Placental Malaria: From Infection to Malfunction

Malaria during pregnancy is a major factor in infant morbidity and mortality. In this issue of Cell Host and Microbe, Conroy et al. (2013) propose that C5a, a product of complement cascade activation, counteracts the placental vascular remodeling response induced by Plasmodium infection and contributes to fetal growth restriction.Fundação para a Ciência e Tecnologia

Iron overload in Plasmodium berghei-infected placenta as a pathogenesis mechanism of fetal death

This deposit is composed by the main article, and it hasn't any supplementary materials associated.Plasmodium infection during gestation may lead to severe clinical manifestations including abortion, stillbirth, intrauterine growth retardation, and low birth weight. Mechanisms underlying such poor pregnancy outcomes are still unclear. In the animal model of severe placental malaria (PM), in utero fetal death frequently occurs and mothers often succumb to infection before or immediately after delivery. Plasmodium berghei-infected erythrocytes (IEs) continuously accumulate in the placenta, where they are then phagocytosed by fetal-derived placental cells, namely trophoblasts. Inside the phagosomes, disruption of IEs leads to the release of non-hemoglobin bound heme, which is subsequently catabolized by heme oxygenase-1 into carbon monoxide, biliverdin, and labile iron. Fine-tuned regulatory mechanisms operate to maintain iron homeostasis, preventing the deleterious effect of iron-induced oxidative stress. Our preliminary results demonstrate that iron overload in trophoblasts of P. berghei-infected placenta is associated with fetal death. Placentas which supported normally developing embryos showed no iron accumulation within the trophoblasts. Placentas from dead fetuses showed massive iron accumulation, which was associated with parasitic burden. Here we present preliminary data suggesting that disruption of iron homeostasis in trophoblasts during the course of PM is a consequence of heme accumulation after intense IE engulfment. We propose that iron overload in placenta is a pathogenic component of PM, contributing to fetal death. The mechanism through which it operates still needs to be elucidated.FCT: Portugal (EXPL-IMI-IMU-0428/2013), SFRH/BPD/44256/2008, SFRH/BPD/44486/2008

JURISDIÇÃO CONSTITUCIONAL NA PANDEMIA DO COVID-19: UMA INTERVENÇÃO NECESSÁRIA DO JUDICIÁRIO NA DEFESA DO DIREITO À EDUCAÇÃO PELA INCLUSÃO DIGITAL

Este artigo propõe um exame sobre o exercício da Jurisdição Constitucional aplicada às políticas públicas voltadas para a inclusão digital, no âmbito escolar, especialmente no curso da pandemia decorrente da disseminação do COVID-19. O estudo analisa que recaía também sobre o Poder Judiciário a responsabilidade de garantir que o acesso à educação fosse viabilizado por meio da ampliação e implementação de políticas públicas robustas que permitissem o acesso virtual às aulas, aos estudantes mais vulneráveis, mormente em um período em que, em nome do cumprimento da necessária medida de isolamento social, as aulas foram migradas para o modelo remoto. O estudo conclui que a intervenção do judiciário nesse tipo de hipótese seria plenamente possível pela via da Jurisdição Constitucional, mormente quando identificada a omissão dos demais poderes, legislativo e executivo, quanto à implementação dessas importantes políticas. A metodologia utilizada parte dos métodos dedutivo e indutivo, realizando a revisão da bibliografia, procurando visitar a doutrina e a legislação sobre o tema apresentado

HGF Secreted by Activated Kupffer Cells Induces Apoptosis of Plasmodium-Infected Hepatocytes

This deposit is composed by the main article plus the supplementary materials of the publicationMalaria liver stage infection is an obligatory parasite development step and represents a population bottleneck in Plasmodium infections, providing an advantageous target for blocking parasite cycle progression. Parasite development inside hepatocytes implies a gross cellular insult evoking innate host responses to counteract intra-hepatocytic infection. Using primary hepatocyte cultures, we investigated the role of Kupffer cell-derived hepatocyte growth factor (HGF) in malaria liver stage infection. We found that Kupffer cells from Plasmodium-infected livers produced high levels of HGF, which trigger apoptosis of infected hepatocytes through a mitochondrial-independent apoptosis pathway. HGF action in infected hepatocyte primary cultures results in a potent reduction of parasite yield by specifically sensitizing hepatocytes carrying established parasite exo-erythrocytic forms to undergo apoptosis. This apoptosis mechanism is distinct from cell death that is spontaneously induced in infected cultures and is governed by Fas signaling modulation through a mitochondrial-dependent apoptosis pathway. This work indicates that HGF and Fas signaling pathways are part of an orchestrated host apoptosis response that occurs during malaria liver stage infection, decreasing the success of infection of individual hepatocytes. Our results raise the hypothesis that paracrine signals derived from Kupffer cell activation are implicated in directing death of hepatocytes infected with the malaria parasite.info:eu-repo/semantics/publishedVersio

Intravital placenta imaging reveals microcirculatory dynamics impact on sequestration and phagocytosis of Plasmodium-infected erythrocytes

