Prêmio Nobel de Medicina 2011.

No dia 03 de outubro de 2011, três pesquisadores dividiram o Prêmio Nobel. Dois deles na linha de imunidade inata, Bruce A. Beutler e Jules A. Hoffmann e um deles,  Ralph M. Steinman (falecido de câncer 3 dias antes da cerimônia do Prêmio),  na linha de imunidade adaptativa. Todos os 3 pesquisadores desenvolveram conceitos que hoje consideramos corriqueiros, mas que revolucionaram o modo como entendemos a resposta imune frente a diversas formas de agressão. A imunidade inata e a imunidade aprendida não são independentes uma da outra. Cada sistema atua em relação com o outro e influi sobre ele, direta ou indiretamente, por meio da indução de citocinas - mensageiros. Raramente um estímulo desencadeia uma só resposta. O que faz é iniciar várias, algumas das quais podem atuar conjuntamente ou ocasionalmente competir entre si (figura 1). Os vencedores do Prêmio Nobel descobriram também passos importantes das respostas imunes. No caso da imunidade inata,  eles explicitaram um dos seus mecanismos básicos que é a ligação do Lipopolissacáride (LPS) de um determinado agente infeccioso ao seu receptor - Toll-like receptor -  presente em algumas células do sistema imunológico, ativando a cascata imunológica inata (figura 2). Na resposta imune adaptativa, o falecido Dr Steinman constatou a existência  e isolou a famosa célula apresentadora de antígeno ou célula dendrítica. Esta é a célula que “processa” o antígeno e o apresenta aos linfócitos T e B ativando-os e criando a memória imunológica específica de cada indivíduo.  Estas descobertas foram determinantes para o Prêmio Nobel 2011.

Fig 1: resumo de imunidade inata e adaptativa

Fig 2: Papel dos LPS e do TLR na imunidade inata e das células dendríticas na imunidade adaptativa.

II Simpósio em Citometria de Fluxo - CPqAM/FIOCRUZ-PE

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Antioxidant supplementation for the treatment of acute lung injury: a meta-analysis

This meta-analysis was performed to evaluate the evidence  supporting  antioxidant supplementation as an adjunct therapy to prevent  oxidative damage  and  improve the clinical outcomes (mortality, length of hospital stay  and duration of mechanical ventilation).The  search strategy for  randomized controlled trials RCTs) involved the participation of two  researchers  who  independently assessed  the methodological quality of  each  full-text article  that was available  in  the PubMed,  ISI WEB of Knowledge and  ScienceDirect databases. We  extracted  110  studies from  the past  10 years, but  only 30  articles  met  the methodological criteria  (RCT,  blinded  and  statistically  significant results),  for a total of  241  animals  and 256  patients. This study found an odds ratio (OR) of 0.45 [95% confidence interval (CI): 0.26 to 0.79] for death in the experimental group compared with placebo (six trials, n = 256), an OR of 0.46 [95% CI:  0.26 to 0.87]  for  hospitalization time and an OR of 0.63 [95% CI: 0.35 to 1.12] for mechanical ventilation time between groups, Conflicting  evidence makes it impossible to recommend the routine use of antioxidant supplementation in critically ill patients.

VI Congresso Brasileiro de Células-tronco e Terapia Celular

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Congresso da Sociedade Brasileira de Imunologia

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FESBE 2011

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I São Paulo Advanced School on Redox Processes in Biomedicine

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Effect of a neonatal low-protein diet on the morphology of myotubes in culture and the expression of key proteins that regulate myogenesis in young and adult rats

To investigate the effects of a neonatal low-protein diet on the morphology of myotubes in culture and the expression of key proteins that regulate myogenesis in young and adult rats. Methods: Male Wistar rats (n = 18) were suckled by mothers fed diets containing 17% protein (controls, C) or 8% protein (undernourished, UN). All rats were fed a normal protein diet after weaning. Muscles were removed from the legs of 42-, 60- and 90-day-old rats. Muscle cells were cultured to assess cell number, morphology and the expression of major proteins involved in myogenesis (Pax7, cadherins, β1 integrin, IL-4Rα and myogenin) by western blotting. IL-4 levels in culture supernatants were measured by ELISA. Results: Offspring from mothers fed a low-protein diet showed a lower body weight gain. Cell number and myotube expansion were reduced in cultured muscle cells from UN, but the expression of myogenic marker proteins was unaltered. Conclusions:   Dietary restriction during lactation had no impact on the synthesis of myogenic marker proteins, and myocyte differentiation occurred normally in the muscles of offspring aged 42, 60 or 90 days. Nevertheless, the number and morphology of the myotubes are altered.VER ARTIGO (aqui)

Effects of nasal continuous positive airway pressure treatment on oxidative stress and adiponectin levels in obese patients with obstructive sleep apnea.

