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Dissertação Acesso aberto (Open Access) Determinação das concentrações plasmáticas e teciduais de itraconazol em pacientes com cromoblastomicose(Universidade Federal do Pará, 2008-09-01) GRISÓLIA, Daniella Paternostro de Araújo; VIEIRA, José Luiz Fernandes; http://lattes.cnpq.br/2739079559531098Chromoblastomycosis is a subcutaneous mycosis caused by deployment transcutaneous of several species of dematiaceous fungi, that is, melanized fungi. Considering the incidence of this disease in the state of Pará and the resulting morbidity of patients affected, with economic and social repercussions, it was made to the optimization of therapeutic schemes adopted, to the best knowledge of the relation dose x response. The itraconazole is one of the few drugs available for treatment, which has marked variability kinetic intra and inter individual, which compromises the establishment of the relation dose and response, as well as tissue and plasma concentrations achieved. In this sense, this work aimed at validation of analytical methodology by High Performance Liquid Chromatography and subsequent determination of itraconazole in samples of plasma and tissue in 20 patients with chromoblastomycosis, assisted in the laboratory of dermatoimmunology Dr. Marcello Candia, Marituba, Pará, who used the drug in doses of 200mg/day and 400mg/day. The technique employed was validated and proved adequate results in accordance with applicable law. Concentrations of plasma and tissue of itraconazole in the dose of 200mg/day were 121.3 87.9 ng/mL and 5.36 5.9 μg/g. The average plasma concentration of itraconazole in patients using 400mg/day was 290 234 ng/mL, and the plasma and tissue mean concentrations of itraconazole in patients who showed no clinical favourable, at doses of 200mg, making it necessary to increase to 400mg were 217 216 and 304 173 ng/mL; 14.87 12.94 e 21.80 6.62 μg/g. The average of relation between tissue and plasma concentrations in patients who had positive developments in clinical in the doses of 200mg/day was 44.29 67.12 and those that did not show positive developments in clinical in the doses of 200mg/day, making necessary to increase to 400mg/day were 68.52 59.90 and 71.71 38.26 respectively.Tese Acesso aberto (Open Access) Estudo do Paracoccidioides brasiliensis no município de Buriticupu, Amazônia maranhense(Universidade Federal do Pará, 2010-10-01) CALVET, Clélea de Oliveira; ISHAK, Ricardo; http://lattes.cnpq.br/5621101706909450The objective of this study was to verify the presence of Paracoccidioides brasiliensis in the municipality of Buriticupu, located in the Amazon Maranhense. Intradermics tests were conducted with paracoccidioidine in 491 individuals, with 60 intradermics positive to the antigen. There was no statistically significant difference in the sample in relation to the positive test and the variables gender, socio culturals habits and level of education, although describe, the female has been the most frequent, totaling 33 patients, and that positive - reagents have habits that provide contact with the pathogen, and it was found to be the prevailing levels of schooling illiteracy (18 tested) and 1 st degree incomplete (26 tested). Fifty-one patients testing positive for intradermics to paracoccidoidine (85%) were the natural state of Maranhão. In reviewing the clinical data and laboratory records in general of the six patients diagnosed with the disease paracoccidioidomycosis, found that all were farmers with more than 10 years of residence in Buriticupu, with the presence of the fungus in the oral mucosa scraped the colouring of PAS and Gomori - Groccot, except for two patients: one with 36 months of treatment and another with 12 months of therapy, and without injury initial oral or later, both without reports of abandonment of treatment. We, therefore, that the exfoliative cytology is an easy way and low cost in aid of therapeutic control of patients.Dissertação Acesso aberto (Open Access) Imunoexpressão para CD1a em lesões cutâneas na doença de Jorge Lobo(Universidade Federal do Pará, 2009) UNGER, Deborah Aben-Athar; BRITO, Arival Cardoso de; http://lattes.cnpq.br/0563291980190339Jorge Lobo’s disease (DJL) is a chronic infection caused by the fungus Lacazia loboi, endemic in South America, especially in the Brazilian Amazon region. The most common clinical presentation is