Effect of natural porcine surfactant in Staphylococcus aureus induced pro-inflammatory cytokines and reactive oxygen species generation in monocytes and neutrophils from human blood

Surfacen (R) is a clinical surfactant preparation of porcine origin. in the present study, we have evaluated the effect of Surfacen (R) in the modulation of oxidative burst in monocytes and neutrophils in human blood and proinflammatory cytokine production in peripheral blood mononuclear cells (PBMC). Reactive oxygen species (ROS) level was measured in monocytes and neutrophils by flow cytometry using 2,7-dichlorofluorescein diacetate (DCFH-DA) as substrate, while, tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 levels were estimated in PBMC supernatant by enzyme-linked immunosorbent assays (ELISA). Our results show that Staphylococcus aureus-induced ROS level was slightly affected by Surfacen (R) added to whole blood monocytes and neutrophils. the time course experiments of pre-incubation with Surfacen (R) showed no significant increase of ROS level at 2 h; however, the ROS level decreased when pre incubated for 4 h and 6 h with Surfacen (R). Pre-incubation of PBMC cells with Surfacen (R) at 0.125 and 0.5 mg/mL showed a dose-dependent suppression of TNF-alpha levels measured after 4 h of S. aureus stimulation, an effect less impressive when cells were stimulated for 24 h. A similar behavior was observed in IL-6 release. in summary, the present study provides experimental evidence supporting an anti-inflammatory role of Surfacen (R) in human monocytes and neutrophils in vitro. (C) 2014 Elsevier B.V. All rights reserved.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Ctr Nacl Sanidad Agr CENSA, San Jose de Las Lajas, Mayabeque, CubaUniversidade Federal de São Paulo, Escola Paulista Med, Hosp São Paulo, Div Infect Dis, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Hosp São Paulo, Div Infect Dis, São Paulo, BrazilCAPES: AUX-PE-MESCUBA: 103/10Web of Scienc

IFN-α induces a preferential long-lasting expression of MHC class I in human pancreatic beta cells

Aims/hypothesis IFN-α, a cytokine expressed in human islets from individuals affected by type 1 diabetes, plays a key role in the pathogenesis of diabetes by upregulating inflammation, endoplasmic reticulum (ER) stress and MHC class I overexpression, three hallmarks of islet histology in early type 1 diabetes. We tested whether expression of these mediators of beta cell loss is reversible upon IFN-α withdrawal or IFN-α pathway inhibition. Methods IFN-α-induced MHC class I overexpression, ER stress and inflammation were evaluated by flow cytometry, immunofluorescence and real-time PCR in human EndoC-βH1 cells or human islets exposed to IFN-α with or without the presence of Janus kinase (JAK) inhibitors. Protein expression was evaluated by western blot. Results IFN-α-induced expression of inflammatory and ER stress markers returned to baseline after 24–48 h following cytokine removal. In contrast, MHC class I overexpression at the cell surface persisted for at least 7 days. Treatment with JAK inhibitors, when added with IFN-α, prevented MHC class I overexpression, but when added 24 h after IFN-α exposure these inhibitors failed to accelerate MHC class I return to baseline. Conclusions/interpretation IFN-α mediates a long-lasting and preferential MHC class I overexpression in human beta cells, which is not affected by the subsequent addition of JAK inhibitors. These observations suggest that IFN-α-stimulated long-lasting MHC class I expression may amplify beta cell antigen presentation during the early phase of type 1 diabetes and that IFN-α inhibitors might need to be used at very early stages of the disease to be effective

Ácido 3,4,5-Trimetoxicinâmico e seu Potencial Terapêutico: Uma Revisão / 3,4,5-Trimethoxycinnamic Acid and Its Therapeutic Potential: A Review

As plantas medicinais tem se constituído como uma das principais fontes na obtenção de novos fármacos e no desenvolvimento de medicamentos. A fitoterapia é praticada na Medicina Tradicional Chinesa há séculos e plantas como a Polygala tenuifolia Wild são amplamente usadas no tratamento da insônia, ansiedade, inquietação e desorientação. Um dos principais metabólitos ativos presentes em raízes desta planta é o ácido 3,4,5 trimetoxicinâmico (TMCA). Portanto, o objetivo do presente estudo foi buscar na literatura científica os principais métodos desenvolvidos para identificação e quantificação do TMCA em misturas, o perfil farmacocinético, a biodisponibilidade e as atividades farmacológicas do TMCA. Uma revisão sistemática foi realizada, na qual buscou-se artigos científicos indexados no ScienceDirect, Web of Science, SciELO, LILACS e PubMed, utilizando os seguintes descritores: 3,4,5-trimethoxycinnamic acid; TMCA e activity. Foram selecionados 11 artigos que descreviam as metodologias viáveis para identificação e quantificação do TMCA em amostras biológicas, o seu perfil farmacocinético e a sua biodisponibilidade quando administrados pela via oral em ratos, bem como suas atividades farmacológicas, tais como sedativo, ansiolítico, antidepressivo, anti-estressor e modulador do sistema GABAérgico. Em conclusão, os dados indicam que o TMCA é um composto que apresenta importantes atividades farmacológicas. Contudo, são poucos os estudos não clínicos e não há registro de estudos clínicos sobre os possíveis efeitos terapêuticos do TMCA

Imbalance of naive and memory T lymphocytes with sustained high cellular activation during the first year of life from uninfected children born to HIV-1-infected mothers on HAART

