Redistribution of the glycocalyx exposes phagocytic determinants on apoptotic cells.

Phagocytes remove dead and dying cells by engaging "eat-me" ligands such as phosphatidylserine (PtdSer) on the surface of apoptotic targets. However, PtdSer is obscured by the bulky exofacial glycocalyx, which also exposes ligands that activate "don't-eat-me" receptors such as Siglecs. Clearly, unshielding the juxtamembrane "eat-me" ligands is required for the successful engulfment of apoptotic cells, but the mechanisms underlying this process have not been described. Using human and murine cells, we find that apoptosis-induced retraction and weakening of the cytoskeleton that anchors transmembrane proteins cause an inhomogeneous redistribution of the glycocalyx: actin-depleted blebs emerge, lacking the glycocalyx, while the rest of the apoptotic cell body retains sufficient actin to tether the glycocalyx in place. Thus, apoptotic blebs can be engaged by phagocytes and are targeted for engulfment. Therefore, in cells with an elaborate glycocalyx, such as mucinous cancer cells, this "don't-come-close-to-me" barrier must be removed to enable clearance by phagocytosis.

Lysophosphatidylcholine Induces NLRP3 Inflammasome-Mediated Foam Cell Formation and Pyroptosis in Human Monocytes and Endothelial Cells.

Foam cells are specialized lipid-loaded macrophages derived from monocytes and are a key pathological feature of atherosclerotic lesions. Lysophosphatidylcholine (LPC) is a major lipid component of the plasma membrane with a broad spectrum of proinflammatory activities and plays a key role in atherosclerosis. However, the role of LPC in lipid droplet (LD) biogenesis and the modulation of inflammasome activation is still poorly understood. In the present study, we investigated whether LPC can induce foam cell formation through an analysis of LD biogenesis and determined whether the cell signaling involved in this process is mediated by the inflammasome activation pathway in human endothelial cells and monocytes. Our results showed that LPC induced foam cell formation in both types of cells by increasing LD biogenesis via a NLRP3 inflammasome-dependent pathway. Furthermore, LPC induced pyroptosis in both cells and the activation of the inflammasome with IL-1ß secretion, which was dependent on potassium efflux and lysosomal damage in human monocytes. The present study described the IL-1ß secretion and foam cell formation triggered by LPC via an inflammasome-mediated pathway in human monocytes and endothelial cells. Our results will help improve our understanding of the relationships among LPC, LD biogenesis, and NLRP3 inflammasome activation in the pathogenesis of atherosclerosis.

Análise dos fatores de risco na formação de seroma em abdominoplastia clássica / Analysis of risk factors for the formation of seroma in classical abdominoplasty

Introdução: A abdominoplastia é uma das cirurgias estéticas mais realizadas no Brasil. As complicações deste procedimento são diversas, sendo o seroma uma das mais frequentes. O objetivo do trabalho é identificar fatores de risco para formação de seroma tais como: índice de massa corporal (IMC), comorbidades, idade, hábitos e tempo de permanência de dreno. Métodos: Trata-se de um estudo retrospectivo com revisão de 94 prontuários de pacientes submetidos à abdominoplastia clássica no Serviço de Cirurgia Plástica e Queimados da Santa Casa de Misericórdia de São José do Rio Preto-SP, entre novembro de 2010 e novembro de 2013. Os fatores de risco para formação do seroma foram analisados utilizando-se o teste exato de Fisher ou Qui-quadrado. Considerou-se como resultado estatisticamente significativo o valor de p < 0,05. Resultados: O seroma foi identificado em 16 pacientes (17,02%) do total da amostra (n = 94). Não se observou significância estatística ao relacionar a elevação na incidência de seroma com o aumento do IMC, assim como os demais fatores de risco analisados. Houve relevância clínica quanto ao tempo de permanência do dreno. Pacientes que mantiveram o dreno por um período maior que um dia tiveram incidência menor de seroma. Conclusão: A formação do seroma deve ser considerada uma causa multifatorial. Os fatores de risco analisados não demonstraram estatisticamente aumento na incidência de seroma. Todavia, a permanência do dreno de sucção por um período maior que um dia demonstrou ser eficaz na prevenção do seroma.

