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The significant incidence of deforestation in South America culminates in the contact of humans with typical forests species. Among these species, one may highlight Lonomia obliqua caterpillar, which, when touched by humans, can poison them through their bristles. Therefore, better acknowledging the mechanisms involved in envenomation caused by Lonomia obliqua caterpillar bristle extract (LOCBE) may contribute to further treatments. Recently, we demonstrated that LOCBE induces a pro-inflammatory profile in endothelial cells; thus, we decided to investigate the effects of LOCBE on human polymorphonuclear neutrophils (PMN), which are the first leukocytes that migrate to the inflammatory focus. Our results showed that treatment with LOCBE induced PMN chemotaxis together with alterations in actin cytoskeleton and focal adhesion kinase (FAK) activation, favoring migration. Concurrently, LOCBE induced PMN adhesion to matrix proteins, such as collagen IV, fibronectin, and fibrinogen. Moreover, we observed that LOCBE attenuated PMN apoptosis and increased reactive oxygen species (ROS) production together with nuclear factor kB (NF-κB) activation—a redox-sensitive transcription factor—as well as interleukin (IL)-1β and IL-8 release. We call attention to the ROS-dependent effect of LOCBE on increased cell migration once an antioxidant treatment reverted it. In summary, we report that LOCBE activates PMN, inducing pro-inflammatory responses modulated by ROS.

Background: Mean platelet volume (MPV) may be a useful biomarker for platelet activation in obese patients. However, storage duration and use of anticoagulant K3-ethylenediaminetetraacetic acid (EDTA) may interfere with these measurements. Objectives: The aim of this study was to measure the variability of MPV in obese patients following exposure to EDTA. Method: A total of 160 patients were divided into 3 groups according to body mass index (BMI; normal: 2; overweight: 25–30 kg/m2; obese: >30 kg/m2). Blood was collected in sterile tubes containing K3-EDTA. Blood cell counts were obtained using the CELL-DYN Ruby system immediately and 1, 2, and 3 h after collection. Results: MPV was found to be directly proportional to BMI. With the addition of EDTA, MPV was increased in the first hour after collection; MPV then decreased to levels that were lower than initial baseline measurements. Conclusions: K3-EDTA use alters platelet volume. The time from collection to measurement should be standardized to reduce MPV value variance. MPV should be determined within 1 h of collection to avoid anticoagulant use-related interference.

The effects of angiotensin II (Ang II) on vascular smooth muscle cells (VSMC) are modulated by reactive oxygen species (ROS) and also involve integrin engagement. However, the potential link between alpha1beta1 integrin signaling with NOX system and their combined contribution to Ang II effects on VSMC have not been investigated. We aimed to elucidate the moslecular mechanisms underlying the activation of these two pathways in Ang II effects on VSMC.Ang II-induced VSMC migration (2-fold increase) and proliferation (2.5-fold increase) is modulated by alpha1beta1 integrin, being inhibited by obtustatin, a specific alpha1beta1 integrin blocker. Ang II also stimulates ROS production in VSMC (140%) that is NOX1 dependent, being completely inhibited in NOX1 silenced cells. The ROS production develops in two peaks, and the second peak is maintained by NOX2 activation. Apocynin and obtustatin inhibit the NOX2-associated second peak, but not the first peak of ROS production, which is related to NOX1 activation. Corroborating the involvement of alpha1beta1 integrin, the pretreatment of VSMC with obtustatin impaired Ang II-induced FAK phosphorylation, AKT activation, p21 degradation and the increase of ILK expression. Silencing of ILK blocked cell migration, AKT phosphorylation and the second peak of ROS, but partially inhibits (70%) VSMC proliferation induced by Ang II.The data demonstrate a novel role for NOX2 in Ang II effects on VSMC, and suggest alpha1beta1 integrin and ILK as target molecules to the development of more effective therapeutic interventions in cardiovascular diseases.

