Present understanding of mediators and experimental models of sepsis

The author presents a reviewed description about the inflammatory response during sepsis, viewing the mainly mediators in this process, as cytokines and nitric oxide, and the role of these mediators in the evolution of this disease. This aspect is not so linear and simple, because the importance of each mediators depend on experimental model, animal species and sepsis stage. Furthermore, it will be reviewed the principal experimental models used for the study of sepsis, discussing the advantage of each one and their contribution for the comprehension of the disease. It has no doubt about the importance of all experimental model of sepsis and septic shock, however it is crucial to distinguish the good and bad features about each model, in order to concern successful results for clinic trials.A autora apresenta uma revisão sobre a resposta inflamatória durante a sepse, abordando os principais mediadores envolvidos no processo, tais como citocinas e óxido nítrico, bem como o papel desses mediadores na evolução da doença. Esse aspecto abordado não é tão simples e pontual, pois a relevância desses mediadores inflamatórios, na sepse, varia de acordo com muitos fatores, entre eles, com o modelo experimental utilizado, a espécie animal e o estágio da doença. Ainda, serão revisados os modelos experimentais mais utilizados para o estudo da sepse, discutindo-se as vantagens de cada modelo e a sua contribuição para a compreensão da doença. Não há dúvida que os modelos experimentais, utilizados hoje em dia, contribuem bastante para o entendimento de sepse e choque séptico. Entretanto, é importante saber discernir os pontos fortes e fracos do modelo, possibilitando uma real extensão dos resultados experimentais para testes clínicos

Reduction mastoplasty with submuscular implants for breast symmetrization in patients undergoing mastectomy

INTRODUCTION: Breast reconstruction with expanders/implants is one of the most common techniques used for the treatment of mastectomy-induced sequelae, due to the reduced surgical time and morbidity. However, the maintenance of long-term symmetrization in the contralateral breast remains a major challenge. The procedure of reduction mastoplasty has been developed, and is performed by positioning a submuscular implant in the contralateral breast of patients undergoing breast reconstruction. METHODS: A total of 31 patients were included in the study. Their primary characteristics were glandular resection, combined with implant insertion in the subpectoral plane. Complications, shape, symmetry, and volume were subsequently evaluated. RESULTS: A low incidence of complications and surgical revisions was observed, with no cases of implant loss. Good breast symmetry was achieved. CONCLUSION: Reduction mastoplasty with submuscular implants proved to be a safe procedure, and resulted in good breast symmetry in patients who underwent mastectomy

Controversial themes in liposuction: national opinion survey of members of the Brazilian Society of Plastic Surgery (Update Liposuction Survey)

INTRODUCTION: Liposuction is the second most commonly performed surgical procedure worldwide. However, many liposuction procedures are controversial. In this context, expert opinion surveys may help elucidate topics lacking consensus. The objective of this survey was to interview plastic surgeons who are members of the Brazilian Society of Plastic Surgery (Sociedade Brasileira de Cirurgia Plástica [SBCP]), the Update Liposuction Survey (ULS/SBCP), to assess their opinions about controversial topics in liposuction. METHODS: A link to a questionnaire containing 11 questions involving liposuction (ULS/SBCP) was sent electronically to all SBCP members. The email was sent in three instances and with the provision of incentives to promote a higher response rate. RESULTS: Of the 4,957 contacted plastic surgeons, 917 responded (response rate, 18.5%). The results are being analyzed for publication in full

