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In vitro screening of potential antimycobacterial compounds against fast growing strains of Mycobacterium genus
Židková, Lenka ; Janďourek, Ondřej (advisor) ; Jílek, Petr (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Study program: Specialist in Laboratory Methods Candidate: Bc. Lenka Lyčková Supervisor: PharmDr. Ondřej Janďourek, Ph.D. Title of diploma thesis: In vitro screening of potential antimycobacterial compounds against fast growing strains of Mycobacterium genus The aim of this work is to determine the efficacy of new compounds for possible treatment of tuberculosis in the future. A microdilution broth method with already proven procedure on Mycobacterium aurum and Mycobacterium smegmatis strains was used to determine the minimum inhibitory concentration of compounds. The theoretical part summarizes the epidemiological situation of recent years with global trends in the incidence and mortality of tuberculosis in the world and in the Czech Republic, including prospective plans for remediation in the time horizon. Mycobacteria are described in the main representation with M. tuberculosis. Tuberculosis disease - its history, forms, diagnosis and treatment with antituberculotics, which are divided according to the use lines, new drugs and drugs in development. The experimental part contains qualitative and quantitative methods of testing mycobacteria and captures the microdilution broth method used in...
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Pathogenesis of infectious disease caused by bacterium Mycobacterium tuberculosis
Doležalová, Klára ; Janďourek, Ondřej (advisor) ; Kovařík, Miroslav (referee)
Charles University Faculty of Pharmacy in Hradec Kralove Department of Biological and Medical Sciences Study programme: Bioanalytical laboratory diagnostics in health care Author: Bc. Klára Doležalová Supervisor of diploma thesis: PharmDr. Ondřej Janďourek, Ph.D. Title of diploma thesis: Pathogenesis of infectious disease caused by bacterium Mycobacterium tuberculosis The theoretical part of this diploma thesis is concerned about tuberculosis where the main part of the thesis is focused on pathogenesis of this disease. Tuberculosis is recognized as highly infectious disease leading to the total exhaustion of the organism. The main causative agent of the above mentioned disease is Mycobacterium tuberculosis, which is transmitted to respiratory tract via inhalation of droplets from infected person and leads to the granuloma formation. For tuberculosis is typical a creation of granulomas, mainly with caseous necrosis. Highly important is accurate diagnosis and appropriately chosen treatment. The treatment consists of a long-term administration of antituberculotic drugs in combinations. The development of the resistance to one or more antituberculotics is adverse complication within the treatment procedure. The experimental part of this work pays attention to the testing of antimycobacterial activity...
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Mycobacterium tuberculosis - structure and functions of the cell wall
Kukrálová, Simona ; Janďourek, Ondřej (advisor) ; Jílek, Petr (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Study program: Bioanalytical laboratory diagnostics in healthcare Candidate: Bc. Simona Kukrálová Supervisor: PharmDr. Ondřej Janďourek, Ph.D. Title of diploma thesis: Mycobacterium tuberculosis - structure and functions of the cell wall Mycobacterium tuberculosis is an intracellular pathogen that causes a disease called tuberculosis, which, along with other selected diseases, is still one of the leading causes of mortality in the world. It is estimated that more than a million people succumb to the disease each year. The remarkable structure of the cell wall of mycobacteria has a great influence on the treatment of tuberculosis itself, together with the ever-increasing incidence of multidrug- resistant and extensively resistant strains, especially in Mycobacterium tuberculosis. The research of mycobacteria is given great attention. Efforts to find new substances with antimycobacterial effect acting on individual components of the cell wall, preferably on the cell wall as a complex, are actual and are part of national as well as international programs. Theoretical part of this diploma thesis deals with current knowledge about mycobacteria with emphasis on cell wall, epidemiology of tuberculosis...
