Made available in DSpace on 2015-06-17T19:33:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-07-11. Added 1 bitstream(s) on 2015-06-18T12:48:23Z : No. of bitstreams: 1 000832029.pdf: 1345027 bytes, checksum: 6207079d0ab94cde1a6d3a7db40846f6 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Paracoccidiodomicose (PCM) é uma micose sistêmica endêmica na América Latina, de alta prevalência no Brasil, que tem como agente etiológico os fungos dimórficos do gênero Paracoccidioides, P. brasiliensis e P. lutzii. No processo de infecção as adesinas, substâncias sintetizadas por estes fungos que se ligam a matriz extracelular, são importantes fatores de virulência para o estabelecimento da infecção. A proteína de 30kDa, pertencente a família de proteínas 14-3-3, se destaca no processo adesivo deste fungo. As proteínas 14-3-3 são uma família de proteínas presentes em todas as células eucariotas e possuem múltiplas funções. Em P. brasiliensis, a proteína 14-3-3Pb, liga-se a laminina, principal componente da matriz extracelular das células hospedeiras, e durante a infecção sua expressão é aumentada. Com o intuito de compreender melhor a função desta proteína o objetivo deste estudo foi realizar a análise funcional da 14-3-3Pb através da obtenção de um homólogo funcional em S. cerevisiae e análise do anticorpo monoclonal anti-14-3-3Pb. S. cerevisiae foi escolhida como modelo de estudo por ser uma levedura amplamente utilizada na pesquisa genética, ao contrário de P. brasiliensis, e por possuir duas isoformas de 14-3-3, Bmh1p e Bmh2p, com alta identidade com 14-3-3Pb Para obtenção do homólogo funcional, foi realizada a transformação do vetor pYES-14-3-3Pb em S. cerevisiae. A partir da obtenção dos transformantes a avaliação da complementação foi realizada e foi observado uma complementação parcial das proteínas Bmh1p e Bmh2p por 14-3-3Pb. Ainda foram realizados teste de sensibilidade aos antifúngicos e a derivados semissintéticos do ácido gálico, onde foi possível observar um aumento da sensibilidade das linhagens com nocaute para os genes BMH1 e BMH2, S. cerevisiae Δbmh1 e Δbmh2, quando comparado à linhagem selvagem. A análise do anticorpo monoclonal foi realizada através de ensaio... / Paracoccidioidomycosis (PCM) a systemic mycosis endemic in Latin America, with high prevalence in Brazil, has as etiological agent dimorphic fungi Paracoccidioides spp., P. brasiliensis e P. lutzii. During the infection process the adhesins, substances synthetized by fungi that interacts with host's extracellular matrix (ECM), are important virulence factors for the establishment of infection. A 30kDa protein that belongs to 14-3-3 proteins family stands out in the adhesion process of this fungus. The 14-3-3 proteins are present in all eukaryotic cells and play multiple functions. In P. brasiliensis, the 14-3-3Pb protein binds to lamin, the major component of ECM from host cells, and during the infection the expression is increased. In order to have a better understanding of 14-3-3Pb functions the aim of this study is to perform a functional analysis of this protein through achieving a functional homologous in S. cerevisiae and to analyze the monoclonal antibody anti-14-3-3Pb during infection. S. cerevisiae was chosen as model because it's widely use in genetic research, unlike P. brasiliensis, and has two isoforms of 14-3-3 proteins, Bmh1p and Bmh2p, with high identity with 14-3-3Pb. The functional homologous were obtained by yeast transformation of pYES-14-3-3Pb vector. Complementation assay was performed with obtained transformants, and it was observed that 14-3-3Pb partially complements Bmh1p and Bmh2p, with higher complementation of Bmh2p. Also susceptibility assays were performed with antifungal drugs and semi-synthetic compounds derived from gallic acid where it was observed that S. cerevisiae wild type was less sensitive to antifungals than the knockout strains, S. cerevisiae Δbmh1 and Δbmh2. Monoclonal antibody anti14-3-3Pb was evaluated alone and in association with substances with antifungal activities through inhibition adhesion assay, where it was observed that the anti-14-3-3Pb alone is able to inhibit P. brasiliensis ...