Pleiotropic antifibrotic actions of aspirin-triggered resolvin D1 in the lungs

Introduction: Pulmonary fibrosis is a destructive, progressive disease that dramatically reduces life quality of patients, ultimately leading to death. Therapeutic regimens for pulmonary fibrosis have shown limited benefits, hence justifying the efforts to evaluate the outcome of alternative treatments. Methods: Using a mouse model of bleomycin (BLM)-induced lung fibrosis, in the current work we asked whether treatment with pro-resolution molecules, such as pro-resolving lipid mediators (SPMs) could ameliorate pulmonary fibrosis. To this end, we injected aspirin-triggered resolvin D1 (7S,8R,17R-trihydroxy-4Z,9E,11E,13Z,15E19Z-docosahexaenoic acid; ATRvD1; i.v.) 7 and 10 days after BLM (intratracheal) challenge and samples were two weeks later. Results and discussion: Assessment of outcome in the lung tissues revealed that ATRvD1 partially restored lung architecture, reduced leukocyte infiltration, and inhibited formation of interstitial edema. In addition, lung tissues from BLM-induced mice treated with ATRvD1 displayed reduced levels of TNF-α, MCP-1, IL-1-β, and TGF-β. Of further interest, ATRvD1 decreased lung tissue expression of MMP-9, without affecting TIMP-1. Highlighting the beneficial effects of ATRvD1, we found reduced deposition of collagen and fibronectin in the lung tissues. Congruent with the anti-fibrotic effects that ATRvD1 exerted in lung tissues, α-SMA expression was decreased, suggesting that myofibroblast differentiation was inhibited by ATRvD1. Turning to culture systems, we next showed that ATRvD1 impaired TGF-β-induced fibroblast differentiation into myofibroblast. After showing that ATRvD1 hampered extracellular vesicles (EVs) release in the supernatants from TGF-β-stimulated cultures of mouse macrophages, we verified that ATRvD1 also inhibited the release of EVs in the bronco-alveolar lavage (BAL) fluid of BLM-induced mice. Motivated by studies showing that BLM-induced lung fibrosis is linked to angiogenesis, we asked whether ATRvD1 could blunt BLM-induced angiogenesis in the hamster cheek pouch model (HCP). Indeed, our intravital microscopy studies confirmed that ATRvD1 abrogates BLM-induced angiogenesis. Collectively, our findings suggest that treatment of pulmonary fibrosis patients with ATRvD1 deserves to be explored as a therapeutic option in the clinical setting.Fil: Guilherme, Rafael F.. Universidade Federal do Rio de Janeiro; BrasilFil: Silva, José Bruno N.F.. Universidade Federal do Rio de Janeiro; Brasil. Universidade Federal do Tocantins; BrasilFil: Waclawiack, Ingrid. Universidade Federal do Rio de Janeiro; BrasilFil: Fraga Junior, Vanderlei S.. Universidade Federal do Rio de Janeiro; BrasilFil: Nogueira, Thaís O.. Universidade Federal do Rio de Janeiro; BrasilFil: Pecli, Cyntia. Universidade Federal do Rio de Janeiro; BrasilFil: Araújo Silva, Carlla A.. Universidade Federal do Rio de Janeiro; BrasilFil: Magalhães, Nathalia S.. Ministerio de Salud de Brasil. Fundación Oswaldo Cruz. Instituto Oswaldo Cruz;Fil: Lemos, Felipe S.. Ministerio de Salud de Brasil. Fundación Oswaldo Cruz. Instituto Oswaldo Cruz;Fil: Bulant, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil; ArgentinaFil: Blanco, Pablo Javier. Laboratório Nacional para Computação Científica; BrasilFil: Serra, Rafaela. Universidade Federal do Rio de Janeiro; BrasilFil: Svensjö, Erik. Universidade Federal do Rio de Janeiro; BrasilFil: Scharfstein, Júlio. Universidade Federal do Rio de Janeiro; BrasilFil: Moraes, João A.. Universidade Federal do Rio de Janeiro; BrasilFil: Canetti, Claudio. Universidade Federal do Rio de Janeiro; BrasilFil: Benjamim, Claudia F.. Universidade Federal do Rio de Janeiro; Brasi

Alimentação popular em São Paulo (1920 a 1950): políticas públicas, discursos técnicos e práticas profissionais