Introduction: Abdominoplasty is one of the most common cosmetic surgeries in Brazil. The complications of this procedure are diverse, with seroma being one of the most frequent. The objective of this study was to identify the risk factors for the formation of seroma, such as increased body mass index, comorbidities, age, habits, and time of drain permanence. Methods: This was a retrospective study in which the medical records of 94 patients who underwent abdominoplasty at the Plastic Surgery and Burns Service of Santa Casa de Misericórdia de São José do Rio Preto-SP between November 2010 and November 2013 were reviewed. The risk factors for the formation of seroma were analyzed using Fisher's exact test and the Chi-square test, with the significance level set at p < 0.05. Results: Seroma was identified in 16 (17.02%) of the total patients (n = 94). No statistical significance was observed between increased incidence of seroma and increased BMI and other risk factors analyzed. Nevertheless, the time of drain permanence showed a clinical relevance. The patients who were maintained on the drain for > 1 day had a lower incidence of seroma. Conclusion: The causes of seroma should be considered multifactorial. The risk factors analyzed were not significantly related to the increased incidence of seroma. However, drain permanence for >1 day was effective in the prevention of seroma.

Schistosomal Lipids Activate Human Eosinophils via Toll-Like Receptor 2 and PGD2 Receptors: 15-LO Role in Cytokine Secretion.

Parasite-derived lipids may play important roles in host-pathogen interactions and immune evasion mechanisms. Remarkable accumulation of eosinophils is a characteristic feature of inflammation associated with parasitic disease, especially caused by helminthes. Infiltrating eosinophils are implicated in the pathogenesis of helminth infection by virtue of their capacity to release an array of tissue-damaging and immunoregulatory mediators. However, the mechanisms involved in the activation of human eosinophils by parasite-derived molecules are not clear. Here we investigated the effects and mechanisms of schistosomal lipids-induced activation of human eosinophils. Our results showed that stimulation of human eosinophils in vitro with total lipid extracts from adult worms of S. mansoni induced direct activation of human eosinophils, eliciting lipid droplet biogenesis, synthesis of leukotriene (LT) C4 and eoxin (EX) C4 (14,15 LTC4) and secretion of eosinophil pre-formed TGFß. We demonstrated that main eosinophil activating components within S. mansoni lipid extract are schistosomal-derived lysophosphatidylcholine (LPC) and prostaglandin (PG)D2. Moreover, TLR2 is up-regulated in human eosinophils upon stimulation with schistosomal lipids and pre-treatment with anti-TLR2 inhibited both schistosomal lipids- and LPC-, but not PGD2-, induced lipid droplet biogenesis and EXC4 synthesis within eosinophils, indicating that TLR2 mediates LPC-driven human eosinophil activation. By employing PGD2 receptor antagonists, we demonstrated that DP1 receptors are also involved in various parameters of human eosinophil activation induced by schistosomal lipids, but not by schistosomal LPC. In addition, schistosomal lipids and their active components PGD2 and LPC, triggered 15-LO dependent production of EXC4 and secretion of TGFß. Taken together, our results showed that schistosomal lipids contain at least two components-LPC and PGD2-that are capable of direct activation of human eosinophils acting on distinct eosinophil-expressed receptors, noticeably TLR2 as well as DP1, trigger human eosinophil activation characterized by production/secretion of pro-inflammatory and immunoregulatory mediators.

Schistosomal-derived lysophosphatidylcholine triggers M2 polarization of macrophages through PPARγ dependent mechanisms.

