The host-parasite interaction during early filarial nematode migration is poorly understood. The objective of this study was to develop a model of early cutaneous filarid migration using Brugia pahangi in the jird (gerbil) host and measure the histologic and cytokine responses during this period. Male gerbils were intradermally inoculated in the left hindlimb with 100 B. pahangi L3 then necropsied at 3 hours, 24 hours, 3 days, 7 days, and 28 days post-infection. Larvae were recovered and tissues collected for histology and cytokine measurement. At 3 hours, most larvae (96.3%) were recovered from tissues associated with the infection site. Migration away from the infection site occurred within 24 hours. By 7 days, larvae were dispersed throughout the lymphatic system, including the spermatic cord lymphatics. Larvae were identified on histologic exam at all time points and were located in the dermis, muscle, lymphatic vessels, and lymph nodes. Predominantly neutrophilic inflammation was frequently present around larvae in the dermis and muscle at 3 and 24 hours. Levels of the cytokines IL-6, TNF, IFN-gamma, and IL-4 were measured in the spleen and popliteal and renal lymph nodes. IL-6 and TNF both showed a peak at 3 hours followed by consistent decline in all tissues. No clear increase in expression was appreciated for IFN-gamma. IL-4 remained low through 7 days and rose by 28 days in all tissues. These results indicate the ability of filarid L3 to rapidly migrate through host tissue and they support intradermal gerbil infection as a model for early filariasis. Cytokine analysis and histology indicated an acute host inflammatory response following initial infection, with Th2 polarization occurring later in the course of infection.

Summer pasture-associated obstructive pulmonary disease (SPAOPD), a naturally occurring airway disease of horses, is characterized by clinical exacerbation associated with exposure to pasture environment during the summer. Aeroallergens are believed to trigger exacerbation of SPAOPD, cytokines are likely associated with the anamnestic response to aeroallergens, and endothelin (ET)-1 is a potential mediator of airway obstruction. The goal of this dissertation was to describe and explore the interaction of aeroallergens triggering inflammation and T lymphocytes cytokine profile with the recruitment and activation of neutrophils and synthesis of ET-1 by mononuclear leukocytes and airway epithelial cells. The temporal pattern of clinical exacerbation was associated with hot and humid conditions and with increases in grass pollen and mold spore counts. Circulating concentrations of ET-1 were increased during clinical exacerbation of SPAOPD compared with remission and controls. Gene expression of ET-1 and cytokines, interleukin (IL)-8 and IL-4, but not interferon (IFN)-γ, tended to be greater in lungs of SPAOPD-affected than non-affected horses. The immunoreactive ET-1 distribution tended to be greater in airway tissues of affected horses. The putative aeroallergens, grass pollen & mold spores, and ET-1 induced neutrophil activation and chemotaxis in vitro. Putative aeroallergens induced IL-4 and IFN-γ expression and up-regulation of ET-1 release in mononuclear leukocytes. Cultures of airway epithelial cells were established under air-liquid interface and microgravity conditions and evaluated for differentiation. Cytokines IL-4 and tumor necrosis factor (TNF)-α induced up-regulation and directional (basolateral) release of ET-1 by differentiated airway epithelial cells, grown under air-liquid interface.

No description available.

INTRODUÇÃO: Embora os avanços na oncologia sejam significativos, o câncer continua sendo um desafio para a ciência médica. Neste contexto, o diagnóstico precoce assume grande relevância, visto que as ferramentas diagnósticas têm permitido o planejamento terapêutico e a definição mais precisa do prognóstico. Dentre as ferramentas mais utilizadas na Medicina Veterinária destacam-se a histopatologia e a imuno-histoquímica. O presente trabalho, além de definir a casuística das neoplasias mamárias caninas, faz uma comparação entre os resultados histopatológicos e imunohistoquímicos permitindo a definição de assinaturas morfológicas e moleculares associadas a parâmetros de pior prognóstico já definidos pela literatura. MÉTODOS: Foram analisadas 129 amostras parafinadas de carcinoma mamário em cadelas por histopatologia e imuno-histoquímica, correlacionando o perfil de expressão das proteínas COX-2, HER-2, Ki-67 e E-caderina, vimentina e p63 com os subtipos histopatológicos de neoplasias mamárias em cadelas definidos na histopatologia. RESULTADOS: Das 129 amostras 7,7% (10/129) eram não neoplásicas, 7,7% (10/129) eram benignas e 84,5% (109/129) eram malignas. O tipo de tumor mais frequente foi o carcinoma em tumor misto 26,3% (34/129). Das 109 cadelas com tumor mamário maligno, 67 (61,4%) apresentaram tumores grau I, ou de histopatologia mais favorável. Quarenta e dois cães (38,6%) tiveram tumores de grau II e III ou de pior prognóstico histológico. Os