Resumo: O fungo termo dimórfico, Paracoccidioides brasiliensis é o agente etiológico da Paracoccidioidomicose (PCM), a micose sistêmica mais prevalente da América Latina. Este fungo vem sendo frequentemente isolado de amostras clínicas, tecidos de tatu (Dasypus novemcinctus) e recentemente foi também isolado de cão. Este trabalho avaliou a transição de micélio para levedura (M-L), a termo tolerância e o perfil de virulência em nove isolados de P. brasiliensis (quatro de pacientes humanos, quatro de tatus e um de cão), bem como a sua relação com a seqüência parcial e expressão do gene hsp70 (Heat Shock Protein 70) através de Real Time RT-PCR. Tanto os dados morfológicos como moleculares se mostraram variáveis dentre os diferentes isolados. Alguns destes dados, como sequenciamento e morfologia leveduriforme corroboram com a divisão de nossos isolados nas duas espécies crípticas simpátricas previamente propostas por Matute et al (2006). Nossos resultados confirmam que a HSP70 pode ser um importante fator de virulência por estar associado à termo tolerância, mas sua expressão parece não ser diretamente associada a altos padrões de virulência. / Abstract: The thermo dimorphic fungus Paracoccidioides brasiliensis is the etiological agent of Paracoccidioidomycosis (PCM), the most prevalent systemic mycosis in Latin America. The previous phylogenetic species recognition proved the existence of, at least, three cryptic species in this pathogen. In this work we evaluated the mycelia to yeast (M-Y) transition, thermo tolerance and virulence profiles of nine isolates of P. brasiliensis, (including members of two of the three species) as well as its relation to the partial sequence and expression of hsp70 gene. It was observed a large phenotypic variability concerning the M-Y transition. The isolates Bt84 and T10 took more time to convert to the yeast form. These same isolates presented stretched yeast cells at 36°C, instead of the typical round cells. It was also observed arthroconidia production during the M-Y transition for some of the nine isolates studied. The hsp70 expression showed to be variable among our isolates. The partial sequencing of hsp70 gene resulted in a Neighbour Joining tree that divided our isolates in two main groups. Our data confirm that hsp70 gene might be an important virulence factor, associated with the thermo tolerance, but its expression does not seem to be directly related to high virulence profiles. We also presented some preliminary results about mycological characters that could be important candidates for morphologic markers for species recognition, as well as the partial sequencing of one member of the hsp70 gene family that allowed the separation of our isolates in two clusters, that correspond to the two sympatric cryptic species that occur in our PCM hyper endemic area (Botucatu, SP, Brazil). / Orientador: Eduardo Bagagli / Coorientador: Ivan de Godoy Maia / Banca: Everaldo dos Reis Marques / Banca: Maria Terezinha Serrão Peraçoli / Mestre

Resumo: A paracoccidioidomicose (PCM) é micose sistêmica causada pelos fungos dimórficos Paracoccidioides brasiliensis (espécies cripticas S1, PS2, PS3) e Paracoccidioides lutzii (Pb01-like espécies), endêmica na América Latina, principalmente no Brasil. A capacidade de causar micose com grande variedade de manifestações clínicas, desde formas localizadas até doença disseminada evoluindo para letalidade, depende da virulência do fungo e de sua habilidade em interagir com as estruturas superficiais do hospedeiro e invadi-las, e a resposta imunológica deste último. P. brasiliensis tem a capacidade de aderir e invadir células epiteliais de linhagens humanas e animais e o processo de invasão do fungo afeta a estrutura do citoesqueleto, interferindo em aspectos morfológicos da actina, tubulina e citoqueratina, indicando a participação funcional dos microfilamentos e microtúbulos neste mecanismo. Em estudos prévios foi identificada adesina de P. brasiliensis de 30 kDa, ligante de laminina, caracterizada como uma proteína pertencente à família 14-3-3. O objetivo deste trabalho foi produzir a proteína recombinante, verificar o papel desta na interação do fungo com células epiteliais pulmonares de linhagem contínua. Para tanto, com o anticorpo anti-14-3-3 foi verificada a sua localização, tanto nas formas leveduriformes do fungo como no processo de interação. A clonagem foi realizada em vetor de clonagem pCR2.1-TOPO - pET32a, para permitir a expressão da proteína Pb14-3-3r com cauda de histidina no espaço periplasmático de E. coli. A fração periplasmática foi purificada por cromatografia de afinidade seguida de eletroeluição. Foi possível verificar alteração do padrão de distribuição de actina quando as células foram tratadas com a proteína recombinante e nativa. A proteína 14-3-3 apresenta distribuição ubíqua na... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Paracoccidioidomycosis (PCM) is a systemic mycosis caused by the dimorphic fungus Paracoccidioides brasiliensis (cryptic species S1, PS2, PS3) and Paracoccidioides lutzii (Pb01-like species), endemic in Latin America, mainly Brazil. The ability to cause mycosis with a variety of clinical manifestations, from localized forms to disseminated disease progressing to lethality, possibly depends on the relationship between the virulence of these, the ability to interact with the surface structures of the host and invade them, and this immune response. P. brasiliensis has the ability to adhere and o invade human and animal epithelial cells lineage and the process of invasion of the fungus affects the structure of the cytoskeleton, morphological interfering with actin, tubulin and cytokeratin morphology, indicating the functional participation of microfilaments and microtubules in this mechanism. Previous study identified a 14-3-3 protein (30 kDa) that acts as a P. brasiliensis adhesin (laminin ligand) and this protein contributes to the virulence of this important fungal pathogen. The objective of this study was to produce recombinant protein, to verify the role of the interaction of the fungus with lung epithelial cells of continuous lineage. To do so, with the anti-14-3-3 was verified its location, both in the forms of the fungus and yeast in the process of interaction. The cloning was done in cloning vector pCR2.1-TOPO - pET32a to allow expression of protein Pb14-3-3r-tailed histidine periplasmic space of E. coli. The periplasmic fraction was purified by affinity chromatography followed by electroelution. It was possible to see change in the pattern of distribution of actin when cells were treated with recombinant and native protein. The 14-3-3 protein has ubiquitous distribution in yeast cells of P. brasiliensis (strain 18/S1) have a certain... (Complete abstract click electronic access below) / Orientador: Maria José Soares Mendes Giannini / Banca: Cleslei Fernando Zanelli / Banca: Alexandra Ivo de Medeiros / Banca: Clayton Luiz Borges / Banca: Oscar Zaragoza Hernandez / Doutor

Orientador: Eduardo Mello de Capitani / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-06T19:31:01Z (GMT). No. of bitstreams: 1 Cerqueira_ElzaMariaFigueirasPedreirade_M.pdf: 18712156 bytes, checksum: 7f2620dcabd247de06998a15e4784d3f (MD5) Previous issue date: 2006 / Resumo: O objetivo deste estudo foi avaliar as anormalidades torácicas na fase ativa da forma clínica crônica de paracoccidioidomicose através da tomografia computadorizada de alta resolução. Trinta e três pacientes (31 homens, 2 mulheres), com idade entre 32 e 69 anos, com diagnóstico confirmado de paracoccidioidomicose e em tratamento há menos de 30 dias, realizaram tomografia computadorizada de alta resolução. Dois radiologistas determinaram o grau de profusão (ausente, discreto, moderado e acentuado) de 25 achados pulmonares, a distribuição dos achados nos eixos pulmonares vertical e horizontal e a presença de aprisionamento aéreo, espessamento pleural, derrame pleural e linfonodomegalias Os achados mais freqüentes foram vidro fosco (97%), espessamento do interstício interlobular (93,9%), nódulo (75,8%), cavidade (71,2%), enfisema (69,7%), linfonodomegalias (69,7%), pequenos nódulos centrolobulares (66,7%), espessamento intersticial peribroncovascular (63,6%), consolidação (57,6%), e distorção arquitetural (57,6%). Diferentes graus de profusão foram observados na maioria dos achados, e dentre os achados pulmonares mais freqüentemente observados apenas consolidação não apresentou grau de profusão acentuado Predominam as alterações pulmonares distribuídas difusamente no eixo vertical pulmonar, comprometendo