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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2007.tde-28012008-125448
Document
Author
Full name
Eriques Gonçalves da Silva
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2007
Supervisor
Committee
Campos, Mario Julio Avila
Cury, Arlete Emily
Gambale, Valderez
Pires, Maria de Fatima Costa
Rivera, Irma Nelly Gutierrez
Title in Portuguese
Avaliação da criptocococe experimental sistêmica em camundongos BALB/c e terapêutica com anfotericina B, fluconazol e associação.
Keywords in Portuguese
Cryptococcus neoformans
Anfotericina B
Associação terapêutica
Criptococose experimental
Fluconazol
Monoterapia.
Abstract in Portuguese
A criptococose clinica foi observada por volta do primeiro dia da inoculação e a sobrevida dos animais 15 dias após-inoculação (PI). Isolamos C. neoformans no cérebro a partir do 5º dia (PI) e no pulmão a partir 11º dia (PI). No 1º dia (PI) observamos por meio do tecido cerebral que já havia um quadro inicial de infecção, presença de edema, que evoluiu durante todo o período. C. neoformans foi visualizado primeiramente nos vasos capilares, o que nos leva a sugerir que seja esta rota importante para a entrada da levedura no órgão. A meningite aguda aconteceu por volta do 7º dia quando visualizamos o microrganismo na meninge e com um discreto infiltrado inflamatório. A partir do 13º dia a doença evoluiu para crônica permanecendo até o óbito dos animais. A monoterapia com anfotericina B (AMB) reduziu a sobrevida dos animais, enquanto que, o tratamento isolado com fluconazol (FLC) prolongou a mesma. A associação AMB-FLC foi eficaz, quando iniciamos o tratamento 24 horas (PI), enquanto que, o mesmo tratamento iniciado a partir do 7º dia quando já tínhamos um quadro compatível de meningite aguda não foi satisfatório. É importante ressaltar que os resultados descritos foram referentes à inoculação com isolado sensível in vitro ao fluconazol, enquanto que, o tratamento não resultou em êxito quando empregamos isolado resistente in vitro ao fluconazol.
Title in English
Evaluation of experimental systemic cryptococcosis in BALB/c mice, and its treatment with amphotericin B and fluconazole, alone and in association.
Keywords in English
Cryptococcus neoformans
Amphotericin B
Experimental cryptococcosis
Fluconazole
Monotherapy
Therapêutic association
Abstract in English
Clinical cryptococcosis was observed on day 1 postinoculation (PI), and the animals survived until day 15 PI. C. neoformans was isolated from brain tissue starting on day 5 PI, and from lung tissue starting on day 11 PI. On day 1 PI, signs of infection were already observed in brain tissue, with presence of edema, which evolved throughout the period. C. neoformans was first seen in the capillaries, suggesting that this is an important route for the entrance of the yeast into this organ. Acute meningitis occurred around day 7 PI, when the microorganism was observed in the meninges, along with a discrete inflammatory infiltrate. From day 13 PI onward the disease became chronic, persisting until the death of the animals. Treatment with amphotericin B (AMB) alone shortened the animals' survival, while treatment with fluconazole (FLC) alone lengthened it. Treatment with the two drugs in association was effective when treatment was begun at 24 hours PI, however, when treatment was begun at day 7 PI, already with signs of acute meningitis, the effectiveness was unsatisfactory. It is important to emphasize that these results relate to inoculation with an isolate susceptible in vitro to fluconazole, while the treatment was not effective for an isolate resistant in vitro to fluconazole.
 
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Publishing Date
2008-02-13
 
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