Mansonic schistosomiasis is a disease caused by the trematode Schistosoma mansoni, endemic to tropical countries. S. mansoni infection induces the formation of granulomas and potent polarization of Th2-type immune response. There is great interest in understanding the mechanisms used by this parasite that causes a modulation of the immune system. Recent studies from our group demonstrated that lipids of S. mansoni, including lysophosphatidylcholine (LPC) have immunomodulatory activity. In the present study, our aim was to investigate the role of lipids derived from S. mansoni in the activation and polarization of macrophages and to characterize the mechanisms involved in this process. Peritoneal macrophages obtained from wild type C57BL/6mice or bone marrow derived macrophages were stimulated in vitro with lipids extracted from adult worms of S. mansoni. We demonstrated that total schistosomal-derived lipids as well as purified LPC induced alternatively activated macrophages/M2 profile observed by increased expression of arginase-1, mannose receptor, Chi3l3, TGFß and production of IL-10 and PGE2 24h after stimulation. The involvement of the nuclear receptor PPARγ in macrophage response against LPC was investigated. Through Western blot and immunofluorescence confocal microscopy we demonstrated that schistosomal-derived LPC induces increased expression of PPARγ in macrophages. The LPC-induced increased expression of arginase-1 were significantly inhibited by the PPAR-γ antagonist GW9662. Together, these results demonstrate an immunomodulatory role of schistosomal-derived LPC in activating macrophages to a profile of the type M2 through PPARγ-dependent mechanisms, indicating a novel pathway for macrophage polarization triggered by parasite-derived LPC with potential implications to disease pathogenesis.

Epidemiologia dos traumas de face do serviço de cirurgia plástica e queimados da Santa Casa de Misericórdia de São José do Rio Preto / Epidemiology of facial trauma at the plastic surgery and burns service of the Santa Casa de Misericórdia de São José do Rio Preto

Introdução: O trauma é um dos principais problemas de saúde pública em todos os países, sendo os que acometem a região facial muito frequentes. O presente trabalho objetiva avaliar dados epidemiológicos de pacientes que sofreram trauma de face com fratura. Métodos: Estudo epidemiológico realizado por meio dos prontuários de 92 pacientes. Foram selecionados indivíduos com trauma facial de qualquer intensidade, no período de janeiro de 2009 a janeiro de 2013, e agrupados de acordo com a etiologia e a localização das fraturas. Os dados coletados foram apresentados em valores absolutos e porcentagens. Resultados: Houve prevalência de pacientes do sexo masculino. A etiologia do trauma de face mais encontrada foi a violência interpessoal, observada na maioria dos grupos, exceto naquele acima de 45 anos, cuja predominância etiológica foi de queda e acidente de automóvel. A incidência das causas variou de acordo com a faixa etária: < 18 anos, de 19 a 25 anos, de 26 a 35 anos, de 36 a 45 anos e > 45 anos. Setenta e cinco por cento das fraturas de mandíbula foram unilaterais e 25%, bilaterais. O tratamento cirúrgico de fixação com placas foi o mais utilizado. No nosso estudo, catorze pacientes apresentaram complicação pós-cirúrgica. Conclusão: Há necessidade de um atendimento sistematizado para os traumas faciais. A variação na faixa etária encontrada entre os pacientes estudados demonstra que o trauma facial abrange indivíduos em qualquer idade, embora seja maior entre os jovens. Acreditamos que o presente estudo epidemiológico possibilitará a melhora da qualidade no atendimento aos pacientes com trauma facial.

Introduction: Trauma is a major public health problem in all countries, and injuries involving the facial region are very common. This study aims to assess the epidemiological data of patients who suffered facial trauma with fracture. Methods: Epidemiological study conducted on 92 patient records. Individuals with facial trauma of any intensity presenting between January 2009 and January 2013 were selected and grouped according to the etiology and location of fractures. Data were presented as absolute values and percentages. Results: There was a higher prevalence of male patients. The most frequent cause of facial trauma was interpersonal violence in most groups, except for those over 45 years old, for whom the predominant causes were falls and car accidents. The frequency of the causes varied according to age: <18 years, 19-25 years old, 26-35 years old, 36-45 years and> 45 years. Seventy-five percent of mandibular fractures were unilateral and 25% bilateral. Surgical fixation with plates was the most common treatment. In our study, fourteen patients had postoperative complications. Conclusion: There is a need for systemized care for facial trauma. The variation in the age range found among the studied patients demonstrates that facial trauma includes individuals of any age, although it is more common among young people. We believe that this epidemiological study will enable the improvement of the quality of care for patients with facial trauma.