indistintamente a região central e periférica, poupando as regiões anteriores dos campos inferiores, e com marcante predomínio posterior no campo inferior (78,8%). São diversos os achados observados na tomografia computadorizada de tórax de alta resolução na fase ativa da PCM, não sendo possível caracterizar um padrão tomográfico específico da doença. Estão presentes sinais de comprometimento alveolar e intersticial, nódulos e fibrose que se manifesta principalmente por distorção arquitetural e bronquiectasias e/ou bronquioloectasias de tração / Abstract: Our purpose is to evaluate the pulmonary abnormalities on high-resolution CT in the active phase of chronic clinical form of paracoccidioidomycosis.Thirty-three patients (31 men, 2 women) carrying a confirmed diagnosis of paracoccidioidomycosis and under less than 30 days of treatment, have been submitted to high-resolution chest CT. Twenty-five pulmonary high-resolution CT findings have been graduaded by a four-point scale (0 to 3). The grade of each pulmonary finding, their distribution into transverse and longitudinal axes, and the frequency of air-trapping, pleural thickening , pleural effusion, and lymph nodes enlargement have been determinated by two radiologists Findings present at more than 50% of the patients have been ground-glass opacity (97% of patients), interlobular interstitial thickening (93,9%), nodule (75,8%), cavitation (71,2%), emphysema (69,7%), lymph nodes enlargement (69,7%), small centrilobular nodules (66,7%), peribronchovascular interstitial thickening (63,6%), consolidation (57,6%), and architectural distortion (57,6%). The majority of findings have been presented in all three profusion grades (discrete, moderate and severe). Among those that have been observed at more than 50% of the patients, consolidation is the only, which has not been observed in severe grade of profusion The HRCT findings regarding anterior versus posterior predominance have shown more frequently an indifferent distribution in upper and middle lung fields, and more frequently posterior predominance in lower lung field (78,8%). No predominance regarding central versus peripheral distribution have been observed in the majority of the fields. No specific high-resolution CT pattern was found in the active phase of chronic clinical form of paracoccidioidomycosis. Findings related to alveolar and interstitial disease, nodules and fibrosis, represented mainly by architectural distortion and bronchiectasis and bronchiolectasis have been seen / Mestrado / Clinica Medica / Mestre em Clinica Medica

Study objectives: To study the epidemiologic and clinical features of blastomycosis in northeast Tennessee. Design: Retrospective review of blastomycosis cases in the region from 1980 through 1995. Setting: Hospitals located in the Tri-Cities region of northeast Tennessee. Patients: Seventy- two patients with confirmed blastomycosis infection. Interventions: None. Results: During the 1980 to 1995 study period, we documented 72 cases of blastomycosis. The mean age was 52 years (range, 13 to 86 years), most were male (69.4%), and nine were immunocompromised. A possible environmental exposure was noted for 28 patients. Pulmonary involvement represented the most common site of infection (61 cases), but multiorgan involvement was common (17 cases). Most patients with pulmonary blastomycosis (66%) presented with a chronic illness, and radiologic findings usually revealed local consolidation or a mass-like lesion. Nine patients developed ARDS with an associated mortality rate of 89%, compared with a 10% mortality for non-ARDS pulmonary cases. Antifungal treatment regimens varied widely, with amphotericin B often used for sicker patients. An epidemiologic evaluation revealed that the mean yearly incidence rate for blastomycosis quadrupled between 1980 and 1987 (0.31 cases/100,000 population) and 1988 to 1995 (1.23 cases/100,000 population) (p=0.00001). Most new blastomycosis cases in the 1988 to 1995 period occurred in three counties in the region where significant new construction projects have been underway. Conclusion: Blastomycosis is endemic in northeast Tennessee and the number of eases is increasing, coinciding with major new construction in the region. Clinicians in the area must be alert to this condition.

