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The 1,8-naphthyridines sulfonamides are NorA efflux pump inhibitors
Get PDFThis study was financed by the Foundation for Support of Science and Technology of the State of Pernambuco (FACEPE) process number IBPG-1241-4.03/16, Financier of Studies and Projects (FINEP), National Council of Scientific and Technological Development (CNPq) process 150456/2018-2 and 406685/2018-5, and Coordination for the Improvement of Higher Education Personnel (CAPES), finance code 001.Objective: Efflux pumps are transmembrane proteins associated with bacterial resistance mechanisms. Bacteria use these proteins to actively transport antibiotics to the extracellular medium, preventing the pharmacological action of these drugs. This study aimed to evaluate in vitro the antibacterial activity of 1,8-naphthyridines sulfonamides, as well as their ability to inhibit efflux systems of Staphylococcus aureus strains expressing different levels of the NorA efflux pump. Methods: The broth microdilution test was performed to assess antibacterial activity. Efflux pump inhibition was evaluated in silico by molecular docking and in vitro by fluorometric tests, and the minimum inhibitory concentration (MIC) was determined. The MIC was determined in the association between 1,8-naphthyridine and norfloxacin or ethidium bromide. Results: The 1,8-naphthyridines did not show direct antibacterial activity. However, they effectively reduced the MIC of multidrug-resistant bacteria by associating with norfloxacin and ethidium bromide, in addition to increasing the fluorescence emission. In silico analysis addressing the binding between NorA and 1,8-naphthyridines suggests that hydrogen bonds and hydrophilic interactions represent the interactions with the most favourable binding energy, corroborating the experimental data. Conclusion: Our data suggest that 1,8-naphthyridines sulfonamides inhibit bacterial resistance through molecular mechanisms associated with inhibition of the NorA efflux pump in S. aureus strains
Auto-antibodies to type I IFNs can underlie adverse reactions to yellow fever live attenuated vaccine
No full textA vacina viva atenuada do vírus da febre amarela (YFV) pode, em casos raros, causar doença com risco de vida, geralmente em pacientes sem história prévia de doença viral grave. A deficiência completa de IFNAR1 autossômica recessiva (AR) foi relatada em um paciente de 12 anos de idade. Aqui, nós estudamos sete outros pacientes previamente saudáveis com idades entre 13 e 80 anos com doença inexplicável associada à vacina YFV com risco de vida. Um paciente de 13 anos tinha deficiência completa de IFNAR2 de AR. Três outros pacientes vacinados com idades de 47, 57 e 64 anos apresentaram altos títulos de auto-Abs circulantes contra pelo menos 14 dos 17 IFNs do tipo I individuais. Esses anticorpos foram recentemente demonstrados como subjacentes a pelo menos 10% dos casos de pneumonia COVID-19 com risco de vida. Os auto-Abs foram neutralizantes in vitro, bloqueando o efeito protetor do IFN-α2 contra cepas vacinais de YFV. A deficiência de AR IFNAR1 ou IFNAR2 e auto-Abs neutralizantes contra IFNs do tipo I foram responsáveis por mais da metade dos casos de doença associada à vacina YFV com risco de vida estudados aqui. Indivíduos previamente saudáveis podem ser testados para ambas as predisposições antes da vacinação anti-YFV.Yellow fever virus (YFV) live attenuated vaccine can, in rare cases, cause life-threatening disease, typically in patients with no previous history of severe viral illness. Autosomal recessive (AR) complete IFNAR1 deficiency was reported in one 12-yr-old patient. Here, we studied seven other previously healthy patients aged 13 to 80 yr with unexplained life-threatening YFV vaccine–associated disease. One 13-yr-old patient had AR complete IFNAR2 deficiency. Three other patients vaccinated at the ages of 47, 57, and 64 yr had high titers of circulating auto-Abs against at least 14 of the 17 individual type I IFNs. These antibodies were recently shown to underlie at least 10% of cases of life-threatening COVID-19 pneumonia. The auto-Abs were neutralizing in vitro, blocking the protective effect of IFN-α2 against YFV vaccine strains. AR IFNAR1 or IFNAR2 deficiency and neutralizing auto-Abs against type I IFNs thus accounted for more than half the cases of life-threatening YFV vaccine-associated disease studied here. Previously healthy subjects could be tested for both predispositions before anti-YFV vaccination