Submitted by leitem@stj.jus.br (leitem@stj.jus.br) on 2019-11-11T16:42:59Z No. of bitstreams: 2 prisao_cautelar_servidor_carreiro.pdf: 663429 bytes, checksum: 21e9453f3e09bda7fdf47f1d0d80cfa6 (MD5) license.txt: 1239 bytes, checksum: c9b4c351324448672315a00808efb725 (MD5) Approved for entry into archive by rsmoira@stj.jus.br (rsmoira@stj.jus.br) on 2019-11-12T14:59:13Z (GMT) No. of bitstreams: 2 prisao_cautelar_servidor_carreiro.pdf: 663429 bytes, checksum: 21e9453f3e09bda7fdf47f1d0d80cfa6 (MD5) license.txt: 1239 bytes, checksum: c9b4c351324448672315a00808efb725 (MD5) Made available in DSpace on 2019-11-12T14:59:13Z (GMT). No. of bitstreams: 2 prisao_cautelar_servidor_carreiro.pdf: 663429 bytes, checksum: 21e9453f3e09bda7fdf47f1d0d80cfa6 (MD5) license.txt: 1239 bytes, checksum: c9b4c351324448672315a00808efb725 (MD5) Previous issue date: 2018

O artigo busca analisar a constitucionalidade da sanção administrativa de cassação de aposentadoria do servidor público civil da União, amplamente admitida pela jurisprudência do STF. A conclusão é a de que a penalidade é incompatível com o caráter contributivo do regime previdenciário. A sanção também conflita com a natureza da sanção administrativa, desprovida de retributividade, e com a proporcionalidade, pois a eliminação da relação jurídico-previ­denciária e o confisco de longo período contributivo não são aptos para a correção ou restabelecimento da disciplina no serviço público e se mostram demasiadamente gravosos. Além disso, a privação dos meios necessários à subsistência, por evento estranho ao vínculo jurídico-previdenciário, quando o agente público se encontra em idade avançada ou permanentemente inválido, com remota possibilidade de reinserção no mercado de trabalho, ofende a dignidade da pessoa humana. A questão será definiti­vamente solucionada no julgamento da ADI nº 4882/DF.

Accumulation of vascular smooth muscle cells (VSMC) in response to inflammatory stimuli is a key event in atherogenesis, which commonly occurs in sinuous vessels with turbulent blood flow what leads to hemolysis and consequent free heme accumulation, a known pro-oxidant and pro-inflammatory molecule.In this work, we investigated the effects of free heme on VSMC, and the molecular mechanisms underlying this process.Free heme induces a concentration-dependent migration and proliferation of VSMC which depends on the production of reactive oxygen species (ROS) derived from NADPH oxidase (NADPHox) activity. Additionally, heme activates redox-sensitive proliferation-related signaling routes, such as Mitogen Activated Protein Kinase (MAPK) and NF-κB, and induces Heme Oxygenase-1 (HO-1) expression. NADPHox-dependent proliferative effect of heme seems to be endogenously modulated by HO since the pretreatment of VSMC with HO inhibitors potentiates heme-induced proliferation and, in parallel, increases ROS production. These effects were no longer observed in the presence of heme metabolites, carbon monoxide and biliverdin.The data indicate that VSMC proliferation induced by heme is endogenously modulated by a critical counter-regulatory crosstalk between NADPHox and HO systems.