Perfil e avaliação dos resultados de pacientes submetidas à mamoplastia redutora / Patient profile and results evaluation after breast reduction

INTRODUÇÃO: A hipertrofia mamária é relatada como fonte de sofrimento físico e emocional em mulheres, sendo que diversas técnicas vêm sendo descritas para seu tratamento. OBJETIVO: Demonstrar o perfil e resultados satisfatórios da mamoplastia redutora no tratamento de hipertrofias mamárias pela classificação de Bozola. MÉTODO: Estudo descritivo e retrospectivo, com 94 pacientes submetidas àmamoplastia redutora, entre janeiro de 2011 e outubro de 2013, avaliadas segundo idade, queixa principal, comorbidades, índice de massa corporal (IMC), maternidade prévia, flacidez de pele, contorno e consistência mamária, tumorações, graus de hipertrofia submetidas à mamoplastia com a técnica de Ariê e Peixoto, com pedículo I de Lyacir Ribeiro, e a técnica de Pitanguy. No pós-operatório as pacientes foram avaliadas quanto à satisfação dos resultados observados pela simetria das mamas, tamanho, complicações e sensibilidade do complexo areolopapilar (CAP). RESULTADOS: A média de idade das pacientes foi de 28,5 anos e IMC médio de 27,66. A principal queixa foi de desconforto e quadro doloroso em 73,4%. Média de tecido total ressecado foi de 952,5 g. Foi evidenciado taxa de complicação em 27,6%. O avaliador considerou forma, simetria e sensibilidade do CAP. A satisfação, quanto ao procedimento, foi evidenciada como ótima em 51,1% dos casos, e boa em 35,1%. CONCLUSÃO: As técnicas de Ariê e Peixoto, com pedículo inferior, e de Pitanguy promoveram resultados duradouros com maior prazo de sustentação da mama, além de um polo superior medial desenhado com curvas mais acentuadas.

Introduction: In women, breast hypertrophy is a source of physical and emotional pain; several techniques have been described for its treatment. Objective: To demonstrate the appearance and satisfactory results obtained with reductive mammoplasty for the treatment of breast hypertrophy according to Bozola's classification. Method: This descriptive and retrospective study included 94 patients who underwent reductive mammoplasty between January 2011 and October 2013. The patients were evaluated according to age, chief complaint, comorbidities, body mass index (BMI), history of pregnancy, presence of sagging skin, breast contour and consistency, tumors, and hypertrophy grade. The patients underwent reductive mammoplasty using the technique of Ariê and Peixoto with the type I pedicle of Ribeiro as well as Pitanguy's method. During the postoperative period, patient satisfaction was evaluated according to the outcomes observed and regarding breast symmetry, size, complications, and nipple-areola complex (NAC) sensitivity. Results: The average patient age was 28.5 years and the average BMI was 27.66. The main complaint was discomfort and pain (73.4%). The average weight of resected tissue was 952.5 g. The occurrence of complications was observed in 27.6% of patients. For the evaluation, form, symmetry and NAC sensitivity were considered. The satisfaction rate was great in 51.1% of cases and good in 35.1%. Conclusion: The technique of Ariê and Peixoto as well as Pitanguy's method provided long-term results with durable breast support and enabled the design of a medial upper pole with more pronounced contours.

Estudo do papel dos lipídios derivados de schistosoma mansoni na ativação e polarização de macrófagos / Study of the role of lipids derived from Schistosoma mansoni in activation and polarization of macrophages

A esquistossomose mansônica, endemia parasitária típica das Américas, Ásia e África, é causada pela infecção de trematódeos da espécie Schistosoma mansoni. A infecção por este trematódeo induz no hospedeiro a formação de granulomas e uma potente polarização da resposta imune para o tipo Th2. Os helmintos podem ser apresentados em diferentes estágios do seu ciclo de vida dentro de um hospedeiro humano, e cada estágio do desenvolvimento pode apresentar diferentes combinações de glicoconjugados reconhecidos de diferentes formas pelo hospedeiro. Estudos recentes do nosso grupo demonstraram que lipídeos de S. mansoni, incluindo a lisofosfatidilcolina, possuem atividade imunomoduladora. No presente trabalho investigamos o papel imunomodulador dos lipídeos de Schistosoma mansoni, em especial a LPC, na ativação de macrófagos e os possíveis mecanismos envolvidos neste processoDemonstramos que a lisofosfatidilcolina (LPC) esquistossomal estimula a formação de corpúsculos lipídicos de forma dependente de TLR2 em macrófagos peritoneais após 24 h de estimulação in vitro, ao mesmo tempo em que induz aumento na expressão desse receptor. Entretanto, a LPC não induz aumento na produção de óxido nítrico (NO) em macrófagos, e em altas concentrações foi capaz de inibir a indução de NO gerada por LPS. Além disso, a LPC esquistossomal induziu em macrófagos um perfil de ativação do tipo M2, observado pelo aumento da expressão de arginase-1 e produção de IL-10 e PGE2. A participação do receptor nuclear PPARgama na resposta de macrófagos frente a LPC esquistossomal foi investigada. Através de diferentes técnicas demonstramos que a LPC induz aumento da expressão de PPARgama em macrófagos...