Malaria in pregnancy is exquisitely aggressive, causing a range of adverse maternal and fetal outcomes prominently linked to Plasmodium-infected erythrocyte cytoadherence to fetal trophoblast. To elucidate the physiopathology of infected erythrocytes (IE) sequestration in the placenta we devised an experimental system for intravital placental examination of P. berghei-infected mice. BALB/c females were mated to C57Bl/6 CFP+ male mice and infected with GFP+ P. berghei IE, and at gestational day 18, placentas were exposed for time-lapse imaging acquisition under two-photon microscopy. Real-time images and quantitative measurements revealed that trophoblast conformational changes transiently restrain blood flow in the mouse placental labyrinth. The complex dynamics of placental microcirculation promotes IE accumulation in maternal blood spaces with low blood flow and allows the establishment of stable IE-trophoblast contacts. Further, we show that the fate of sequestered IE includes engulfment by both macrophagic and trophoblastic fetal-derived cells. These findings reinforce the current paradigm that IE interact with the trophoblast and provide definitive evidence on two novel pathogenesis mechanisms: (1) trophoblast layer controls placental microcirculation promoting IE sequestration; and (2) fetal-derived placental cells engulf sequestered IE

Sustentabilidade ambiental de um sistema agroflorestal com bracatinga (Mimosa scabrella Bent.) através da analise emergética.

O sistema agroflorestal (SAF) com bracatinga (Mimosa scabrella Bent.) constitui-se em alternativa de renda e manutenção da qualidade ambiental, contribuindo para a fixação do homem no campo. A análise emergética permite a avaliação ambiental de um sistema sendo levadas em consideração todas às contribuições da natureza na sua construção. O presente estudo objetivou avaliar o desempenho ambiental de um SAF com bracatinga através do método de análise emergética. O SAF foi formado pela espécie florestal bracatinga e pelas espécies agrícolas milho e abóbora. O estudo demonstrou que os recursos naturais renováveis exercem grande participação nos fluxos emergéticos do sistema, configurando ser o maior contribuidor energético na construção do SAF de bracatinga. Dentro dos recursos da economia, a mão-de-obra familiar foi o serviço mais demandante pelo SAF, mostrando ser esse um sistema eficaz na fixação do homem no campo. O SAF com bracatinga nas condições estudadas pode ser caracterizado como sustentável em médio prazo, mas fazem-se necessários ajustes no seu atual modelo produtivo para que possa adquirir sustentabilidade em longo prazo

Placental Malaria: From Infection to Malfunction

Malaria during pregnancy is a major factor in infant morbidity and mortality. In this issue of Cell Host and Microbe, Conroy et al. (2013) propose that C5a, a product of complement cascade activation, counteracts the placental vascular remodeling response induced by Plasmodium infection and contributes to fetal growth restriction

Early exposure to distinct sources of lipids affects differently the development and hepatic inflammatory profiles of 21-day-old rat offspring

Introduction: Maternal diet composition of fatty acids during pregnancy and lactation seems to modify the fetal programming, epigenetic pattern and offspring phenotype. Aim: Herein, we investigated the effects of maternal consumption of normal-fat diets with distinct lipid sources during pregnancy and lactation on the somatic development and proinflammatory status of 21-day-old rat offspring. Materials and Methods: On the first day of pregnancy, female Wistar rats were divided into four groups as follows: soybean oil (M-SO), lard (M-L), hydrogenated vegetable fat (M-HVF) and fish oil (M-FO). Diets were maintained during pregnancy and lactation. Male offspring constituted the SO, L, HVF and FO groups. Pups were weighed and measured weekly. Lipopolysaccharide serum concentration was determined. Tumor necrosis factor alpha, interleukin (IL)-6 and IL-10 in the liver were evaluated by enzyme-linked immunosorbent assay. Liver gene expressions were determined by real-time polymerase chain reaction. Protein expressions in the liver were analyzed by Western blotting. Results: We observed an increase in body weight and adiposity in L and HVF groups. Moreover, HVF group showed an increase in the toll-like receptor 4 mRNA levels, IL10R alpha and phosphorylated form of I kappa B kinase (IKKp-IKK alpha+beta) protein expression. The FO group presented a decrease in body weight, relative weight of retroperitoneal adipose tissue, ADIPOR2 gene expression, lipopolysaccharide and p-IKK alpha+beta and phosphorylated form of nuclear transcription factor kappa B (NF kappa B) p50 (p-NF kappa B p50) protein expression. Conclusion: Summarily, whereas maternal intake of normal-fat diets based on L and HVF appear to affect the somatic development negatively, only early exposure to HVF impairs the pups' proinflammatory status. In contrast, maternal diets based on FO during pregnancy and lactation have been more beneficial to the adiposity and toll-like receptor 4 signaling pathway of the 21-day-old rat offspring, particularly when compared to L or HVF diets.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fed Univ Sao Paulo UNIFESP, PhD Program Interdisciplinar Hlth Sci, Santos, SP, BrazilFed Univ Sao Paulo UNIFESP, Discipline Nutr Physiol, Dept Physiol, Sao Paulo, SP, BrazilFed Univ Sao Paulo UNIFESP, Inst Hlth & Soc, Dept Biosci, Santos, SP, BrazilFed Univ Sao Paulo UNIFESP, PhD Program Interdisciplinar Hlth Sci, Santos, SP, BrazilFed Univ Sao Paulo UNIFESP, Discipline Nutr Physiol, Dept Physiol, Sao Paulo, SP, BrazilFed Univ Sao Paulo UNIFESP, Inst Hlth & Soc, Dept Biosci, Santos, SP, BrazilFAPESP: 2014/10683-0Web of Scienc

