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Antifungal Drug Discovery: Focus on Incrustoporin Derivatives
Silva, Luis André Vale ; Buchta, Vladimír (advisor) ; Heidingsfeld, Olga (referee) ; Hamal, Petr (referee)
1 CONCLUSIONS In the context of Medical Mycology today, the development of new more effective antifungal agents is a priority. In fact, there are still only about six drugs in use to treat invasive fungal infections, concretely the polyene amphotericin B (including its new lipidic formulations), the antimetabolite flucytosine, the triazoles fluconazole, itraconazole, and voriconazole, and the echinocandin caspofungin. Simultaneously, the incidence of invasive opportunistic mycoses has been increasing steadily with the increasing number of immunocompromised patients, caused both by HIV (human immunodeficiency virus) infection and AIDS and the development of medical techniques, particularly referring to oncology or transplant patients. In this setting, the relevance of the development of new antifungal agents and, hence, our work presented here, is easily understandable. The group of the acyloxymethylated incrustoporin derivatives is now in a higher stage of development, after being previously studied concerning structure-antifungal activity relationship and tuning of antifungal activity. Our work has shown the best derivatives from the group, compounds LNO6-22, LNO15-22, and LNO18-22, to have broad spectrum in vitro antifungal activity and high potency, inhibiting growth of a variety of pathogenic yeasts and...
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Molecular methods used for taxonomy and epidemiology of dermatophytes
Čmoková, Adéla ; Hubka, Vít (advisor) ; Hamal, Petr (referee)
In my bachelor thesis I have dealt with the role and aplication of the molecular methods in the taxonomy and epidemiology of the dermatophytes and the question of the species concepts in dermatophytes. In the first part, I focused on the evaluation of the advantages and disadvantages of the recent species concepts and their problematic application in dermatophytes. The second part is focused on the molecular methods that used genetic markers for phylogenetic analysis and species delineation within dermatophytes, e.g. the PCR-RFLP method, PCR-fingerprinting and DNA sequencing. I have evaluated the dicrimination power of the particular DNA sequence loci to distinguish closely related species. In the last part, I have summarized the molecular methods that have been used in the typization at the intraspecific level, e.g. microsatelite analysis, PCR-fingerprinting, multilocus sequence typing.
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Účinek antimikrobiálních prostředků na mikroorganismy dutiny ústní
Kudiyirickal, Marina George ; Koberová Ivančaková, Romana (advisor) ; Hamal, Petr (referee) ; Poleník, Pavel (referee)
Disease of the pulp and periodontium which constitute the vast proportion of odontogenic infections are mainly caused by the endogenous bacterial microbiota in the oral cavity while non odontogenic infections in the same area vary depending on the nature and site of infection. The rational use of antibiotic is important to prevent development of resistant strains and other side effects of drugs. Aim: To investigate (i) the prevalence of bacterial species in oral samples of patients with bacterial infection reporting at the Dept of Dentistry (1996- 2007), (ii) to assess the age and sex predilection and , (iii) and species specific relationships, and (iv) to determine the susceptible-resistant biotype profile of the bacterial isolates from odontogenic and non odontogenic infections. Materials and methods: Laboratory and clinical data of patient's electronic files at Dept of Microbiology, Faculty of Medicine and Teaching Hospital in Hradec Králové for the years 1996-2007 were evaluated retrospectively. Results: Bacterial orofacial odontogenic or non odontogenic infection was detected in a total of 678 patients with 350 males (51.6%) and 328 females (48.4%). The bacterial isolates included 48 bacterial species with predominance of facultative anaerobes which accounted for 78.5% (n= 1263) and obligate anaerobes...
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Laboratory diagnosis of Candida infections
Vejsová, Marcela ; Buchta, Vladimír (advisor) ; Mencl, Karel (referee) ; Hamal, Petr (referee)
Pathogenic Candida species represent the most common fungal etiology of human opportunistic infections, particularly among hospitalized patients. After decades of increasing morbidity and mortality of candidiasis, the proportion of Candida infections had become to stop and the shift of spectrum of Candida species has started to be evident. Apart from a predominating position of C. albicans, there is a growing number of non-albicans Candida species (e.g. C. glabrata, C. tropicalis) as causative agents of yeast infections. Mycologists are faced up new challenges of rapid detection and precise identification of fungal isolates including antifungal susceptibility evaluation. Goal of the study was to confirm usefulness of rapid tests in laboratory diagnostics of C. albicans and elaborate an alternative method of classical germ tubes test in serum. The results of experiments showed the use of chromogenic media useful and reliable as well as the test of induction of germ tubes. The comparative tests showed that serum can be replaced with chemically defined NYP medium without loss of high of specificity and sensitivity of the test. Main part of experiments was focused on optimalization of methodology of in vitro antifungal susceptibility testing. Etest and disk diffusion test are very reliable tests for...
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Antifungal Drug Discovery: Focus on Incrustoporin Derivatives
Silva, Luis André Vale ; Buchta, Vladimír (advisor) ; Heidingsfeld, Olga (referee) ; Hamal, Petr (referee)
1 CONCLUSIONS In the context of Medical Mycology today, the development of new more effective antifungal agents is a priority. In fact, there are still only about six drugs in use to treat invasive fungal infections, concretely the polyene amphotericin B (including its new lipidic formulations), the antimetabolite flucytosine, the triazoles fluconazole, itraconazole, and voriconazole, and the echinocandin caspofungin. Simultaneously, the incidence of invasive opportunistic mycoses has been increasing steadily with the increasing number of immunocompromised patients, caused both by HIV (human immunodeficiency virus) infection and AIDS and the development of medical techniques, particularly referring to oncology or transplant patients. In this setting, the relevance of the development of new antifungal agents and, hence, our work presented here, is easily understandable. The group of the acyloxymethylated incrustoporin derivatives is now in a higher stage of development, after being previously studied concerning structure-antifungal activity relationship and tuning of antifungal activity. Our work has shown the best derivatives from the group, compounds LNO6-22, LNO15-22, and LNO18-22, to have broad spectrum in vitro antifungal activity and high potency, inhibiting growth of a variety of pathogenic yeasts and...
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