parakeloidal lesion located mainly in the lower limbs in men who practice agricultural activity. The fungus can be identified by both mycological and anatomopathological examination. The main objective of this study was to investigate the possible role of Langerhans' cells (LC) in the pathogenesis of the disease in tissue samples from skin lesions, using immunohistochemical technique. Thirty-three medical records were selected with their respective paraffin blocks of skin biopsies from patients with DJL (group 1) registered in the dermatology service at the Federal University of Para in the period from 1955 to 2005. The control group consisted of 10 paraffin blocks from normal skin (group 2) and 42 blocks from patients with paracoccidioidomycosis (PCM) (Group 3). In the analysis of patient medical records data were collected regarding age, sex, origin, profession, location and clinical type of the lesions. Langerhans cells were identified by immunohistochemistry using anti-CD1a antibody (Serotec). Patients were mostly men (84, 8%), farmers (72. 7%) aged between 46-65 years, with predominance of parakeloidal lesions (81. 8%) in the lower limbs (45. 5%). The number of positive cells was statistically analyzed. The LC were visualized along the epidermis in all biopsies from Jorge Lobo's disease. The morphology and the number of cells, did not differ from normal skin (p> 0. 05), and was increased when compared to the PCM lesions (p <0. 05). Langerhans cells were present in Jorge Lobo’s disease skin lesions similarly to the way they are in normal skin, not suffering any numerical or morphological alterations, unlike what occurred in PCM. These results suggest that in DJL fungi probably present some escape mechanism of the local immune system to evade the antigen presentation by Langerhans’ cells.Tese Acesso aberto (Open Access) Imunopatogenia da interação entre acrófagos e/ou células de Langerhans e Lacazia loboi(Universidade Federal do Pará, 2014-04-24) YAMANO, Suellen Sirleide Pereira; SALGADO, Claudio Guedes; http://lattes.cnpq.br/2310734509396125Lobomycosis is a chronic, granulomatous, fungal infection of the skin and subcutaneous caused by the fungus Lacazia loboi. This mycosis occurs predominantly in Amazon region and affect all populations groups. Histologically, there is a chronic inflammatory reaction characterized by the intense fibroplastia and histiocytosis, abundant number of macrophages, multinucleated giant cells and presence of large numbers of yeast. Macrophages are phagocytic cells that participate in the recognition and response to pathogens through phagocytosis, antigen presentation to T lymphocytes and cytokine production. Langerhans cells (LC) are a group of dendritic cells (DC) derived from bone marrow, which are located mainly in the suprabasal layer of the epidermis. Studies on hostfungal interaction in Jorge Lobo's disease are scarce. Therefore, this study constitutes an important step towards a better understanding of L. loboi biology and pathogenesis, enabling in vitro culture of this organism endemic in Amazon region and study of their antigenic properties, as well as new therapeutic approaches. The objective of this study was to analyze the in vitro interaction between non-activated peritoneal macrophages and/or Langerhans cells isolated from BALB/c mice and L. loboi, calculating infection, phagocytosis and cellular fusion rates; also measuring the production of TNF, IL-4, IL-6, IL-10 and IL-12. Results showed that L. loboi is phagocytosed by macrophages but not by LC. Phagocytosis and infection rates in the interaction between macrophages and L. loboi was similar to interaction between macrophages, Langerhans cells and L. loboi at all times analyzed. The mean number of yeast cell per macrophage was almost equal among interactions and over time, with mean variation from 1.2 to 1.6 yeast/macrophages. No giant cells formation in coculture studied. No significant difference occurred in IL-4, Il-2 and IL-10 production between interactions studied. TNF levels decrease in interaction between macrophages and L. loboi while adding LC induces increased production of TNF-α, especially after 48 hours. LC negatively modulate IL-6 production by macrophage and L. loboi also inhibits this production by macrophages alone or cocultured with LC. L. loboi stimulated significantly IL-12 production by macrophages co-cultured with LC, but