This article discusses how the concept of lower-class eating habits came about and developed in the intellectual circles of São Paulo during the first half of the 20th century. It starts by reconstructing the elements of the debate around the income and ignorance of the underprivileged as the main reasons behind their bad eating habits. Then, it looks at the focal points for interventions and public policies proposed by the government to deal with the problem thus identified, namely: training methods to produce sanitation counselors capable of offering dietary guidance as well; popular educational campaigns and new learning sites in addition to schools (e.g. healthcare centers and households); lunch and other means of offering food at schools; and diagnostic studies about food intake and eating habits among laborers. Because they were translated into technical and scientific language, the proposals and policies implemented in São Paulo left traces in a variety of supporting documents and media (photographs, primers, posters, inquiry notebooks, and academic literature).O artigo discute a construção da idéia de alimentação popular nos meios intelectuais em São Paulo, na primeira metade do século XX. Para isso, reconstitui, como motivos da má alimentação, elementos do debate em torno da renda e da ignorância dos mais pobres. Identificado o problema, as propostas de intervenção e as políticas públicas concentraram-se em alguns setores, abordados neste trabalho: métodos para a formação de educadores sanitários aptos a atuar também na educação alimentar; campanhas de instrução popular e criação de novos lugares de aprendizado (além das escolas, os centros de saúde e os lares); merenda escolar e outras alternativas de alimentação nas escolas; e diagnósticos referentes ao conteúdo e à forma da alimentação dos operários. Traduzidas em discurso técnico-científicos, as propostas e políticas implementadas na cidade deixaram indícios em documentação de suporte e tipologia variados (fotografias, cartilhas, cartazes, cadernetas de inquéritos e textos acadêmicos).Universidade Federal de São Paulo (UNIFESP)UNIFESPSciEL

Evaluation of 3-(3-chloro-phenyl)-5-(4-pyridyl)-4,5-dihydroisoxazole as a Novel Anti-Inflammatory Drug Candidate

BACKGROUND: 3-(3-chloro-phenyl)-5-(4-pyridyl)-4,5-dihydroisoxazole (DIC) is a five-membered heterocyclic compound containing a N-O bond. The anti-inflammatory effects of this compound were studied both in vitro and in vivo. PRINCIPAL FINDINGS: DIC effectively decreased TNF-α and IL-6 release from LPS-stimulated macrophages in a dose dependent manner. DIC diminished the levels of COX-2 with subsequent inhibition of PGE(2) production. DIC also compromised HMGB1 translocation from the nucleus to the cytoplasm. Moreover, DIC prevented the nuclear translocation of NF-κB and inhibited the MAPK pathway. In vivo, DIC inhibited migration of neutrophils to the peritoneal cavity of mice. CONCLUSIONS: This study presents the potential utilization of a synthetic compound, as a lead for the development of novel anti-inflammatory drugs

Purinergic P2Y12 Receptor Activation in Eosinophils and the Schistosomal Host Response

Identifying new target molecules through which eosinophils secrete their stored proteins may reveal new therapeutic approaches for the control of eosinophilic disorders such as host immune responses to parasites. We have recently reported the expression of the purinergic P2Y12 receptor (P2Y12R) in human eosinophils; however, its functional role in this cell type and its involvement in eosinophilic inflammation remain unknown. Here, we investigated functional roles of P2Y12R in isolated human eosinophils and in a murine model of eosinophilic inflammation induced by Schistosoma mansoni (S. mansoni) infection. We found that adenosine 5’-diphosphate (ADP) induced human eosinophils to secrete eosinophil peroxidase (EPO) in a P2Y12R dependent manner. However, ADP did not interfere with human eosinophil apoptosis or chemotaxis in vitro. In vivo, C57Bl/6 mice were infected with cercariae of the Belo Horizonte strain of S. mansoni. Analyses performed 55 days post infection revealed that P2Y12R blockade reduced the granulomatous hepatic area and the eosinophilic infiltrate, collagen deposition and IL-13/IL-4 production in the liver without affecting the parasite oviposition. As found for humans, murine eosinophils also express the P2Y12R. P2Y12R inhibition increased blood eosinophilia, whereas it decreased the bone marrow eosinophil count. Our results suggest that P2Y12R has an important role in eosinophil EPO secretion and in establishing the inflammatory response in the course of a S. mansoni infection