Schistosomiasis mansoni, an endemic parasitic disease typical of the Americas, Asia andAfrica, is caused by infection of trematode species of Schistosoma mansoni. The trematodeinfection in the host induces the formation of granulomas and potent polarization of Th2-typeimmune response. Helminths can be presented in different stages of their life cycle in ahuman host, and each stage of development can have different combinations of differentforms of glycoconjugates recognized by the host. Recent studies from our group demonstratedthat lipids of S. mansoni, including lysophosphatidylcholine, have immunomodulatoryactivity. In the present work, we investigated the immunomodulatory role of lipids ofSchistosoma mansoni in the activation of macrophages and the possible mechanisms involvedin this process. We demonstrated that lysophosphatidylcholine (LPC) from S. mansonistimulates the formation of lipid bodies in peritoneal macrophages in a TLR2 dependentmanner after 24 h of in vitro stimulation, while it induces increased expression of thisreceptor. However, LPC failed to induce increased production of nitric oxide (NO) inmacrophages and in high concentrations was able to inhibit the induction of NO generated byLPS. Moreover, the schistosomal-derived LPC induced in macrophages an profile of M2activation observed by increased expression of arginase-1, and production of IL-10 andPGE2. Participation of the nuclear receptor PPAR gamma in macrophage response againstLPC was investigated. Through various techniques we demonstrated that the LPC inducesincreased expression of PPAR gamma in macrophages...

Controle antidoping no Brasil: monitoramento e prática de dopagem / Doping control in Brazil: monitoring the practice of doping / Control antidopaje en Brasil: seguimiento de la práctica de dopaje

O uso de substâncias ou métodos proibidos visando melhorar o desempenho vem se tornando mais frequente no meio esportivo. Sendo assim, o objetivo desta pesquisa é caracterizar os resultados de exames antidoping realizados no Brasil no ano de 2008 em diferentes esportes. Os dados foram coletados junto ao Laboratório de Controle de Dopagem da UFRJ e Comitê Olímpico Brasileiro, ambos credenciados pelo Comitê Olímpico Internacional e pela WADA. Naquele ano foram realizados 4.621 exames, sendo 4.587 em competição e 34 fora de competição. O futebol foi a modalidade com maior índice de positividade em ambos os tipos de exames. Os avanços científicos possibilitam métodos de controle cada vez mais sofisticados na identificação do uso de drogas no esporte.

The use of substances or forbidden methods to improve the performance has become more frequent in sports. This research objective is to characterize the results of drug test accomplished in Brazil in the year of 2008. The data were obtained in the Laboratory of Drug Test of the Federal University of Rio de Janeiro and Brazilian Olympic Committee, both recognized by the International Olympic Committee aswell as by WADA. Four thousand six hundred twentyone exams were accomplished in the year of 2008. The soccer was the modality that presented more cases of doping. The scientific progresses allow more sophisticated methods to control the use of drugs in sports.

El uso de sustancias o métodos prohibidos para mejorar el rendimiento ha sido más frecuente en el deporte. El objetivo de esta investigación es caracterizar los resultados de las pruebas de dopaje realizados en Brasil en 2008. La recogida de datos sellevó a cabo en el Laboratorio de Control de Dopaje de la Universidad Federal deRio de Janeiro y el Comité Olímpico Brasileño, acreditados por el Comité Olímpico Internacional y la AMA. Se identificaron cuatro mil seiscientos veintiún exámenes en 2008. Fútbol fue el deporte con más casos de dopaje. Los avances científicos permiten métodos más sofisticados para controlar el dopaje en el deporte.