Espécies de Malassezia fazem parte da microbiota de humanos e de animais. Essas leveduras lipofílicas são microrganismos oportunistas que estão associados com muitas doenças superficiais como: pitiriase versicolor, dermatite seborréica, foliculite, dermatite atópica e algumas infecções sistêmicas. As espécies de Malassezia têm sido identificadas através de procedimentos morfológicos e bioquímicos, no entanto, pequenas semelhanças entre algumas espécies estão presentes em algumas regiões do genoma. Foi avaliado o PCR-RFLP, método molecular para genotipar espécies de Malassezia obtidas de 55 amostras clinicas isoladas. Foram analisados 23 pacientes com dermatite seborréica, pitiriase versicolor e com a síndrome de Gourgerot- Carteaud. Encontramos quatro espécies diferentes: M. furfur, M. globosa, M. sympodialis and M. slooffiae. A identificação fisiológica e o PCR-RFPL foram compatíveis em 83% das amostras. M. furfur esteve presente em 52% dos casos, o que sugere que é o agente causador da pitiriase versicolor e da dermatite seborréica. Os resultados sugerem que a utilização do PCR-RFLP em amostras clínicas é importante no diagnóstico de algumas micoses causadas por esta levedura. / Malassezia species are part of the microbiota of humans and other animals. These lipophilic yeasts are opportunistic microorganisms that are associated with some dermatoses including pityriasis versicolor, seborrheic dermatitis, folliculitis ptirospórica, atopic dermatitis, some systemic infections among others. The species of Malassezia have been identified by morphological and biochemical and molecular techniques currently. We identify the species of Malassezia obtained from 55 clinical samples and 15 samples that formed the control group, by conventional techniques using a medium with not described in the literature, the mixture of media and Dixon Kimming, which was higher than each when used separately. Used the molecular method of PCR-RFLP to genotype 23 of the 55 clinical samples of Malassezia spp. from patients with seborrheic dermatitis, pityriasis versicolor and Gourgerot - Carteaud syndrome. Could the isolation of four species: M. furfur, M. globosa, M. Sympodialis and M. slooffiae. The physiological identification obtained with the PCRRFLP was consistent in 83% of the samples. M. furfur was present in 52% of cases, suggesting that is the main causative agent of pityriasis versicolor and perhaps the agent most frequently found in seborrheic dermatitis. The results suggest that the use of PCR-RFLP method in clinical samples is of great use for the identification of Malassezia species associated with diseases in humans.

