RESUMO

Paracoccidioidomycosis (PCM) is a systemic mycosis caused by thermally dimorphic fungi of the genus Paracoccidioides that affects predominantly 30-60-year-old male rural workers. The main clinical forms of the disease are acute/subacute, chronic (CF); almost all CF patients develop pulmonary fibrosis, and they also exhibit emphysema due to smoke. An important cytokine in this context, IL-1ß, different from the others, is produced by an intracellular multimolecular complex called inflammasome that is activated by pathogens and/or host signs of damage. Inflammasome has been recognized for its contribution to chronic inflammatory diseases, from that, we hypothesized that this activation could be involved in paracoccidioidomycosis, contributing to chronic inflammation. While inflammasome activation has been demonstrated in experimental models of Paracoccidioides brasiliensis infection, no information is available in patients, leading us to investigate the participation of NLRP3-inflammasome machinery in CF/PCM patients from a Brazilian endemic area. Our findings showed increased priming in mRNA levels of NLRP3 inflammasome genes by monocytes of PCM patients in vitro than healthy controls. Similar intracellular protein expression of NLRP3, CASP-1, ASC, and IL-1ß were also observed in freshly isolated monocytes of PCM patients and smoker controls. Increased expression of NLRP3 and ASC was observed in monocytes from PCM patients under hypoxia in comparison with smoker controls. For the first time, we showed that primed monocytes of CF-PCM patients were associated with enhanced expression of components of NLRP3-inflammasome due to smoke. Also, hypoxemia boosted this machinery. These findings reinforce the systemic low-grade inflammation activation observed in PCM during and after treatment.

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RESUMO

Paracoccidioidomycosis (PCM) is a systemic mycosis caused by thermally dimorphic fungi of the genus Paracoccidioides that affects predominantly 30-60-year-old male rural workers. The main clinical forms of the disease are acute/subacute, chronic (CF); almost all CF patients develop pulmonary fibrosis, and they also exhibit emphysema due to smoke. An important cytokine in this context, IL-1ß, different from the others, is produced by an intracellular multimolecular complex called inflammasome that is activated by pathogens and/or host signs of damage. Inflammasome has been recognized for its contribution to chronic inflammatory diseases, from that, we hypothesized that this activation could be involved in paracoccidioidomycosis, contributing to chronic inflammation. While inflammasome activation has been demonstrated in experimental models of Paracoccidioides brasiliensis infection, no information is available in patients, leading us to investigate the participation of NLRP3-inflammasome machinery in CF/PCM patients from a Brazilian endemic area. Our findings showed increased priming in mRNA levels of NLRP3 inflammasome genes by monocytes of PCM patients in vitro than healthy controls. Similar intracellular protein expression of NLRP3, CASP-1, ASC, and IL-1ß were also observed in freshly isolated monocytes of PCM patients and smoker controls. Increased expression of NLRP3 and ASC was observed in monocytes from PCM patients under hypoxia in comparison with smoker controls. For the first time, we showed that primed monocytes of CF-PCM patients were associated with enhanced expression of components of NLRP3-inflammasome due to smoke. Also, hypoxemia boosted this machinery. These findings reinforce the systemic low-grade inflammation activation observed in PCM during and after treatment.

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PURPOSE: To obtain a decellularized tracheal scaffold associating traditional approaches with the novel light-emitting diode (LED) proposal. METHODS: This study was performed with New Zealand adult rabbits weighing 3.0 - 4.0 kg. Different protocols (22) were used combining physical (agitation and LED irradiation), chemical (SDS and Triton X-100 detergents), and enzymatic methods (DNase and RNase). RESULTS: Generally, the cells surrounding soft tissues were successfully removed, but none protocol removed cells from the tracheal cartilage. However, longer protocols were more effective. The cost-benefits relation of the enzymatic processes was not favorable. It was possible to find out that the cartilaginous tissue submitted to the irradiation with LED 630nm and 475 nm showed an increased number of gaps without cells, but several cells were observed to be still present. CONCLUSION: The light-emitting diode is a promising tool for decellularization of soft tissues.