Bradykinin Sequestration by Plasmodium berghei Infected Erythrocytes Conditions B2R Signaling and Parasite Uptake by Fetal Trophoblasts

Plasmodium infection during pregnancy causes placental malfunction reducing fetus sustainability and leading to abortions, stillbirths, low birth weight or premature delivery. Accumulation of infected erythrocytes (IE) in the placenta is a key factor in placental malaria pathogenesis but the role played by fetal trophoblast that contact maternal blood has been neglected. Here we explore the hypothesis that interactions between Plasmodium-IE and fetal trophoblast cells impact on vasoactive alterations underlying placental dysfunction. We screened gene expression of key mediators in vasoactive pathways. We found that mRNA of bradykinin receptor 2 (B2R) and nitric oxide synthase (eNOS), as well as levels of bradykinin (BK), were decreased in late gestation placentas of pregnant Plasmodium berghei-infected mice. Co-culturing mouse trophoblasts with IE down-regulated B2R transcription and interleukin (IL)-6 secretion in a B2R-signaling dependent manner. IE showed increased levels of surface B2R and enhanced capacity to bind BK. We propose that down-regulation of B2R signaling in the course of IE–trophoblast interactions is due to BK sequestration by IE. In corroboration, levels of BK were lower in infected placentas and the positive correlation of B2R gene expression and fetal weight was disrupted by infection. This indicates that deregulation of the BK-B2R pathway is associated to placental dysfunction provoked by malaria infection. We further found that upon inhibition of B2R signaling, trophoblasts engulf IE to a lesser extent and show reduced production of IL-6. Our data suggest that BK sequestration by P. berghei represents a strategy for the parasite to ameliorate the risk of phagocytic capture by down modulating B2R activation

Comparative analysis of postural balance by posturography in patients with isolated vertigo or associated with hearing loss

Purpose: To perform a comparative analysis of the balance of subjects with isolated vertigo and dizziness associated with hearing loss. Methods: The sample consisted of 29 patients with peripheral vertigo diagnosis selected by non-probabilistic sampling and convenience aged between 45 and 64 years. The diagnostic survey to hearing evaluation consisted of audiological anamnesis and assessment of postural balance; it was made in force platform, in the bipedal and semi tandem positions with open eyes. The analyzed balance parameters were: ellipse area, center of pressure in square centimeters, average speed in centimeters per second and average frequency, in Hertz, of swaying in both directions of movement: anteroposterior and mediolateral. Results: As for the population in general, the comparison between individuals with and without hearing loss has not shown to be there any damage to the maintenance of postural balance. There was difference in women in the speed parameter in mediolateral direction. Conclusion: Although no differences have been found which might have characterized a correlation between hearing loss and balance in patients, there was a worse performance in postural balance of women with vertigo associated with hearing loss in the mediolateral parameter. Objetivo: Realizar uma análise comparativa do equilíbrio de sujeitos com vertigem isolada e com vertigem associada à perda auditiva. Métodos: A amostra foi constituída por 29 pacientes com diagnóstico de vertigem periférica, selecionados pelo método de amostragem não probabilística e por conveniência, com idade entre 45 e 64 anos, sendo 9 do gênero masculino e 20 do gênero feminino. A pesquisa diagnóstica para avaliação da audição consistiu de anamnese audiológica e audiometria tonal liminar. A avaliação do equilíbrio postural foi feita em Plataforma de Força, nas posições bipodal e semi-tandem, com os olhos abertos. Os parâmetros de equilíbrio analisados foram: área elipse, centro de pressão em centímetros quadrados, velocidade média em centímetros por segundo e frequência média, em Hertz, de oscilações do centro de pressão, em ambas as direções dos movimentos: anteroposterior e mediolateral. Resultados: Na população geral, a comparação dos dados estabilométricos entre indivíduos com e sem perda auditiva não demonstrou prejuízo da manutenção do equilíbrio postural. Houve diferença no gênero feminino, em relação ao parâmetro velocidade, na direção mediolateral. Conclusão: Embora não tenham sido encontradas diferenças que possam caracterizar correlação entre perda auditiva e equilíbrio entre os pacientes, houve pior desempenho no equilíbrio postural das mulheres com vertigem associada à perda auditiva, no parâmetro mediolateral