The Combination of Gefitinib With ATRA and ATO Induces Myeloid Differentiation in Acute Promyelocytic Leukemia Resistant Cells

In approximately 15% of patients with acute myeloid leukemia (AML), total and phosphorylated EGFR proteins have been reported to be increased compared to healthy CD34(+) samples. However, it is unclear if this subset of patients would benefit from EGFR signaling pharmacological inhibition. Pre-clinical studies on AML cells provided evidence on the pro-differentiation benefits of EGFR inhibitors when combined with ATRA or ATO in vitro. Despite the success of ATRA and ATO in the treatment of patients with acute promyelocytic leukemia (APL), therapy-associated resistance is observed in 5-10% of the cases, pointing to a clear need for new therapeutic strategies for those patients. In this context, the functional role of EGFR tyrosine-kinase inhibitors has never been evaluated in APL. Here, we investigated the EGFR pathway in primary samples along with functional in vitro and in vivo studies using several APL models. We observed that total and phosphorylated EGFR (Tyr992) was expressed in 28% and 19% of blast cells from APL patients, respectively, but not in healthy CD34(+) samples. Interestingly, the expression of the EGF was lower in APL plasma samples than in healthy controls. The EGFR ligand AREG was detected in 29% of APL patients at diagnosis, but not in control samples. In vitro, treatment with the EGFR inhibitor gefitinib (ZD1839) reduced cell proliferation and survival of NB4 (ATRA-sensitive) and NB4-R2 (ATRA-resistant) cells. Moreover, the combination of gefitinib with ATRA and ATO promoted myeloid cell differentiation in ATRA- and ATO-resistant APL cells. In vivo, the combination of gefitinib and ATRA prolonged survival compared to gefitinib- or vehicle-treated leukemic mice in a syngeneic transplantation model, while the gain in survival did not reach statistical difference compared to treatment with ATRA alone. Our results suggest that gefitinib is a potential adjuvant agent that can mitigate ATRA and ATO resistance in APL cells. Therefore, our data indicate that repurposing FDA-approved tyrosine-kinase inhibitors could provide new perspectives into combination therapy to overcome drug resistance in APL patients

Response of Benthic Foraminifera to organic matter quantity and quality and bioavailable concentrations of metals in Aveiro Lagoon (Portugal)

This work analyses the distribution of living benthic foraminiferal assemblages of surface sediments in different intertidal areas of Ria de Aveiro (Portugal), a polihaline and anthropized coastal lagoon. The relationships among foraminiferal assemblages in association with environmental parameters (temperature, salinity, Eh and pH), grain size, the quantity and quality of organic matter (enrichment in carbohydrates, proteins and lipids), pollution caused by metals, and mineralogical data are studied in an attempt to identify indicators of adaptability to environmental stress. In particular, concentrations of selected metals in the surficial sediment are investigated to assess environmental pollution levels that are further synthetically parameterised by the Pollution Load Index (PLI). The PLI variations allowed the identification of five main polluted areas. Concentrations of metals were also analysed in three extracted phases to evaluate their possible mobility, bioavailability and toxicity in the surficial sediment. Polluted sediment in the form of both organic matter and metals can be found in the most confined zones. Whereas enrichment in organic matter and related biopolymers causes an increase in foraminifera density, pollution by metals leads to a decline in foraminiferal abundance and diversity in those zones. The first situation may be justified by the existence of opportunistic species (with high reproduction rate) that can live in low oxic conditions. The second is explained by the sensitivity of some species to pressure caused by metals. The quality of the organic matter found in these places and the option of a different food source should also explain the tolerance of several species to pollution caused by metals, despite their low reproductive rate in the most polluted areas. In this study, species that are sensitive and tolerant to organic matter and metal enrichment are identified, as is the differential sensitivity/tolerance of some species to metals enrichment.CNPq [401803/2010-4]; [PEst-OE/CTE/UI4035/2014]info:eu-repo/semantics/publishedVersio

Enfermeiros e saúde pública em Belo Horizonte: combatendo doenças e educando para a saúde (1897-1933)

Este artigo analisa a organização da enfermagem na cidade de Belo Horizonte entre 1897 e 1933 - período anterior à institucionalização desse campo de saber através da criação da Escola de Enfermagem Carlos Chagas. Neste período, as ações de saúde pública estiveram principalmente voltadas ao combate e controle de epidemias e endemias e para a higiene e educação sanitária da população. Entre fins do século XIX até a década de 1910, as ações de saúde tinham na doença seu eixo de orientação e os enfermeiros realizavam atividades em hospitais de isolamento, lazaretos, hospedarias e em domicílios, sob a orientação e o acompanhamento dos médicos, ou informalmente, sem qualquer supervisão, como forma de ajuda ao próximo. As décadas de 1920 e 1930 marcam uma fase de transformações na saúde pública, com ênfase para a prevenção e a educação sanitária. A partir de então, verifica-se a organização de duas frentes de atuação de enfermeiras na prevenção e promoção da saúde: as "enfermeiras visitadoras" e as "enfermeiras escolares", cuja atividade se pautou nas orientações e práticas defendidas pelo pensamento sanitário da época. O presente estudo revela um universo em torno dos enfermeiros ainda pouco trabalhado no contexto da história da enfermagem, principalmente, no que diz respeito a essa história em Minas Gerais, com destaque à capital Belo Horizonte