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PURPOSE: To obtain a decellularized tracheal scaffold associating traditional approaches with the novel light-emitting diode (LED) proposal. METHODS: This study was performed with New Zealand adult rabbits weighing 3.0 - 4.0 kg. Different protocols (22) were used combining physical (agitation and LED irradiation), chemical (SDS and Triton X-100 detergents), and enzymatic methods (DNase and RNase). RESULTS: Generally, the cells surrounding soft tissues were successfully removed, but none protocol removed cells from the tracheal cartilage. However, longer protocols were more effective. The cost-benefits relation of the enzymatic processes was not favorable. It was possible to find out that the cartilaginous tissue submitted to the irradiation with LED 630nm and 475 nm showed an increased number of gaps without cells, but several cells were observed to be still present. CONCLUSION: The light-emitting diode is a promising tool for decellularization of soft tissues. .

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RESUMO

PURPOSE: To obtain a decellularized tracheal scaffold associating traditional approaches with the novel light-emitting diode (LED) proposal. METHODS: This study was performed with New Zealand adult rabbits weighing 3.0 - 4.0 kg. Different protocols (22) were used combining physical (agitation and LED irradiation), chemical (SDS and Triton X-100 detergents), and enzymatic methods (DNase and RNase). RESULTS: Generally, the cells surrounding soft tissues were successfully removed, but none protocol removed cells from the tracheal cartilage. However, longer protocols were more effective. The cost-benefits relation of the enzymatic processes was not favorable. It was possible to find out that the cartilaginous tissue submitted to the irradiation with LED 630nm and 475 nm showed an increased number of gaps without cells, but several cells were observed to be still present. CONCLUSION: The light-emitting diode is a promising tool for decellularization of soft tissues.(AU)

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O objetivo deste estudo foi analisar o resultado do tratamento cirúrgico de aspergiloma pulmonar. Para tanto, foram avaliados 14 pacientes adultos (7 homens e 7 mulheres) e tratados no Hospital Universitário da Faculdade de Medicina de Botucatu, em Botucatu (SP), entre 1981 e 2009. Dados foram coletados dos registros médicos dos pacientes. Dez pacientes (71 por cento) apresentaram aspergiloma pulmonar simples, e 4 (29 por cento) apresentaram aspergiloma pulmonar complexo. O sintoma mais frequente foi hemoptise, e a pneumopatia preexistente mais prevalente foi tuberculose. Dois pacientes (14 por cento) foram submetidos a mais de um procedimento cirúrgico. Não houve mortalidade operatória. Metade dos pacientes apresentou complicações pós-operatórias, sendo fuga aérea prolongada e empiema as mais frequentes.

The objective of this study was to analyze the outcome of surgical treatment of pulmonary aspergilloma. To that end, we evaluated 14 adult patients so treated between 1981 and 2009 at the Botucatu School of Medicine University Hospital, in the city of Botucatu, Brazil. Data were collected from the medical records of the patients. Ten patients (71 percent) presented with simple pulmonary aspergilloma, and 4 (29 percent) presented with complex pulmonary aspergilloma. Hemoptysis was the most common symptom, and tuberculosis was the most prevalent preexisting lung disease. Two patients (14 percent) underwent surgery on more than one occasion. There were no intraoperative deaths. Half of the patients developed postoperative complications, prolonged air leak and empyema being the most common.

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The objective of this study was to analyze the outcome of surgical treatment of pulmonary aspergilloma. To that end, we evaluated 14 adult patients so treated between 1981 and 2009 at the Botucatu School of Medicine University Hospital, in the city of Botucatu, Brazil. Data were collected from the medical records of the patients. Ten patients (71%) presented with simple pulmonary aspergilloma, and 4 (29%) presented with complex pulmonary aspergilloma. Hemoptysis was the most common symptom, and tuberculosis was the most prevalent preexisting lung disease. Two patients (14%) underwent surgery on more than one occasion. There were no intraoperative deaths. Half of the patients developed postoperative complications, prolonged air leak and empyema being the most common.