not for LC alone or macrophages.Tese Acesso aberto (Open Access) Indução de escleróticas in vitro e análise da resposta imune dos pacientes de cromoblastomicose em tratamento com itraconazol(Universidade Federal do Pará, 2009-06-26) SILVA, Moisés Batista da; SALGADO, Claudio Guedes; http://lattes.cnpq.br/2310734509396125Chromoblastomycosis (CBM) is a chronic fungal disease witch affects the skin, characterized for slowing development of polymorphic skin, that present infiltrated inflammatory granulomatous in the presence of sclerotics cells, characteristic of this illness. One of the objectives of this study was to evaluate the induction of scleroticts cells for natural mediums, with biomasses of Bactris gasipaes and Theobroma grandiflorum, whose respective species had induced in vitro similar sclerotics cells to those found in tissue of patients, in 10 and 2 days, respectively, what it made possible the production of a powder medium inductor, already donated to other groups that study the CBM. Another objective was to evaluate the histopathology of the CBM in the patients, before and during the use of itraconazole (ITZ). For this, the technique of ELISA for the cytokines was used TNF-α, circulating IL-4 and IL-10, and the immunohistochemestry of biópsias in different times of treatment - that it allowed to analyze the quantitative and qualitative alterations of the cellular types during 12 months of the treatment with ITZ in the 200 dose of mg/dia - with antibodies anti- CD20, anti-CD8 and anti-CD68. How much the cytokines, the circulating IL-10 did not show significant change, while IL-4 and TNF-α had presented an increase of the levels throughout 12 months of treatment. In relation to the immunophenotyping, it had a significant reduction in the inflammatory process and the cellular infiltrated during 3 and 6 months of the treatment, whereas only to the 12 months had the significant regression of the number of sclerotics cells. The immunophenotyping disclosed that the macrophages are mainly located in the areas central areas of granuloma, whereas cells TCD8+ are in the periphery and cells TCD20+, which were found throughout the tissues, with a significant increase after 6 months of the treatment, returning to the initial levels after one year. The cytotoxic macrophages and lymphocytes were having presented a significant increase after 12 months of treatment with ITZ. These results demonstrate that the formation of granuloma in the CBM is similar to those observed in other granulomatous infectious disease, and that the presence of IL-4 and IL-10 can be related with the persistence of fungi in the injuries and with the difficulty of cure observed in these patients.Tese Acesso aberto (Open Access) Inquérito com paracoccidiodina em cinco cidades do Estado do Acre(Universidade Federal do Pará, 2011-09-30) FIGUEIREDO, Mediã Barbosa; ISHAK, Ricardo; http://lattes.cnpq.br/5621101706909450Paracoccidioidomycosis constitutes an important public health problem in Latin America. In Brazil, this disease is less frequent in North and Northeast regions, predominating the endemic areas in the Southeast. Despite the physiographic conditions of the North region favoring the development of Paracoccidioides brasiliensis, even so, the case reports are scarce. Perhaps this is due to the little consideration of deep mycoses about the differential diagnosis of chronic medical conditions, justified by the fact that the region is not considered endemic. With the objective of describing the prevalence of paracoccidioidomycosis in five cities of Acre, a cross-sectional population-based study was conducted, through a survey with the paracoccidioidin intradermal. The reading of the intradermal test was performed within 24 and 48 hours, being considered reactors the people with hardened areas of 5mm or more in diameter. Four hundred thirty-nine (439) people were studied and paracoccidiodomycosis-infection in the 48-hour reading was 41.2%. The findings of this study indicate that P. brasiliensis infection causes a considerable number of people in the study area to get infected, and therefore future clinical-epidemiological and mycological studies should better clarify the natural history of mycosis in this region.Tese Acesso aberto (Open Access) Isolamento e cultivo in vitro do agente etiológico da Doença de Jorge Lobo: morfologia, fisiologia e genoma de Candida loboi