The immune consequences of in utero HIV exposure to uninfected children whose mothers were submitted to highly active antiretroviral therapy (HAART) during gestation are not well defined. We evaluated 45 HIV-exposed uninfected (ENI) neonates and 45 healthy unexposed control (CT) neonates. All HIV-infected mothers received HAART during pregnancy, and the viral load at delivery was <50 copies/mL for 56.8%. Twenty-three ENI neonates were further evaluated after 12 months and compared to 23 unexposed healthy age-matched infants. Immunophenotyping was performed by flow cytometry in cord and peripheral blood. Cord blood lymphocyte numbers did not differ between groups. However, ENI neonates had a lower percentage of naive T cells than CT neonates (CD4+, 76.6 vs 83.1%, P < 0.001; CD8+, 70.9 vs 79.6%, P = 0.003) and higher percentages of central memory T cells than CT neonates (CD4+, 13.9 vs 8.7%, P < 0.001; CD8+, 8.6 vs 4.8%, P = 0.001). CD38 mean fluorescence intensity of T cells was higher in ENI neonates (CD4+, 62.2 vs 52.1, P = 0.007; CD8+, 47.7 vs 35.3, P < 0.001). At 12 months, ENI infants still had higher mean fluorescence intensity of CD38 on T cells (CD4+, 34.2 vs 23.3, P < 0.001; CD8+, 26.8 vs 19.4, P = 0.035). Despite effective maternal virologic control at delivery, HIV-exposed uninfected children were born with lower levels of naive T cells. Immune activation was present at birth and remained until at least 12 months of age, suggesting that in utero exposure to HIV causes subtle immune abnormalities.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo (UNIFESP) Disciplina de Infectologia PediátricaUniversidade Federal de São Paulo (UNIFESP) Departamento de Pediatria Disciplina de Pediatria NeonatalUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de MedicinaUniversidade de São Paulo Instituto de Medicina Tropical de São Paulo Laboratório de VirologiaUNIFESP, Disciplina de Infectologia PediátricaUNIFESP, Depto. de Pediatria Disciplina de Pediatria NeonatalUNIFESP, EPM, Depto. de MedicinaFAPESP: 01/11011-6SciEL

A EFICÁCIA DO ESTABELECIMENTO DE PADRÕES DE QUALIDADE AMBIENTAL

The National Environment Policy, Law 6938/81, has the function of providing a coherent conceptual and operational guide for the country’s environmental laws. In order for achieving this purpose, objectives, instruments and a central organizational system for the environmental management were established. Among the instruments it was provided the establishment of environmental quality standards. After more than thirty years of this prediction, there are not concrete studies to evaluate the results obtained so far. Given the need for such studies, this article examined the effectiveness of the establishment of environmental quality standards, that is, if it has produced the expected goals. The research was exploratory, outlined by bibliographic and documentary methods. The results showed that the legal provision was fulfi lled, with current quality standards for water, air, noise sound and soil, established by predefined classes of use of the territory. However, these patterns have not been allocated as quality targets, able to ensure the required environmental conditions in the country. The prevailing action is the use of command and control measures to reduce pollution, especially the application of emission limits for specific sources, without the expected observation of the limits specifi ed by the standards of environmental quality. In addition, the lack of planning of the use of the territory and the shortcomings in monitoring environmental quality in Brazil harm the appropriation of established standards. Thus, it is concluded that the environmental quality standards have not been effective because the proposed objectives were not achieved.  A Política Nacional do Meio Ambiente, Lei nº6938/81, tem a função de fornecer uma coerência conceitual e operacional para as leis ambientais do país. Para atingir esse propósito, princípios, objetivos, instrumentos e um sistema organizacional para a gestão ambiental foram estabelecidos. Dentre os instrumentos, foi previsto o estabelecimento de padrões de qualidade ambiental. Passados mais de trinta anos dessa previsão, não há estudos concretos que avaliem os resultados obtidos por este instrumento. Dada a necessidade desses estudos, este artigo analisou a eficácia do estabelecimento de padrões de qualidade ambiental, isto é, verificou-se o instrumento produziu os objetivos esperados. A pesquisa foi exploratória, delineada por métodos de pesquisa bibliográfica e documental. Os resultados demonstraram que a previsão legal foi cumprida, estando vigentes padrões de qualidade para água, ar, ruídos sonoros e solo, estabelecidos por classes predefinidas de uso do território. No entanto, esses padrões não foram apropriados como metas de qualidade, capazes de assegurar as condições ambientais requeridas no país. Prevalece a utilização de medidas de comando e controle para a redução da poluição, sobretudo a aplicação de limites de emissão para fontes específicas, sem a esperada observação dos limites indicados pelos padrões de qualidade ambiental. Além disso, a falta de planejamento do uso do território e as deficiências no monitoramento da qualidade ambiental no Brasil prejudicam a apropriação dos padrões instituídos. Assim, conclui-se que os padrões de qualidade ambiental não têm sido eficazes, pois os objetivos propostos não foram alcançados

Effect of refrigeration on post-harvest flowers

Cut flowers have a very limited life after they have been cut off from the mother plant, as survival on their own reserves is generally low due to the special morphological and physiological characteristics of their tissues. The use of refrigeration for storage of flower cuttings is very important because it reduces water loss, senescence, infections caused by bacteria and fungi, thus extending the shelf-life of flowers during the storage period. Therefore, the aim of the present work is to show differences between requirements of various species of flowers during refrigerated storage.Keywords: Cooling, post-harvest, conservation, flowers, cold injur