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OBJETIVO: Verificar a proporção de pacientes com baciloscopia negativa no pré-operatório e que apresentaram TB ativa na peça cirúrgica. MÉTODOS: Estudo retrospectivo de pacientes com diagnóstico histopatológico de TB ativa ou sequelar e operados entre os anos de 2003 e 2006 em um hospital universitário. Foram pesquisados antecedentes e aspectos clínicos relativos à doença, pesquisa de bacilos álcool-ácido resistentes (BAAR), tipo de cirurgia realizada e exame histopatológico da peça cirúrgica. RESULTADOS: Foram incluídos 43 pacientes, com média de idade de 44 ± 19 anos, sendo 27 do sexo masculino. Apresentavam história prévia de TB com tratamento adequado 28 pacientes, e 15 não referiam antecedentes para TB. O principal motivo da procura pelo serviço foi infecção de repetição, seguida por achados em exames de imagem. Dos 43 pacientes, foi pesquisado BAAR no pré-operatório em 35: 32 apresentaram resultados negativos e 3, resultados positivos. Dos 35 pacientes pesquisados, 26 apresentavam diagnóstico histopatológico de TB ativa e 9 de TB sequelar na peça cirúrgica; os outros 8 também foram diagnosticados com TB sequelar. A proporção de TB ativa em doentes com baciloscopia negativa foi de 72 por cento (23/32), e o de baciloscopia negativa em TB ativa foi de 88 por cento (23/26), sendo a pesquisa de BAAR positiva somente em 11,5 por cento (3/26). CONCLUSÕES: A baciloscopia direta tem rendimento muito baixo, e muitos pacientes mesmo já tratados podem permanecer com TB em atividade com baciloscopia negativa. A TB ativa pode ser confundida com infecções secundárias ou com câncer.

OBJECTIVE: To determine the proportion of negative preoperative sputum smear results among patients presenting active TB, as identified through the evaluation of surgical samples. METHODS: A retrospective study of patients undergoing surgery between 2003 and 2006 at a university hospital and receiving a histopathological diagnosis of active or latent TB. We reviewed patient histories, TB-related clinical aspects, acid-fast bacilli (AFB) test results, type of surgery performed and histopathological findings in surgical samples. RESULTS: We included 43 patients, 27 of whom were male. The mean age was 44 ± 19 years. Twenty-eight patients had a history of TB (treated appropriately), and 15 reported no history of the disease. The main reason for seeking treatment was recurrent infection, followed by alterations seen in imaging studies. Of the 43 patients, 35 underwent preoperative AFB testing: 32 tested negative, and 3 tested positive. Among those 35 patients, the histopathological diagnosis was active TB in 26 and latent TB in 9. The 8 patients not submitted to preoperative AFB testing were also diagnosed with latent TB. The proportion of active TB in patients with negative sputum smear results was 72 percent (23/32), whereas that of negative sputum smear results in patients with active TB was 88 percent (23/26). Only 11.5 percent (3/26) of the patients had tested positive for AFB. CONCLUSIONS: Direct sputum smear microscopy has a very low yield. Many previously treated patients can present negative sputum smear results and yet have active TB. Active TB can be mistaken for secondary infections or for cancer.

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OBJECTIVE: To analyze principal histological types of lung cancer, as well as the staging, treatment and survival of lung cancer patients. METHODS: This was a retrospective study based on the analysis of medical charts of patients treated at the Botucatu School of Medicine Hospital das Clínicas over a six-year period. RESULTS: From January of 2000 to January of 2006, 240 patients with lung cancer, most (64%) of whom were male, were treated. The most common histological type was squamous cell carcinoma (37.5%), followed by adenocarcinoma (30%), neuroendocrine carcinoma (19.6%) and large cell carcinoma (6.6%). Only 131 patients (54.6%) were treated. Of those, 52 patients (39.7%) received only chemotherapy, 32 (24.4%) were treated with chemotherapy combined with radiotherapy, and 47 (35.9%) were submitted to surgery alone or surgery accompanied by chemotherapy, with or without radiotherapy. Only 27 patients (20.6%) were submitted to surgery alone. Concerning staging, 34.4% presented stage IV at the time of diagnosis, 20.6% presented stage IIIB, 16.8% presented stage IIIA, and the remaining 28.2% were classified as stage I or II. Five-year survival was 65% for those in stage I and 25% for those in the remaining stages. CONCLUSIONS: Of the various histological types, the most common was squamous cell carcinoma and the least common was large cell carcinoma. Most cases presented advanced stages at the moment of diagnosis, and less than 30% of the cases presented early stages. This accounts for the low survival rate and the small number of patients submitted to surgical treatment alone, the majority being submitted to chemotherapy alone.