SARS-CoV-2 uses CD4 to infect T helper lymphocytes

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS-CoV-2 in T helper cells. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients.</p

SARS-CoV-2 uses CD4 to infect T helper lymphocytes

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS-CoV-2 in T helper cells. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients.</p

Dynamics of biofilm formation and the interaction between Candida albicans and methicillin-susceptible (MSSA) and -resistant Staphylococcus aureus (MRSA)

Polymicrobial biofilms are an understudied and a clinically relevant problem. This study evaluates the interaction between C. albicans, and methicillin- susceptible (MSSA) and resistant (MRSA) S. aureus growing in single- and dual-species biofilms. Single and dual species adhesion (90 min) and biofilms (12, 24, and 48 h) were evaluated by complementary methods: counting colony-forming units (CFU mL-1), XTT-reduction, and crystal violet staining (CV). The secretion of hydrolytic enzymes by the 48 h biofilms was also evaluated using fluorimetric kits. Scanning electron microscopy (SEM) was used to assess biofilm structure. The results from quantification assays were compared using two-way ANOVAs with Tukey post-hoc tests, while data from enzymatic activities were analyzed by one-way Welch-ANOVA followed by Games-Howell post hoc test ( = 0.05). C. albicans, MSSA and MRSA were able to adhere and to form biofilm in both single or mixed cultures. In general, all microorganisms in both growth conditions showed a gradual increase in the number of cells and metabolic activity over time, reaching peak values between 12 h and 48 h (<0.05). C. albicans single- and dual-biofilms had significantly higher total biomass values (<0.05) than single biofilms of bacteria. Except for single MRSA biofilms, all microorganisms in both growth conditions secreted proteinase and phospholipase-C. SEM images revealed extensive adherence of bacteria to hyphal elements of C. albicans. C. albicans, MSSA, and MRSA can co-exist in biofilms without antagonism and in an apparent synergistic effect, with bacteria cells preferentially associated to C. albicans hyphal forms.CNPq (Council for Technical and Scientific Development) (Grant 400658/2012-7)Fundação para a Ciência e Tecnologia (FCT), Portugal (SFRH/BPD/71076/2010)CAPES(Coordination for the Improvement of Higher Level Personnel

Draft Genome Sequences of Salmonella enterica subsp. enterica Serovar Typhimurium Strains Isolated from Chicken and Swine Carcasses in Two Distinct Geographical Regions from Rio de Janeiro State, Brazil

Submitted by Sandra Infurna ([email protected]) on 2017-11-28T16:40:27Z No. of bitstreams: 1 phillip_suffis_etal_IOC_2017.pdf: 122087 bytes, checksum: 0c42dc4eb4a5f793547c68c77d07cf0f (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2017-11-28T17:05:24Z (GMT) No. of bitstreams: 1 phillip_suffis_etal_IOC_2017.pdf: 122087 bytes, checksum: 0c42dc4eb4a5f793547c68c77d07cf0f (MD5)Made available in DSpace on 2017-11-28T17:05:24Z (GMT). No. of bitstreams: 1 phillip_suffis_etal_IOC_2017.pdf: 122087 bytes, checksum: 0c42dc4eb4a5f793547c68c77d07cf0f (MD5) Previous issue date: 2017Universidade Federal do Rio de Janeiro. Instituto de Química. Programa de Ciência de Alimentos. Rio de Janeiro, RJ. Brasil.Universidade Federal Fluminense. Faculdade de Medicina Veterinária. Departamento de tecnologia de Alimentos. Niterói, RJ, Brasil / Universidade Severino Sombra. Faculdade de Medicina Veterinária. Vassouras, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Bioquímica e Biologia Molecular. Laboratório de Biologia Molecular e Diagnóstico de Doenças Infecciosas. Rio de Janeiro, RJ. Brasil.Universidade Federal Fluminense. Departamento de Saúde Coletiva Veterinária e Saúde Pública. Niterói, RJ, Brasil.Universidade Federal Fluminense. Faculdade de Medicina Veterinária. Departamento de tecnologia de Alimentos. Niterói, RJ, Brasil.Universidade Federal Fluminense. Departamento de Saúde Coletiva Veterinária e Saúde Pública. Niterói, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Enterobactérias. Rio de Janeiro, RJ. Brasil.Universidade Federal do Rio de Janeiro. Instituto de Química. Programa de Ciência de Alimentos. Rio de Janeiro, RJ. Brasil / Universidade Federal Fluminense. Faculdade de Medicina Veterinária. Departamento de tecnologia de Alimentos. Niterói, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Nacional de Controle de Qualidade em Saúde. Rio de Janeiro, RJ, Brasil.Salmonella enterica subsp. enterica serovar Typhimurium is a surveyed worldwide serotype with well-characterized genomes for several different strains. In Brazil, very few studies have submitted whole-genome sequences to GenBank. This genome may be useful to analyze the genetic mechanisms comparable to those of other related studies conducted in Brazil and globally