Submitted by Irene Nascimento (irene.kessia@ufpe.br) on 2016-08-18T18:50:03Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) TESECouto,FMMBIBLIOTECA.pdf: 2624941 bytes, checksum: bb7fcea419304e7ea3eff4866c1b56e8 (MD5) / Made available in DSpace on 2016-08-18T18:50:03Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) TESECouto,FMMBIBLIOTECA.pdf: 2624941 bytes, checksum: bb7fcea419304e7ea3eff4866c1b56e8 (MD5) Previous issue date: 2013-02-13 / CAPES / Fungemia, presença de fungos no sangue, tem incidência crescente nas últimas décadas, acarretando sério problema em pacientes hospitalizados, sobretudo com câncer. Novos compostos antifúngicos e antitumorais têm sido propostos para tratamento destas doenças. Assim, o propósito desta pesquisa foi diagnosticar e traçar dados epidemiológicos de fungemia, assim como avaliar a ação antifúngica e antitumoral de isoflavonas da soja (daidzeína e genisteína) e hidroxipiridonas (ciclopirox olamina e octopirox olamina). Foram analisadas amostras de sangue de pacientes internados em hospital universitário de Recife-PE, Brasil e realizado antifungigrama dos agentes etiológicos com fluconazol, anfotericina B, isoflavonas da soja e hidroxipiridonas. Ainda, as isoflavonas e hidroxipiridonas foram avaliadas quanto à citotoxicidade às células neoplásicas (pulmão, laringe e cólon) e a ação da octopirox olamina contra candidemia e tumor sarcoma 180 em análises experimentais. Oito casos de fungemia foram diagnosticados tendo Candida, Histoplasma, Trichosporon, Cryptococcus e um fungo demáceo como agentes etiológicos. A maioria dos pacientes pertencia a idade adulta, sexo masculino e eram portadores da síndrome da imunodeficiência adquirida. Nenhuma das isoflavonas apresentou atividade antifúngica, contudo, a genisteína foi efetiva para câncer de laringe. Em contrapartida, as hidroxipiridonas, sobretudo, octopirox olamina, apresentaram já em baixas concentrações, ação antifúngica e antitumoral in vitro e in vivo. Para tratamento de neoplasias associadas à candidemia, octopirox olamina pode ser uma alternativa promissora. / Fungemia, presence of fungi in the blood, has a rising incidence in recent decades, causing serious problem in hospitalized patients, especially cancer. New antifungal and antitumor compounds have been proposed for treating these diseases. Thus, the purpose of this research was to diagnose and trace epidemiological data fungemia as well as evaluate the antifungal and antitumour of soy isoflavones (daidzein and genistein) and hydroxypyridones (ciclopirox olamine and octopirox olamine). We analyzed blood samples from patients admitted to a university hospital in Recife-PE, Brazil and performed in vitro the antifungal susceptibility of the etiologic agent fluconazole, amphotericin B, and soy isoflavones hydroxypyridones. Still, isoflavones and hydroxypyridones were evaluated for cytotoxicity to tumor cells (lung, larynx and colon) and the action of candidemia and octopirox olamine against sarcoma 180 tumor in experimental analyzes. Were diagnosed eight cases of fungemia with Candida, Histoplasma, Trichosporon, Cryptococcus and a dematiaceous fungus as etiological agents. Most patients belonged to adulthood, males and were carriers of acquired immunodeficiency syndrome. None of isoflavones showed antifungal activity, however, genistein was effective for larynx cancer. In contrast, hydroxypyridones especially octopirox olamine in already at low concentrations has antifungal and antitumor in vitro and in vivo. For treatment of malignancies associated with candidemia, octopirox olamine may be a promising alternative.