Com o objetivo de avaliar os linfócitos do sangue periférico na micose fungóide, foram realizados hemograma e imunofenotipagem por citometria de fluxo de 40 doentes e de 26 indivíduos saudáveis. Verificou-se que células de Sézary acima de 7% e linfócitos pleomórficos acima de 24% estiveram presentes apenas na doença. Alterações quantitativas, qualitativas, perda de marcadores imunofenotípicos e presença de populações linfocitárias com tamanhos distintos, na citometria, foram verificadas nos doentes mais precocemente que alterações numéricas e morfológicas do hemograma / Aiming to evaluate peripheral blood lymphocytes in mycosis fungoides, we have performed hemogram and immunophenotyping by flow cytometry in about 40 patients and 26 healthy people. We have noticed that only diseased patients presented Sézary cells higher than 7% and pleomorphic cells higher than 24%. Quantitative and qualitative changes, loss of immunophenotyping markers and the presence of lymphocytes populations with different size, on flow cytometry, were firstly verified on patients rather than numeric and morphologic changes in

Com o objetivo de avaliar os linfócitos do sangue periférico na micose fungóide, foram realizados hemograma e imunofenotipagem por citometria de fluxo de 40 doentes e de 26 indivíduos saudáveis. Verificou-se que células de Sézary acima de 7% e linfócitos pleomórficos acima de 24% estiveram presentes apenas na doença. Alterações quantitativas, qualitativas, perda de marcadores imunofenotípicos e presença de populações linfocitárias com tamanhos distintos, na citometria, foram verificadas nos doentes mais precocemente que alterações numéricas e morfológicas do hemograma / Aiming to evaluate peripheral blood lymphocytes in mycosis fungoides, we have performed hemogram and immunophenotyping by flow cytometry in about 40 patients and 26 healthy people. We have noticed that only diseased patients presented Sézary cells higher than 7% and pleomorphic cells higher than 24%. Quantitative and qualitative changes, loss of immunophenotyping markers and the presence of lymphocytes populations with different size, on flow cytometry, were firstly verified on patients rather than numeric and morphologic changes in

Espécies de Malassezia fazem parte da microbiota de humanos e de animais. Essas leveduras lipofílicas são microrganismos oportunistas que estão associados com muitas doenças superficiais como: pitiriase versicolor, dermatite seborréica, foliculite, dermatite atópica e algumas infecções sistêmicas. As espécies de Malassezia têm sido identificadas através de procedimentos morfológicos e bioquímicos, no entanto, pequenas semelhanças entre algumas espécies estão presentes em algumas regiões do genoma. Foi avaliado o PCR-RFLP, método molecular para genotipar espécies de Malassezia obtidas de 55 amostras clinicas isoladas. Foram analisados 23 pacientes com dermatite seborréica, pitiriase versicolor e com a síndrome de Gourgerot- Carteaud. Encontramos quatro espécies diferentes: M. furfur, M. globosa, M. sympodialis and M. slooffiae. A identificação fisiológica e o PCR-RFPL foram compatíveis em 83% das amostras. M. furfur esteve presente em 52% dos casos, o que sugere que é o agente causador da pitiriase versicolor e da dermatite seborréica. Os resultados sugerem que a utilização do PCR-RFLP em amostras clínicas é importante no diagnóstico de algumas micoses causadas por esta levedura. / Malassezia species are part of the microbiota of humans and other animals. These lipophilic yeasts are opportunistic microorganisms that are associated with some dermatoses including pityriasis versicolor, seborrheic dermatitis, folliculitis ptirospórica, atopic dermatitis, some systemic infections among others. The species of Malassezia have been identified by morphological and biochemical and molecular techniques currently. We identify the species of Malassezia obtained from 55 clinical samples and 15 samples that formed the control group, by conventional techniques using a medium with not described in the literature, the mixture of media and Dixon Kimming, which was higher than each when used separately. Used the molecular method of PCR-RFLP to genotype 23 of the 55 clinical samples of Malassezia spp. from patients with seborrheic dermatitis, pityriasis versicolor and Gourgerot - Carteaud syndrome. Could the isolation of four species: M. furfur, M. globosa, M. Sympodialis and M. slooffiae. The physiological identification obtained with the PCRRFLP was consistent in 83% of the samples. M. furfur was present in 52% of cases, suggesting that is the main causative agent of pityriasis versicolor and perhaps the agent most frequently found in seborrheic dermatitis. The results suggest that the use of PCR-RFLP method in clinical samples is of great use for the identification of Malassezia species associated with diseases in humans.

