezie Schnitterová Supervisor: PharmDr. Marie Vopršalová, CSc. Title of diploma thesis: Modern Pharmacotherapy of Asthma Bronchiale The purpose of this search thesis is to analyse the most common chronic in- flammatory disorder of the airways - asthma bronchiale. The issues are discussed comprehensively and the focus of this thesis is on the current view of treatment, its possibilities and perspectives. The extraordinary attention is devoted to occupatio- nal asthma and especially to the most common causal agents which one can meet in a certain occupation with. Epidemiology, etiopathogenesis, clinical manifestations and diagnostic methods are described in the first part of this thesis. Various groups of antiasthmatic medi- caments, inhaler preventive and symptomatic drug delivery systems including, are discussed in following separate chapters. The possibilities of treatment with new promising asthma drugs are also mentioned here. Keywords: asthma, occupational asthma, asthma treatment, inhalers
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