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Derivative of Aminobenzoic Acids as Potential Antimicrobial Agents
Brokešová, Kateřina ; Krátký, Martin (advisor) ; Janďourek, Ondřej (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Candidate: Mgr. Kateřina Brokešová Consultant: PharmDr. Mgr. Martin Krátký, Ph.D. Title of Thesis: Derivatives of Aminobenzoic Acids as Potential Antimicrobial Agents The increasing resistance to previously unnecessarily used antimicrobial drugs has led to the need for search and synthesis of new drugs including Schiff bases. The rigorous thesis deals with the synthesis and subsequent characterization and evaluation of biological properties of new Schiff bases synthesized from substituted salicylaldehydes and aromatic amino acids and their derivatives (3-aminobenzoic, 3,5-diaminobenzoic acids and esters of 4-aminobenzoic acid). The prepared derivatives were evaluated for their antibacterial, antifungal and antimycobacterial activities; cytotoxicity was also investigated for the most active ones. Most of the Schiff bases exhibit antibacterial activity with minimum inhibitory concentration (MIC) from 7.81 µM, which is comparable with a standard drug bacitracin for some strains. Schiff bases appear to be more effective against Gram-positive bacteria including methicillin- resistant Staphylococcus aureus. The newly synthesized compounds are also effective against yeasts and filamentous fungi. The...
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The possibility of determination of HIV antibodies avidity for early infection detection
Diničová, Michaela ; Janďourek, Ondřej (advisor) ; Jílek, Petr (referee)
Charles University Faculty of Pharmacy in Hradec Kralove Department of Biological and Medical Sciences Study program: Specialist on Laboratory Methods Supervisor: PharmDr. Ondřej Janďourek, Ph.D. Title of diploma thesis: The possibility of determination of HIV antibodies avidity for early infection detection The determination of early HIV infection in the Czech Republic is based on a combination of results of laboratory examination, clinical examination, and information from an epidemiological report. The identification of patient in the acute phase of the disease allows to search for targeted contact to reduce further spread of HIV, as patients in the early phase of the disease are the riskiest for transmission of infection. One of the laboratory markers of the acute phase of infection is low avidity of antibodies, which expresses the strength of bonds between antigen and antibody. The determination of avidity is based on fact that avidity in recent infections is low because antibodies do not bind tightly enough to antigen and avidity increases when the immune response matures. Quantitatively, it is expressed by the avidity index, which determines what part of the antibodies (%) will remain bound in complex with the antigen after incubation with chaotropic agent, in our case with guanidine...
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Evaluation of antimicrobial effectiveness of new quaternary ammonium salt compounds
Suk, Ondřej ; Kovařík, Miroslav (advisor) ; Janďourek, Ondřej (referee)
Author: Ondřej Suk Title: Evaluation of antimicrobial effectiveness of new quaternary ammonium salt compounds Diploma thesis Charles University in Prague, Faculty of Pharmacy in Hradec Králové Study program: Pharmacy Background: The aim of the work was to evaluate antimicrobial activity of newly proposed and prepared quaternary ammonium salts. Methods: Broth microdilution method was used to measure antimicrobial activity of 8 new substances divided into three structure groups on 8 bacteria strains: Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Yersinia bercovieri, Klebsiella pneumoniae, Klebsiella pneumoniae ESBL positive and multiresistant Pseudomonas aeruginosa. Results: Out of the 3 structure groups, the highest antimicrobial potential was found with some methylmorpholine salts and benzylimidazole substituted salts. Generally, the substances were, as supposed, more efficient with the Gram-positive bacteria tribes than with the Gram-negative ones. No bactericidal effect of these substances in the concentration measured was found on the strain of multiresistant Pseudomonas aeruginosa. Conclusions: The Gram-positive strains tested are more sensitive towards the tested substances than the Gram-negative ones. In comparison with some...
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Determination the mechanism of entry F. tularensis into B lymphocytes
Hadámková, Barbora ; Konečná, Klára (advisor) ; Janďourek, Ondřej (referee)
Barbora Hadámková Determination the mechanism of entry F. tularensis into B lymphocytes Diploma thesis Charles University, Faculty Of Pharmacy in Hradec Králové Study program: Pharmacy Background: Besides processing the research with basics knowledge of the problem, the main aim of the study was the analysis of mechanism of entrance of intracellular bacteria Francisella tularensis into B cells. Methods: The B cells, which we obtained through peritoneal lavage from mice Balb/c, we blocked using antibodies individual complement receptors, B cell receptor and Fcƴ receptor. The population of the cells was infected by bacteria F. tularensis LVS/GFP opsonized by complement and/or by antibodies. Using flow cytometry we measured the percentage of infection of individual subpopulations of B cell B1a, B1b and B2 and we evaluated the influence of blocking and opsonization on the infection. Results: From the measured data, we can say that the percentage of infected B cells after infection by F. tularensis opsonized by complement is increased. This increase was more distinct in subtype of B cells B1b and B2. On the other hand, the opsonization F. tularensis by antibodies did not affect the infection. We also found out, that blocking of Fcƴ receptor has decrease the infection, if we used for infection of B cells...