Invasive Pilzinfektionen stellen ein großes Problem bei Transplantatempfängern dar. Candida und Aspergillus spp. sind die häufigsten pathogenen Pilze bei Patienten nach KMT und Organtransplantationen. Diese Infektionen sind durch eine hohe Morbidität und Mortalität gekennzeichnet, insbesondere bei Patienten mit persistierender Granulozytopenie und damit jene nach allogener KMT. Die Mortalitätsrate kann durch eine Frühdiagnostik und durch Gabe einer geeigneten Therapie wesentlich reduziert werden. Die Symptome und Zeichen einer systemischen Pilzinfektion sind bei Transplantatempfängern untypisch. Die serologische Diagnostik von invasiven Candidosen oder Aspergillosen stellt eine zusätzliche Möglichkeit zur klinischen Untersuchung und anderen diagnostischen Maßnahmen dar. Diese Untersuchung umfasste 252 Patienten (17 Patienten nach KMT) und 235 Patienten von Intensivtherapiestationen (z. B. nach Organtransplantationen) in den Jahren 1991-1994 von der Humboldt-Universität zu Berlin (Charite). Die Patientenseren wurden routinemäßig auf das Vorkommen einer Candida- und Aspergillus Antigenämie geprüft. Zum Nachweis von zirkulierendem Galactomannan wurde ein Latex Agglutinationstest- Pastorex Candida und Aspergillus, Sanofi Diagnostics Pasteur, genutzt. Invasive Aspergillus-Pilzinfektionen wurden bei acht von 235 Patienten unter Intensivtherapie gefunden. Alle acht Patienten mit invasiver Aspergillose hatten einen positiven Aspergillus-Antigen-Test. Der direkte Nachweis von Antigenbestandteilen von Candida oder Aspergillus spp. erwies sich als vielversprechender frühdiagnostischer Test bei kritisch kranken und immunsupprimierten Patienten. / Invasive fungal infections are a major problem in transplant recipients. Candida and Aspergillus spp. are the most common fungal pathogens causing infection in patients undergoing BMT or solid organ transplantation. These infections are characterised by high morbidity and mortality, especially in patients with persistent granulocytopenia and in these receiving allogeneic bone marrow transplant. The mortality rate can be substantially reduced if an early diagnosis is made and the proper therapy given. The symptoms and signs of deep fungal infection in the transplant recipients are unreliable and often absent regardless of the type of organism or the site of infection. Laboratory tests are essential to establish the diagnosis of invasive fungal infection. The serological diagnosis of invasive candidosis or aspergillosis is at best an adjunct to clinical evaluation and other diagnostic procedures. The study comprises 252 patients undergoing allogeneic bone marrow transplantation (17 patients) and 235 patients from intensive care units (for instance after solid organ transplantation) in the years 1991-1994 at the Humboldt-University of Berlin (Charité). The serum of the patients were routinely screened for the occurrence of Candida and Aspergillus antigenemia (circulating galactomannan was detected using a latex agglutination test-Pastorex Candida and Aspergillus, Sanofi Diagnostics Pasteur). Invasive Aspergillus fungal infection was found in eight of the 235 intensive care patients. All these eight patients with invasive aspergillosis had an positive Aspergillus antigen test. The direct detection of antigenic components of Aspergillus and Candida spp. in serum appears promising as an early diagnostic test in critical ill and immunocompromised patients.

Aspergillus is a speciose genus encompassing nearly 400 species that has significant economic impacts on human health, the food industry, biotechnology and pharmacology. The research included in this thesis focuses on current issues related to the generic concept, subgeneric classification and species delimitation in Aspergillus. It addresses the need for revisions of several sections or species complexes. It provides novel information regarding etiology of aspergillosis as well as the antifungal susceptibilities of several less common opportunistic pathogens. The taxonomic section of the thesis contributes to the taxonomic stability and the new concept of the genus Aspergillus, which changed in response to the discontinuation of dual nomenclature in fungi. Sufficient arguments were collected (e.g., verification of monophyly, unifying phenotypic characters) for maintaining a broad concept of the genus and avoiding splitting it into several genera. All genera typified by sexual morphs and having Aspergillus asexual states were synonymized with Aspergillus and the appropriate names adopted; new combinations were made for teleomorphic species that lacked Aspergillus names. This thesis also contributed to infrageneric taxonomy of the genus via the proposal of four new sections in the subg. Circumdati,...