Submitted by Boris INFORMAT (boris@uerj.br) on 2021-04-26T01:16:34Z No. of bitstreams: 1 Genilson Rodrigues da Silva Dissertacao completa.pdf: 1672597 bytes, checksum: 66cb07b96190475dd59335c5ea5c41fd (MD5) Made available in DSpace on 2021-04-26T01:16:34Z (GMT). No. of bitstreams: 1 Genilson Rodrigues da Silva Dissertacao completa.pdf: 1672597 bytes, checksum: 66cb07b96190475dd59335c5ea5c41fd (MD5) Previous issue date: 2016-02-02 Recently, it was demonstratedthat saliva of Lutzomyialongipalpis, main vector of leishmaniosis, presents vasoactive components such as Maxadilan (MAX), a potent vasodilator that contributes Leishmaniainfectivity. The vasoactive and pro-inflammatory effects of maxadilan are mediated by its highly selective pituitary receptor type 1 (PAC1). Recent work from our group highlights the proinflammatory actions of maxadilan, showing that this peptide increases in vivo vascular permeability and leukocytesactivation in post-capillary venules. However, the effects of MAX in endothelial cells, as well the molecular mechanisms involved in these actions are not well described. This study aims to investigate the effects of MAX on endothelial cells. First, human microvascular (HMEC-1) were incubated in the absence or presence MAX and we demonstrated that this peptideis able to increase endothelial permeability in a PAC1 -dependent manner. In addition, MAX was able to promotephosphorylation and dispersion of VE-cadherin, inducing its internalization and subsequent β-catenin nuclear translocation. Also, MAX promoted reorganization of the actin cytoskeleton, redistribution of paxillin and its colocalization with actin in the focal adhesion, Furthermore, MAX inducesFAKphosphorylation at residue 397 and its association with actin. MAX induces Srctranslocation to membrane and its association with VE-cadherin in the adherens junctions. Finally, Src inhibition reducesthe effects of MAX in the endothelial permeability. Together, our data suggest that the inflammatory events induced by MAX involve the disruption of the endothelial barrier after interaction with PAC1 receptor. A better understanding of MAX effects on endothelium may leads to the development of more specific strategies for the leishmaniosis treatment and a new tool for the study of endothelial cell biology Estudos recentes mostraram que na saliva do principal vetor da leishmaniose, o flebótomo Lutzomyialongipalpis, encontram-se componentes vasoativos, como o peptídeo maxadilan (MAX), um potente vasodilatador que contribui para infectividade de várias espécies de Leishmania. Os efeitos vasoativo e pró-inflamatório do MAX são mediados por sua ligação altamente seletiva ao receptor pituitário tipo 1 (PAC1). Trabalho recente do nosso grupo destacou a ação pró-inflamatória do MAX, mostrando que esse peptídeo induz aumento da permeabilidade vascular in vivo e ativação de leucócitos em vênulas pós-capilares. Contudo, não há na literatura relatos sobre os efeitos diretos do MAX em células endoteliais, bem como estudos sobre os mecanismos moleculares que modulariam estas ações. O presente estudo visa investigar os efeitos do MAX sobre as células endoteliais. Utilizando um modelo experimental no qual as células da microvasculatura humana (HMEC-1) foram incubadas ou não com MAX, vimos que o peptídeo foi capaz de levar aumento da permeabilidade endotelial de maneira dependente do receptor PAC1. Além disso, o peptídeo foi capaz de promover a fosforilação e dispersão de VE-caderina, induzindo sua internalização econseqüentetranslocação de β-catenina para o núcleo. O MAX promoveu reorganização do citoesqueleto de actina, fosforilação da proteína FAK no resíduo 397 e sua associação com actina, além da redistribuição de paxilina e sua colocalização com actina no ponto de adesão focal. MAX induz a translocação de Src para membrana, bem comosuacolocalização e associação com VE-caderina nas junções aderentes. Finalmente, vimos que a inibição farmacológica da proteína Src reduz o efeito de MAX no aumento na permeabilidade endotelial. Em conjunto, nossos dados sugerem que os eventos inflamatórios induzidos pelo MAX envolvem o rompimento da barreira endotelial após sua interação como receptor PAC1. Uma melhor compreensão dos efeitos do peptídeo sobre o endotélio pode conduzir ao desenvolvimento de estratégicas mais específicas para o tratamento da leishmaniose. Além disso, o MAX pode se tornar uma nova ferramenta para o estudo da biologia da célula endotelial

Background In the past decade fish farming has become an important economic activity in the Occidental Brazilian Amazon, where the number of new fish farms is rapidly increasing. One of the primary concerns with this phenomenon is the contribution of fishponds to the maintenance and increase of the anopheline mosquito population, and the subsequent increase in human malaria burden. This study reports the results of a 2-year anopheline abundance survey in fishponds and natural water bodies in a malaria-endemic area in northwest Brazil. The objective of this study was to investigate the contribution of natural water bodies (rivers, streams, creeks, ponds, and puddles) and artificial fishponds as breeding sites for Anopheles spp. in Mâncio Lima, Acre and to investigate the effect of limnological and environmental variables on Anopheles spp. larval abundance. Methods Natural water bodies and fishponds were sampled at eight different times over 2 years (early, mid and late rainy season, dry season) in the Amazonian town of Mâncio Lima, Acre. Anopheline larvae were collected with an entomological dipper, and physical, chemical and ecological characteristics of each water body were measured. Management practices of fishpond owners were ascertained with a systematic questionnaire. Results Fishponds were four times more infested with anopheline larvae than natural water bodies. Electrical conductivity and the distance to the nearest house were both significant inverse predictors of larval abundance in natural water bodies. The density of larvae in fishponds raised with increasing border vegetation. Fishponds owned by different farmers varied in the extent of anopheline larval infestation but ponds owned by the same individual had similar infestation patterns over time. Commercial fishponds were 1.7-times more infested with anopheline larvae compared to fishponds for family use. Conclusions These results suggest that fishponds are important breeding sites for anopheline larvae, and that adequate management activities, such as removal of border vegetation could reduce the abundance of mosquito larvae, most importantly Anopheles darlingi.