Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Candidate: Bc. Nela Drnková Supervisor: Mgr. Marcela Vejsová, Ph.D. Title of diploma thesis: Evaluation of activity of potencial antifungal substances trought the use of microdilution broth method Background: The aim of this thesis was evaluation of antifungal activity of 70 substances trought the use of microdilution broth method. Substances for testing were synthesized at the Faculty of Pharmacy and they were divided into 5 groups based on chemical structure. Methods: The microdilution broth method was used for testing. The antifungal activity of substances was tested on 8 strains of yeasts and filamentous fungi: Candida albicans, C. tropicalis, C. glabrata, C. krusei, Trichosporon asahii, Aspergillus fumigatus, Absidia corymbifera a Trichophyton mentagrophytes. Results: The most active substances were in group of salicylanilide N- monosubstituted and N,N-disubstituted carbamates and thiocarbamates. The most effective substances were SAL-1L, SAL-1M, SAL-1N. They were effective on Trichophyton mentagrophytes already at concentration of 1,95 µmol.l-1 . The widest spectrum had substance GP-137, it inhibited the growth of all tested strains, but only at high concentrations. Rhodamine...

Department of Biological and Medical Sciences Faculty of Pharmacy in Hradec Králové Charles University in Prague Author: Ivana Ťapuchová Title of diploma thesis: Evaluation of activity of potentional antifungal substances through the use of microdilution broth method Supervisor: Mgr. Marcela Vejsová, Ph.D. Background: The aim of this diploma thesis was to evaluate potential antifungal activity of 52 test substances which were develope at the Department of anorganic and organic chemistry Faculty of Pharmacy in Hradec Králové Charles University in Prague. Methods: For testing we used microdilution broth method on eight strains of yeasts and filamentous fungi in the laboratory of Department of Biological and Medical Sciences. Results: Overall 26 test substances with various substituents had antifungal activity. These substances was derivates of 4-aminobenzoic acid, 4-aminosalicylic acid, 5-aminosalicylic acid and large group derivates of sulfonamids. The most sensitive strain was dermatophyt Trichophyton mentagrophytes, the least sensitive strain was filamentous fungi Absidia corymbifera. Conclusions: Despite there was observed antifungal activity in low concentrations of derivates, it is necessary to perform next tests and clinical studies to prove efficiency and safety for use. Key words: yeasts,...

Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Title of thesis: Evalution of activity of potentional antimycotic substances through the use of microdilution broth method III Autor of thesis: Alena Zavřelová Supervisor: Mgr. Klára Konečná, Ph.D. Background: The aim of this thesis, due to the growing incidence of fungal diseases and the growing incidence of resistance, was to determine the activity of potentially antimycotic active substances. We tested newly synthesized compoused, structurally based on the substance of pyrazinamide which is significant antituberculotic. Methods: Testing of substances was carried out using a broth microdilution method on eight strains of pathogenic fungi consisting of five yeast strains: Candida albicans, Candida tropicalis, Candida krusei, Candida glabrata, Trichosporon asahii and three strains of filamentous fungi: Aspergillus fumigatus, Absidia corymbifera, Trichophyton mentagrophytes. Results: From the range of tested concentrations and from the total number of the thirty tested substances, the most noticeable antifungal aktivity was revealed in the substance of 5-methyl-6-(2-phenylhydrazinyl)pyrazine-2,3- dicarbonitrile. All strains, except Trichophyton mentagrophytes strain, showed a relatively...

Charles University Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Study program: Specialist in Laboratory Methods Candidate: Bc. Aneta Janků Supervisor: PharmDr. Ondřej Janďourek, Ph.D. Title of diploma thesis: In vitro screening of novel potentially active antimycotic compounds III Key words: yeasts, moulds, antimycotics, mechanism of action of polyenes, microdilution broth method, MIC - minimal inhibition concentration. The main topic of this diploma thesis is in vitro screening of new, potentially active antifungal compounds. The introductory chapter in the theoretical part of the work is devoted to the epidemiology of fungal infections. The classification of micromycetes and the characteristics of the fungal eukaryotic cell are given below, focusing on composition of the plasma membrane and the cell wall. A separate chapter also deals with specific species of fungi and the diseases they cause. The main topic is drugs from the group of antifungals, where more attention is focused on polyene antifungals, their mechanism of action in detail and the emergence of resistance. An integral part are also the stages of development of new drugs and a list of novels developing antifungals. The final chapter describes the types of methods designed for in vitro evaluation...