Obesity and obstructive sleep apnea (OSA) are both associated with the prevalence of major cardiovascular illnesses and certain common factors they are considered responsible for, such as stress oxidative increase, sympathetic tonus and resistance to insulin. The aim of the present study was to compare the effect of continuous positive airway pressure (CPAP) on oxidative stress and adiponectin levels in obese patients with and without OSA. Twenty-nine obese patients were categorized into 3 groups: group 1: 10 individuals without OSA (apnea-hypopnea index, AHI <or=5) who did not have OSA diagnosed at polysomnography; group 2: 10 patients with moderate to severe OSA (AHI >or=20) who did not use CPAP; group 3: 9 patients with moderate to severe OSA (AHI >or=20) who used CPAP. Group 3 showed significant differences before and after the use of CPAP, in the variables of diminished production of superoxide, and increased nitrite and nitrate synthesis and adiponectin levels. Positive correlations were seen between the AHI and the superoxide production, between the nitrite and nitrate levels and the adiponectin levels, between superoxide production and the HOMA-IR, and between AHI and the HOMA-IR. Negative correlations were found between AHI and the nitrite and nitrate levels, between the superoxide production and that of nitric oxide, between the superoxide production and the adiponectin levels, between AHI and the adiponectin levels, and between the nitrite and nitrate levels and the HOMA-IR. This study demonstrates that the use of CPAP can reverse the increased superoxide production, the diminished serum nitrite, nitrate and plasma adiponectin levels, and the metabolic changes existing in obese patients with OSA. VER (click)

Cytotoxicity of current adhesive systems: in vitro testing on cell cultures of primary murine macrophages.

The aim of this study was to evaluate, in vitro, the potential cytotoxicity of dentinal adhesives on alveolar macrophages of Wistar rats, after diffusion through dentin. The cytotoxicity of adhesives [single bond plus (SB), clearfil SE bond (CF) and Xeno V (XE)] applied to the occlusal surface of human dentin disks adapted to a dentin barrier test device were analyzed. The sets placed on a monolayer of cells were incubated for 24, 48 and 72h. Culture medium and Escherichia coli lipopolysaccharides (LPS) were used as negative and positive controls, respectively. Cellular cytotoxicity was evaluated by observing the cell survival rate (MTT assay) and nitric oxide production (NO). The data were analyzed by one-way factorial ANOVA and Tukey's and Tamhane's paired comparisons T2 (α=0.05). All the adhesive systems reduced the percentage of live cells by over 50%, compared with the control group. Within the same period of time, there was a statistically significant difference between the adhesives and LPS compared with the negative control group. SB presented a statistically significant difference between 24h and 72h, and XE between 48h and 72h. The quantity of NO produced in 24h did not differ statistically between the NC and adhesive groups. After 48h there was a significant difference between SB/CF and XE/NC. At 72h only CF showed a significant difference from each of the other groups. LPS differed statistically from all the other groups at all the evaluation times. Components of the adhesives tested may permeate the dentin in sufficient concentrations to cause death and damage to cell metabolism in the alveolar macrophages of rats, which indicates potential cytotoxicity to pulpal cells. TO SEE (click here) ou vídeo

As Imortais Células HeLa

Em 1951, uma mulher americana, afro-descendente chamada Henrietta Lacks foi ao Hospital Johns Hopkins para ser tratada de um câncer de colo  úterino. Sem que soubesse suas células  foram disponibilizados para a pesquisa científica. Apesar da cirurgia em que foi submetida e do tratamento com radioterapia, Lacks morreu mais tarde naquele ano, mas sua linhagem de células – conhecidas como HeLa (sigla criada com as iniciais do seu nome ) ainda vivem e são utilizadas em diferentes áreas na pesquisa científica.