tumores de grau III apresentaram maior grau de necrose, infiltração linfocitária, invasão linfática, desmoplasia e microcalcificação que os tumores de grau I e II. Os painéis de expressão proteica revelados pela IHC evidenciaram correlação entre grau histológico e expressão de Ki-67, HER-2, COX-2, p63, vimentina e ecaderina. Considerando os tipos histológicos mais agressivos, como carcinomas sólidos e anaplásicos e carcinosarcoma, observou-se que 66% de carcinomas sólidos, 80% de carcinomas anaplásticos e 66% de carcinosarcomas apresentaram alto índice de proliferação pelo Ki67. Outros marcadores confirmaram a associação desses subtipos histológicos com outras variáveis de IHC de pior prognóstico. CONCLUSÕES: Os resultados deste estudo mostraram uma correlação entre os parâmetros histopatológicos e os marcadores imuno-histoquímicos no tumor de grau I, II e III. No entanto, alguns tumores de grau I podem apresentar um indicador de painel imuno-histoquímico de mau prognóstico e ser subestimados se apenas foram avaliados por histopatologia. Por esta razão, a definição de linhas de tratamento e o prognóstico baseados apenas na análise histopatológica é limitado e deve ser complementado por imuno-histoquímica. Além disso, uma alta prevalência de tumores malignos mamários e a semelhança de tipos histológicos e perfis de coloração imuno-histoquímica qualificam a população canina como modelo promissor para estudos de câncer translacional / INTRODUCTION: Despite significant advances in oncology, cancer remains a challenge for medical science. Early diagnosis is important in this context because the diagnostic tools have enabled therapeutic planning and more precise definition of the prognosis. Histopathology and immunohistochemistry are among the tools most used within veterinary medicine. In addition to defining a sample of cases of canine mammary neoplasia, the present study compared histopathological and immunohistochemical results and thus made it possible to define morphological and molecular signatures that were associated with parameters for worse prognoses that had already been defined in the literature. METHODS: A total of 129 paraffin-embedded mammary carcinoma samples were analyzed histopathologically and immunohistochemically. The expression profiles of the proteins COX-2, HER-2, Ki-67, E-cadherin, vimentin and p63 were correlated with the histopathological subtypes of breast neoplasms in female dogs that were defined. RESULTS: Out of the 129 samples, 7.7% (10/129) were non-neoplastic, 7.7% (10/129) were benign and 84.5% (109/129) were malignant. The most frequent tumor type was mixed-tumor carcinoma, in 26.3% (34/129). Among the 109 female dogs with malignant mammary tumors, 67 (61.4%) presented grade I tumors, or more favorable histopathology. Forty-two (38.6%) had grade II and III tumors or worse histological prognosis. Grade III tumors had higher degrees of necrosis, lymphocytic infiltration, lymphatic invasion, desmoplasia and microcalcification than did grade I and II tumors. The protein expression panels revealed through immunohistochemical analysis showed correlations between histological grade and expression of Ki-67, HER-2, COX-2, p63, vimentin and ecadherin. Among the more aggressive histological types such as solid and anaplastic carcinomas and carcinosarcoma, it was observed that 66% of solid carcinomas, 80% of anaplastic carcinomas and 66% of carcinosarcomas presented high proliferation rates, shown by Ki67. Other markers confirmed the association of these histological subtypes with other immunohistochemical variables for worse prognosis. CONCLUSIONS: The results from this study showed correlations between the histopathological parameters and the immunohistochemical markers in tumors of grades I, II and III. However, it was seen that some grade I tumors with immunohistochemical panels indicating poor prognosis could be underestimated if they were only evaluated by histopathology. For this reason, definition of treatments and prognoses based only on histopathological analysis is limited and should be complemented by immunohistochemistry. In addition, the high prevalence of malignant mammary tumors and the similarity of histological types and immunohistochemical staining profiles qualify the canine population as a promising model for translational cancer studies