Bei 85 Patienten (61 % Männer, 39 % Frauen, Altersmedian: 49 Jahre) nach Leber- (38), Herz- (34) und Lungentransplantation (13) wurde die orale Besiedlung mit Candida-Spezies und deren Biotypen sowie klinische Manifestationen einer Candidiasis bestimmt. Eine orale Candidiasis wurde bei 21/85 Patienten (24,7 %) diagnostiziert (pseudomembranöse Form: 15,3 %; erythematöse Form: 9,4 %; Cheilitis angularis: 3,5 %). Bei 63/85 Patienten (74,1%) wurden Candida spp. nachgewiesen. Von allen gefundenen Candida-Isolaten war C. albicans die am häufigsten isolierte Spezies (73 %), gefolgt von C. glabrata, C. krusei und C. famata (9,5 %; 6,3 %; 3,2 %). Außerdem wurden C. lusitaniae, C. guilliermondii, C. kefyr, C. magnoliae, Pichia ohmeri und C. dubliniensis, eine Spezies, die anfänglich nur bei HIV-positiven Individuen auftrat, identifiziert. Für C. albicans konnten sieben Biotypen nachgewiesen werden. Eine Korrelation der klinischen Manifestationen der Candidiasis und der identifizierten Spezies bzw. Biotypen konnte nicht gefunden werden. Während bei Patienten ohne Antimykotikatherapie neben C. albicans (87 %) nur drei verschiedene non-albicans-Spezies (C. glabrata: 8%; C. dubliniensis: 3 % und C. famata 3 %) identifiziert wurden, konnten bei Patienten mit Antimykotikatherapie sieben verschiedene non-albicans-Spezies nachgewiesen werden. C. albicans wurde nur noch zu 50 %, andere Spezies, wie C. krusei und C. glabrata, jedoch vermehrt identifiziert (C. krusei: 17 %; C. glabrata: 13 %; C. famata, C. guilliermondii, C. kefyr, C. lusitaniae C. magnoliae: 4 %). Die vorliegende Studie weist darauf hin, dass eine Dauertherapie bzw. notwendig verbreitete prophylaktische Gabe von Antimykotika (Amphotericin B; Fluconazol/Itraconazol) das Auftreten von non-albicans-Spezies fördert. Resistenzentwicklung und das Auftreten bisher apathogener Spezies und Biotypen spielen bei Patienten nach Organtransplantation eine bedeutende Rolle. / For evaluation of Candida carriage, oral swabs were taken from the tongue of 85 patients after liver- (38), heart- (34) and lung transplantation (13) (61 % men, 39 % women, median age: 49 years). Oral candidiasis was found in 21/85 patients (24,7 %) (pseudomembranous form: 15,3 %; erythematous form: 9,4 %; angular cheilitis: 3,5 %). Candida species were cultured in 63/85 patients (74,1 %). C. albicans was the most common isolate (73 %), followed by C. glabrata, C. krusei and C. famata (9,5 %; 6,3 %; 3,2 %). Other isolated species were C. lusitaniae, C. guilliermondii, C. kefyr, C. magnoliae, Pichia ohmeri and C. dubliniensis, the latter being a species first described in oral cavities of HIV-infected individuals. According to the API 20C AUX assimilation profiles seven different phenotypes were identified. No correlation was seen between clinical features and isolated species or biotypes. In patients without antimycotic therapy four different Candida species (C. albicans: 87 %; C. glabrata: 8 %; C. dubliniensis: 3 % and C. famata: 3 %) were identified, whereas, in patients with antifungal therapy eight different Candida species (C. famata, C. guilliermondii, C. kefyr, C. lusitaniae C. magnoliae: 4 %) were isolated. In only 50 % of the latter group C. albicans was detected, while C. glabrata in 17 % and C. krusei in 13 % were identified Long-term therapy and prophylaxis with antifungal agents (amphotericin B; fluconazole/itraconazole) to suppress fungal infections in immunosuppressed patients have contributed to a significant increase in non-albicans-infections because of the high incidence of resistance of the species to these drugs. On the other hand, risk of infection caused by less virulent species is increasing.

No description available.