A paracoccidioidomicose é uma micose sistêmica caracterizada por ser uma doença granulomatosa. As formas benignas da doença são caracterizadas por uma infecção localizada, contendo granulomas compactos com poucos fungos; já nas formas mais graves, ocorre um processo granulomatoso frouxo com focos de necrose e intensa disseminação fúngica. Objetivou-se avaliar o desenvolvimento de lesões granulomatosas em baço, fígado, pulmão e epiplon de camundongos, após infecção pela via intraperitoneal com o isolado de alta virulência, Pb18, em diferentes períodos de infecção após tratamento com fármacos, os quais possuem mecanismo de ação relacionado com a alteração no balanço entre a síntese e degradação dos produtos do colágeno, interferindo diretamente na formação do granuloma A citocina IFN-<font face=\"Symbol\">g, o antibiótico Tetraciclina e as drogas antiinflamatórias Lumiracoxib e Celecoxib. Avaliamos a presença de alguns componentes do granuloma (colágeno, células do infiltrado inflamatório, de citocinas primordiais para sintese/degradação da MEC do granuloma, presença de P. brasiliensis). / Paracoccidioidomycosis (PCM) is a systemic mycosis that is endemic in Latin America, whose causative agent is the thermal dimorphic fungus Paracoccidioides brasiliensis (Pb). PCM is a granulomatous disease, and the formation of granulomas can be understood as a mechanism of the body to block and limit the invasiveness of the fungus or its antigenic components, once unable to lyse them. Bening forms of the disease are characterized by a localized infection, where granulomasa are compact and contain few fungi. More severe forms present loose granulomatous processes with foci of necrosis and severe fungal. Studies in which granulomatous response was developed in resistant (A/J) and susceptible (B10.A) mice to the high virulence isolate Pb18 showed the presence of different patterns of injuries related to the type of extracellular matrix (ECM) components and the different cells types in the area, suggesting a important role of these elements in the formation and constitution of the granuloma and thus the outcome of infection. In our project, we aimed to evaluate the development of granulomatous lesions in the spleen, liver, lung and omentum of mice susceptible to PCM after intraperitoneal infection with Pb18, at different periods of infection (acute and chronic) with or without treatment with drugs. These drugs have mechanisms of action closely related to the change in the balance between synthesis and degradation of collagen Thus, they interfere directly in the granuloma formation and in maintaining the viability of fungi and also with the development of fibrosis. Which is a common and devastating sequelae of numerous infections including the PCM, with the characteristic proliferation of fibroblasts and deposition of ECM. The treatments were chosen based on prior knowledge on their effects on the course of experimental murine PCM. IFN-<font face=\"Symbol\">g was chosen due to its antifibrotic effect, being an activator of macrophages in infection by P. brasiliensis and increasing the fungicidal effect of neutrophils. The antibiotic tetracycline was used because of its inhibitory effect on the synthesis of extracellular matrix, limiting antimicrobial activity and the ability of collagenase to degrade ECM. Finally, the antiinflammatory drugs Celecoxib and Lumiracoxib (inhibitors of the COX-2 enzyme) 11 were used because they cause an increase in the expression of collagen type III and type IV. We analyzed the components of the granuloma (collagen, inflammatory cells, cytokines essential for synthesis / degradation of the ECM of the granuloma, the presence of P. brasiliensis). Among the cytokines analyzed, we studied the importance of TNF-<font face=\"Symbol\">&#945 in the formation of granulomas and regulation of matrix metalloproteinases (MMP) synthesis and function. We analyzed TGF-<font face=\"Symbol\">b because it negatively modulate the secretion of nitric oxide by macrophages and promote the accumulation of ECM and is believed to be the central mediator of the process of fibrosis in several pathologies. IFN-<font face=\"Symbol\">g was studied because of its correlation to the preferential Th1 immune response in diseases and infectious processes of fungal and bacterial infections, and also because it modulates fibroblast function.