sp. nov(Universidade Federal do Pará, 2015-12-18) COSTA, Patricia Fagundes da; SALGADO, Claudio Guedes; http://lattes.cnpq.br/2310734509396125Jorge Lobo’s disease is a chronic granulomatous infection developing after traumatic implantation of the fungus in the skin. It presents with nodular, verrucous or keloid-like lesions mainly on legs and ears. The highest prevalence is at Amazon Region and it has been considered an emergent disease, presenting new cases on other continents in both, humans and dolphins. Little is known about L. loboi, and the absence of in vitro culture impairs the correct characterization of the fungus. This work had as the main goal to isolate, culture and characterize strains of the etiological agent of Jorge Lobo´s disease, obtained from patients attended at the Dr Marcello Candia Reference Unit in Sanitary Dermatology of the State of Pará, in Marituba, Pará, Brazil. During many years 23 patients were diagnosed and followed by our team. Most of them were male farmers, with age varying from 14 to 80 years-old. After biopsy of the lesion for confirming the diagnosis, the patients initiated treatment and the material was processed with dispase II at liquid medium RPMI, 37º C, 5% CO2 for 1-2 weeks to isolate yeast cells from human tissue. After 2-6 months in the medium, we observed fragmentation of mother cells and the presence of new yeast cells with diameter varying from 1 to 7μm. From that moment, it was possible to grow the strains in different liquid or solid mediums at 37º C or RT, where creamy, whitish cerebriform, sometimes hairy colonies were observed. Cells from those strains were analyzed by different techniques of optical and electron microscopy, biochemistry and genetics, ending with the description of the genome of one patient just after isolation of the fungal cells from the lesional skin, defining the following taxonomic identification: Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes; Saccharomycetales; Debaryomycetaceae; Candida/Lodderomyces clade; Candida; Candida sp. LDI48194. The peculiar clinical presentation associated to unique morphological, physiological and genetic characteristics that do not permit the definition of a known species indicate that the etiological agent of Jorge Lobo’s disease is a new species, for which we propose to use the name Candida loboi.Artigo de Periódico Acesso aberto (Open Access) Isolation of Fonsecaea pedrosoi from thorns of Mimosa pudica, a probable natural source of chromoblastomycosis(2004-02) SALGADO, Claudio Guedes; SILVA, Jorge Pereira da; DINIZ JUNIOR, José Antônio Picanço; SILVA, Moisés Batista da; COSTA, Patricia Fagundes da; TEIXEIRA, Cláudio Eduardo Corrêa; SALGADO, Ubirajara ImbiribaWe report the isolation of Fonsecaea pedrosoi from thorns of the plant Mimosa pudica L. at the place of infection identified by one of our patients. Clinical diagnosis of chromoblastomycosis was established by direct microscopic examination and cultures from the patient's lesion. The same species was isolated from the patient and from the plant. Scanning electron microscopy of the surface of the thorns showed the characteristic conidial arrangement of F. pedrosoi. These data indicate that M. pudica could be a natural source of infection for the fungus F. pedrosoi.Artigo de Periódico Acesso aberto (Open Access) Lacaziose (doença de Jorge Lobo): revisão e atualização(2007-10) BRITO, Arival Cardoso de; QUARESMA, Juarez Antônio SimõesLacaziosis, also known as Jorge Lobo s disease, lobomycosis and keloidal blastomycosis, is a chronic cutaneous and subcutaneous fungal granulomatous disease, caused by Lacazia loboi – an uncultivated fungal pathogen – characterized by the development of nodular keloidal lesions, particularly on the pinnae, face, upper and lower limbs, and with no involvement of mucous membranes. Most cases in humans were reported in South America, including the Caiabi Indians, in Central Brazil. The disease was described in non-human mammals, such as two species of dolphins (Tursiops truncatus and Sotalia guianensis) inhabiting the coasts of Florida (USA), South America (Suriname River estuary, Santa Catarina-Brazil coast) and Gulf of Gascony (Biscaya Bay, in Europe). The histopathological findings in dolphins were very similar to those observed in humans. The aspects related to the history, etiology, epidemiology and ecology, clinical manifestations, differential