INTRODUÇÃO: Embora os avanços na oncologia sejam significativos, o câncer continua sendo um desafio para a ciência médica. Neste contexto, o diagnóstico precoce assume grande relevância, visto que as ferramentas diagnósticas têm permitido o planejamento terapêutico e a definição mais precisa do prognóstico. Dentre as ferramentas mais utilizadas na Medicina Veterinária destacam-se a histopatologia e a imuno-histoquímica. O presente trabalho, além de definir a casuística das neoplasias mamárias caninas, faz uma comparação entre os resultados histopatológicos e imunohistoquímicos permitindo a definição de assinaturas morfológicas e moleculares associadas a parâmetros de pior prognóstico já definidos pela literatura. MÉTODOS: Foram analisadas 129 amostras parafinadas de carcinoma mamário em cadelas por histopatologia e imuno-histoquímica, correlacionando o perfil de expressão das proteínas COX-2, HER-2, Ki-67 e E-caderina, vimentina e p63 com os subtipos histopatológicos de neoplasias mamárias em cadelas definidos na histopatologia. RESULTADOS: Das 129 amostras 7,7% (10/129) eram não neoplásicas, 7,7% (10/129) eram benignas e 84,5% (109/129) eram malignas. O tipo de tumor mais frequente foi o carcinoma em tumor misto 26,3% (34/129). Das 109 cadelas com tumor mamário maligno, 67 (61,4%) apresentaram tumores grau I, ou de histopatologia mais favorável. Quarenta e dois cães (38,6%) tiveram tumores de grau II e III ou de pior prognóstico histológico. Os tumores de grau III apresentaram maior grau de necrose, infiltração linfocitária, invasão linfática, desmoplasia e microcalcificação que os tumores de grau I e II. Os painéis de expressão proteica revelados pela IHC evidenciaram correlação entre grau histológico e expressão de Ki-67, HER-2, COX-2, p63, vimentina e ecaderina. Considerando os tipos histológicos mais agressivos, como carcinomas sólidos e anaplásicos e carcinosarcoma, observou-se que 66% de carcinomas sólidos, 80% de carcinomas anaplásticos e 66% de carcinosarcomas apresentaram alto índice de proliferação pelo Ki67. Outros marcadores confirmaram a associação desses subtipos histológicos com outras variáveis de IHC de pior prognóstico. CONCLUSÕES: Os resultados deste estudo mostraram uma correlação entre os parâmetros histopatológicos e os marcadores imuno-histoquímicos no tumor de grau I, II e III. No entanto, alguns tumores de grau I podem apresentar um indicador de painel imuno-histoquímico de mau prognóstico e ser subestimados se apenas foram avaliados por histopatologia. Por esta razão, a definição de linhas de tratamento e o prognóstico baseados apenas na análise histopatológica é limitado e deve ser complementado por imuno-histoquímica. Além disso, uma alta prevalência de tumores malignos mamários e a semelhança de tipos histológicos e perfis de coloração imuno-histoquímica qualificam a população canina como modelo promissor para estudos de câncer translacional / INTRODUCTION: Despite significant advances in oncology, cancer remains a challenge for medical science. Early diagnosis is important in this context because the diagnostic tools have enabled therapeutic planning and more precise definition of the prognosis. Histopathology and immunohistochemistry are among the tools most used within veterinary medicine. In addition to defining a sample of cases of canine mammary neoplasia, the present study compared histopathological and immunohistochemical results and thus made it possible to define morphological and molecular signatures that were associated with parameters for worse prognoses that had already been defined in the literature. METHODS: A total of 129 paraffin-embedded mammary carcinoma samples were analyzed histopathologically and immunohistochemically. The expression profiles of the proteins COX-2, HER-2, Ki-67, E-cadherin, vimentin and p63 were correlated with the histopathological subtypes of breast neoplasms in female dogs that were defined. RESULTS: Out of the 129 samples, 7.7% (10/129) were non-neoplastic, 7.7% (10/129) were benign and 84.5% (109/129) were malignant. The most frequent tumor type was mixed-tumor carcinoma, in 26.3% (34/129). Among the 109 female dogs with malignant mammary tumors, 67 (61.4%) presented grade I tumors, or more favorable histopathology. Forty-two (38.6%) had grade II and III tumors or worse histological prognosis. Grade III tumors had higher degrees of necrosis, lymphocytic infiltration, lymphatic invasion, desmoplasia and microcalcification than did grade I and II tumors. The protein expression panels revealed through immunohistochemical analysis showed correlations between histological grade and expression of Ki-67, HER-2, COX-2, p63, vimentin and ecadherin. Among the more aggressive histological types such as solid and anaplastic carcinomas and carcinosarcoma, it was observed that 66% of solid carcinomas, 80% of anaplastic carcinomas and 66% of carcinosarcomas presented high proliferation rates, shown by Ki67. Other markers confirmed the association of these histological subtypes with other immunohistochemical variables for worse prognosis. CONCLUSIONS: The results from this study showed correlations between the histopathological parameters and the immunohistochemical markers in tumors of grades I, II and III. However, it was seen that some grade I tumors with immunohistochemical panels indicating poor prognosis could be underestimated if they were only evaluated by histopathology. For this reason, definition of treatments and prognoses based only on histopathological analysis is limited and should be complemented by immunohistochemistry. In addition, the high prevalence of malignant mammary tumors and the similarity of histological types and immunohistochemical staining profiles qualify the canine population as a promising model for translational cancer studies