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Sjögren's syndrome - anamnestic study
Rosecká, Michaela ; Jílek, Petr (advisor) ; Janďourek, Ondřej (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Student: Michaela Rosecká Supervisor: PharmDr. Petr Jílek, CSc. Title of Bachelor thesis: Sjögren's syndrome - anamnestic study Backround: The aim of this work was to get acquainted with the problems of this serious illness and the comparison of the quality of life diagnosed in the Czech Republic and abroad. Main findings: Sjögren's syndrome is an autoimmune disease with exocrine gland disorders. The pathogenesis of this disease is still unclear, but knowledge of the involvement of various cells and the pathways leading to autoimmunity is increasing. The most common symptom is dryness of the eyes and mouth, but patients often have problems with musculoskeletal or systemic damage of the body. Sjögren's syndrome brings an increased risk of developing lymphoproliferative disease. Conclusions: Attempts to create new diagnostic criteria indicate the difficulty and great interest in understanding this disease. Accurate diagnosis should be performed by laboratory diagnostics in combination with appropriate tests. Still, it is a problem to identify this disease safely and Sjögren's syndrome remains an unknown and underestimated autoimmune disease.
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Enzyme kinetic evaluation of several potential inhibitors of certain human cysteine and serine proteases
Hympánová, Michaela ; Konečná, Klára (advisor) ; Janďourek, Ondřej (referee)
IN ENGLISH Charles University Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Supervisors: prof. Dr. Michael Gütschow RNDr. Klára Konečná, Ph.D. Candidate: Michaela Hympánová Title of the diploma thesis: Enzyme kinetic evaluation of several potential inhibitors of certain human cysteine and serine proteases Background Cysteine and serine proteases are enzymes involved in many physiological processes. The imbalance between them and their endogenous inhibitors is associated with various diseases such as cancer and osteoporosis. Synthetic inactivators could be useful in the treatment of these enzyme-mediated pathological conditions. Therefore, there are ongoing attempts to develop low-molecular weight inactivators for therapeutically relevant cysteine and serine proteases. In the course of this thesis, compounds synthesized in prof. Gütschow's group were investigated as potential inhibitors of selected human proteases. They belong to imidazole compounds derived from N-protected cyclohexylalanine, 2-phenyl-7,8-dihydroimidazo[1,2- a]pyrazin-6(5H)-one derivatives, ,-unsaturated peptidomimetic compounds, carbamates, an N,N-dibenzylcrotonamide derivatives and peptoides. Aims This diploma thesis has been focused on the evaluation of new potential inhibitors against...
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Derivatives of pyrazine as potential antituberculars (preparation and study of biological properties)
Janďourek, Ondřej ; Doležal, Martin (advisor) ; Farsa, Oldřich (referee) ; Musílek, Kamil (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical chemistry and Pharmaceutical analysis Candidate Mgr. Ondřej Janďourek Supervisor Prof. PharmDr. Martin Doležal, Ph.D. Consultant PharmDr. Jan Zitko, Ph.D. Title of Doctoral Thesis Derivatives of pyrazine as potential antituberculars (preparation and study of biological properties) This work is focused on pyrazine derivatives with the structural relationship to pyrazinamide (PZA) and with the potential antitubercular effect. In the introduction, there are summarized theoretical findings about tuberculosis (TBC), its epidemiology and primarily the development of resistance to current pharmacotherapy. Brief overview of known antituberculars, novel compounds and auspicious molecules in clinical trials is outlined. PZA, which is counted among the first line antitubercular agents, is widely described due to its cardinal role in this thesis. PZA possible mechanisms of action are described together with its pharmacological profile. Finally, brief summary of already prepared derivatives of PZA is stated. Practical part of this thesis is focused on synthesis of three starting compounds (5-chloro-6-methylpyrazine-2,3-dicarbonitrile; 3-chloropyrazine-2-carboxamide; N-benzyl-3-chloropyrazine-2-carboxamide) that were...
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