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OBJETIVO: Analisar os principais tipos histológicos, estádio, tratamento e sobrevida dos portadores de câncer de pulmão. MÉTODOS: Estudo retrospectivo a partir da análise dos prontuários de pacientes acompanhados no Hospital das Clínicas da Faculdade de Medicina de Botucatu, num período de seis anos. RESULTADOS: De janeiro de 2000 a janeiro de 2006, foram acompanhados 240 doentes com câncer de pulmão, com predominância do sexo masculino (64 por cento). O tipo histológico mais freqüente foi o carcinoma escamoso (37,5 por cento), seguido pelo adenocarcinoma (30 por cento), carcinoma neuroendócrino (19,6 por cento) e carcinoma de grandes células (6,6 por cento). Apenas 131 pacientes (54,6 por cento) foram tratados. Destes, 52 pacientes (39,7 por cento) foram submetidos à quimioterapia exclusiva, 32 (24,4 por cento) realizaram quimioterapia associada à radioterapia e 47 (35,9 por cento) foram submetidos à cirurgia associada ou não à quimioterapia exclusiva e/ou radioterapia. Somente 27 pacientes (20,6 por cento) foram submetidos à cirurgia exclusiva.Em relação ao estadiamento, 34,4 por cento apresentavam, no momento do diagnóstico, estádio IV, 20,6 por cento estádio IIIB, 16,8 por cento estádio IIIA e os outros 28,2 por cento pertenciam aos estádios I e II. A sobrevida em cinco anos foi de 65 por cento para o estádio I e 25 por cento para os estádios remanescentes. CONCLUSÕES: O tipo histológico predominante foi o carcinoma escamoso e o de menor freqüência foi o carcinoma de grandes células. A maioria se encontrava em estádio avançado ao diagnóstico, estando nos estádios iniciais menos de 30 por cento dos casos. Isto justifica a baixa sobrevida e a pequena quantidade de pacientes submetidos ao tratamento cirúrgico exclusivo, em comparação à maioria que foi submetida à quimioterapia exclusiva.

OBJECTIVE: To analyze principal histological types of lung cancer, as well as the staging, treatment and survival of lung cancer patients. METHODS: This was a retrospective study based on the analysis of medical charts of patients treated at the Botucatu School of Medicine Hospital das Clínicas over a six-year period. RESULTS: From January of 2000 to January of 2006, 240 patients with lung cancer, most (64 percent) of whom were male, were treated. The most common histological type was squamous cell carcinoma (37.5 percent), followed by adenocarcinoma (30 percent), neuroendocrine carcinoma (19.6 percent) and large cell carcinoma (6.6 percent). Only 131 patients (54.6 percent) were treated. Of those, 52 patients (39.7 percent) received only chemotherapy, 32 (24.4 percent) were treated with chemotherapy combined with radiotherapy, and 47 (35.9 percent) were submitted to surgery alone or surgery accompanied by chemotherapy, with or without radiotherapy. Only 27 patients (20.6 percent) were submitted to surgery alone. Concerning staging, 34.4 percent presented stage IV at the time of diagnosis, 20.6 percent presented stage IIIB, 16.8 percent presented stage IIIA, and the remaining 28.2 percent were classified as stage I or II. Five-year survival was 65 percent for those in stage I and 25 percent for those in the remaining stages. CONCLUSIONS: Of the various histological types, the most common was squamous cell carcinoma and the least common was large cell carcinoma. Most cases presented advanced stages at the moment of diagnosis, and less than 30 percent of the cases presented early stages. This accounts for the low survival rate and the small number of patients submitted to surgical treatment alone, the majority being submitted to chemotherapy alone.

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