diagnosis, immunohistochemistry, pathology, ultrastructural, laboratory diagnosis and therapy of lacaziosis, are presented.Artigo de Periódico Acesso aberto (Open Access) Paracoccidioidomicose em crianças em Belém do Pará(1999-02) FONSECA, Eliane Regine de Souza da; PARDAL, Pedro Pereira de Oliveira; SEVERO, Luiz CarlosDuring the period from January/85 to July/96, 102 cases of paracoccidioidomycosis were observed in a hospital in Belém, PA. Thirteen of these cases were children between 3 and 13 years of age, with a predominance of females (8:5). All patients presented the disseminated subacute form of the mycosis. The high prevalence of the mycosis in children in endemic areas of the Amazon region is discussed.Artigo de Periódico Acesso aberto (Open Access) Primary endemic Cryptococcosis gattii by molecular type VGII in the state of Pará, Brazil(2008-12) SANTOS, Wallace Raimundo Araujo dos; MEYER, Wieland; COSTA, Solange do Perpétuo Socorro Evangelista; TRILLES, Luciana; NASCIMENTO, José Luiz Martins do; SOUSA, Rita Catarina Medeiros; MORALES, Bernardina Penarrieta; BEZERRA, Cláudia de Carvalho Falci; MACÊDO, Regina Célia Lima de; FERREIRA, Silvana O.; BARBOSA, Gláucia Gonçalves; PEREZ, Mauricio de Andrade; NISHIKAWA, Marília Martins; LAZÉRA, Márcia dos SantosIn order to study the infectious agents causing human disseminated cryptococcosis in the state of Pará, North Brazil, 56 isolates of Cryptococcusspp. (54 isolated from cerebral spinal fluid and two from blood cultures) from 43 cases diagnosed between 2003-2007 were analysed. The species were determined through morphological and physiological tests and genotypes were determined by URA5-RFLP and PCR-fingerprinting (wild-type phage M13). The following species and genotypes were identified: Cryptococcus neoformans VNI (28/56, 50%), Cryptococcus gattii VGII (25/56, 44.64%) and C. gattii VGI (3/56, 5.26%). The genotype VNI occurred in 12 out of 14 HIV-positive adults, whereas the genotype VGII occurred in 11 out of 21 HIV-negative adults (p < 0.02, OR = 6.6 IC95% 0.98-56.0). All patients less than 12 years old were HIV negative and six cases were caused by the VGII genotype, one by the VGI and one by VNI. Therefore, endemic primary mycosis in HIV-negative individuals, including an unexpectedly high number of children, caused by the VGII genotype deserves further study and suggests the need for surveillance on cryptococcal infection in the state of Pará, Eastern Amazon.Dissertação Acesso aberto (Open Access) Tinea Capitis: aspectos clínico-epidemiológicos e tratamento com terbinafina em crianças atendidas na localidade de Marituba-Pará-Brasil(Universidade Federal do Pará, 2003) TUMA, Kiânia Nazaré de Souza; SALGADO, Claudio Guedes; http://lattes.cnpq.br/2310734509396125Tinea capitis is an infectious disease that affects specially children and has as the main clinical features pruritus, scaling, breaking hairs and alopecia. Conventional treatment is based on the use of griseofulvine, a drug that needs to be used for a mean period of 45 days and have important adverse effects. In this prospective work, clinical and epidemiological aspects of tinea capitis in children living in Marituba, Pará, were analyzed. Furthermore, the efficacy of a 2-week regimen of terbinafine was analyzed. Among the main findings are: 1) the identification of the genera Trichophyton as the most prevalent in the cases of tinea capitis in this region, represented by the species Trichophyton tonsurans and Trichophyton rubrum; 2) the characterization of the clinical picture with pruritus, scalling, breaking hairs and alopecia, what is consistent with the literature; 3) the absence of a specific relation between the clinical picture and the etiologic agent found, what does not permit the diagnosis of the species only by the clinical picture; 4) the identification of antropophilic fungi as the etiologic agents, what indicates the possibility of interhumans transmission instead of animal-human transmission, besides the high levels of contact found between children and animais; and 5) the efficacy and safety of terbinafine, that is well tolerated and had a high healing rate of 94.11%, specially considering the fact that the predominant genera in the region of Marituba, Pará, is the Trichophyton. Therefore, the use of terbinafine in the patients diagnosed with tinea capitis in this region is an alternative to the use of griseofulvine.