O fato de ter permanecido tanto tempo nas pesquisas é dado à enorme longevidade das células e na facilidade de cultivo e proliferação. São chamadas também de células imortais, por se dividirem um número ilimitado de vezes in vitro, uma característica compartilhada pela maioria das células malignas. Por  estes e outros motivos, que se tornaram células padrões para muitos estudos.Em comemoração à contribuição involuntária de Lacks para a ciência, 11 de outubro foi proclamado o seu dia oficial.

O site/blog WIRED Science publicou um infográfico com as descobertas realizadas com estas células. Realmente impressionante. O que pensaria se soubesse dos avanços que trouxe para ciência? fonte: Bio Interativa

wwp2 media Ubiquitinação da RNA polimerase em células embrionárias pluripotentes de ratos

Ubiquitination and the degradation of the large subunit of RNA polymerase II, Rpb1, is not only involved in DNA damage-induced arrest but also in other transcription-obstructing events. However, the ubiquitin ligases responsible for DNA damage-independent processes in mammalian cells remain to be identified. Here, we identified Wwp2, a mouse HECT domain ubiquitin E3 ligase, as a novel ubiquitin ligase of Rpb1. We found that Wwp2 specifically interacted with mouse Rpb1 and targeted it for ubiquitination both in vitro and in vivo. Interestingly, the interaction with and ubiquitination of Rpb1 was dependent neither on its phosphorylation state nor on DNA damage. However, the enzymatic activity of Wwp2 was absolutely required for its ubiquitin modification of Rpb1. Furthermore, our study indicates that the interactionbetween Wwp2 and Rpb1 was mediated through WW domain of Wwp2 and C-terminal domain of Rpb1, respectively. Strikingly, downregulation of Wwp2 expression compromised Rpb1 ubiquitination and elevated its intracellular steady-state protein level significantly. Importantly, we identified six lysine residues in the C-terminal domain of Rpb1 as ubiquitin acceptor sites mediated by Wwp2. These results indicate that Wwp2 plays an important role in regulating expression of Rpb1 in normal physiological conditions. Ver matéria (aqui)

efeito condrogênico da BMP-2 na diferenciação de células-tronco mesenquimais humanas adultas

Articular cartilage is essential for the motion of the skeleton. However, this tissue is unable to spontaneously repair once injured, since it is avascular and aneural. Numerous repair strategies are developed, but they do not lead to a functional tissue and research into cartilage repair focuses now on tissue engineering technics. Adultmesenchymal stemcells (MSC), present in various tissues, have the potential to differentiate into chondrocytes in vitro in response to specific growth factors. The members of the transforming growth factor b, among them the bone morphogenetic protein (BMP)-2, appear very promising inducers in this context. BMP-2 favours chondrogenic expression, in particular expression of type IIB collagen, the cartilage-specific isoform of this collagen. Therefore, collagen type IIB is a good indicator of the differentiation state of MSC. However, since BMP-2 has also osteogenic properties, it is critical to differentially control chondrogenic and osteogenic properties of BMP-2 when used withMSC. Strategies for this control are presented in this review.Most likely, this is the combination of growth factors such as BMP-2 with biomaterials that will lead to the successful use of MSC for cartilage repair. VER MATERIA

Efeitos de aerossol revestidos com hidroxiapatita em células-tronco mesenquimais

The bioactive properties of hydroxyapatite (HAP) are evaluated for applications involving the enhancement of biocompatible prostheses by seeding human pluripotent mesenchymal stem cells (MSCs). The in vitro response of humanMSCs seeded on aerosol–gel HAP coatings is addressed in this work. The processing of the HAP coatings has been carried out by the aerosol–gel technique using calcium nitrate and triethylphosphate as starting precursors. The characterization of the coatings was carried out by using transmission electron microscopy, Fourier transform infrared spectroscopy, scanning electron microscopy, energy disperse X-ray microanalysis, and surface force microscopy, which confirmed the high performance of the HAP coatings. In vitro tests show that humanMSCs adhere to aerosol–gel-derived HAP coatings and show proliferation signals on these surface. VER MATERIA