Health is struggle: confrontation of workers' wear by Campinas and Region metallurgists (2015-2021)
No full textA presente pesquisa trata de uma experiência de construção compartilhada de conhecimentos em saúde com participação dos operários metalúrgicos de Campinas e Região. O objetivo é estudar o enfrentamento operário e sindical ao processo de desgaste dos metalúrgicos de Campinas e Região, no âmbito das transformações produtivas e da implantação da reforma trabalhista a partir da crise econômica desencadeada no Brasil entre 2014 e 2017. Trata-se de uma pesquisa de campo cuja coleta de dados inclui a realização de entrevistas, pesquisa documental e observação participante no período de 2019-2021. Os resultados indicam o processo em curso de ofensiva do capital sobre os trabalhadores, com imposições de perdas salariais e de direitos na legislação e nas negociações coletivas, intensificação da exploração do trabalho, aumento da produtividade e demissões. Elementos que apontam para a alteração no perfil epidemiológico dos trabalhadores nos períodos subsequentes, com recrudescimento do desgaste físico e, sobretudo, mental. Principalmente a partir da reforma trabalhista de 2017, a ofensiva patronal inclui o questionamento à cláusula de estabilidade aos trabalhadores lesionados/adoecidos, com redução permanente e parcial da capacidade laboral, cuja defesa nas negociações coletivas constituiu a prioridade nas lutas do Sindicato dos Metalúrgicos de Campinas e Região. Além de defender a cláusula, a luta operária e sindical enfrenta o descumprimento da legislação de saúde e segurança do trabalho e a descaraterização da relação entre adoecimento e trabalho pelas empresas e pelo Estado. Durante a pandemia do novo coronavírus, os trabalhadores estão expostos ao contágio nas fábricas. As medidas estatais e empresariais de redução de jornada e salários e suspensão dos contratos constituem um laboratório para o desenvolvimento e aprofundamento de formas de intensificação da exploração que estão na determinação histórica e social do desgaste operário. Partindo da experiência do Sindicato, caracterizamos a saúde como luta e ressaltamos o protagonismo operário na produção de conhecimentos e luta pela saúde, bem como a centralidade da saúde operária nos conflitos entre capital e trabalho.This research approaches an experience of shared knowledge construction with participation of the Campinas and Region Metalworkers. The aim is to examine the workers and unions confrontation of Campinas and Region metalworkers’ wearing process, in the context of productive transformations and labor reform implementation, starting from the economic crisis triggered in Brazil between 2014 and 2017. The filed research techniques include interviews, documental research and participant observation in the period of 2019-2020. The results indicate the ongoing process of capital’s offensive on workers, with impositions of wage and rights’ losses in legislation and collective negotiations, intensification of labor exploitation, increased productivity and layoffs, elements that point to changes in the workers epidemiological profile in subsequent periods, with an increase in physical and, above all, mental strain. Mainly from the 2017 labor reform, employers’ offensive includes the questioning of the stability clause for injured/sick workers, with permanent and partial reduction in work capacity, whose defense constituted the priority for the Campinas and Region Metalworkers Union. Besides defending the clause, the workers and union’s struggle face the non-compliance of the legislation on health and safety at work, in addition to the mischaracterization of work-related illnesses by the companies and the State. During the new coronavirus pandemic, workers are exposed to contagion in factories, in addition to State and companies measures to reduce working hours and wages, and also suspend labor contracts, constituting a laboratory for the development and deepening of ways to intensify exploitation that are in the historical and social determination of worker’s wear. Based on the experience of the Campinas and Region Metalworkers Union, we characterize health as a struggle and emphasize the workers protagonist role in the production of knowledge and struggle for health, as well as the centrality of workers’ health in the conflicts between labor and capital
Characterization of human exposure to sewage sludge in the chain: treatment, agricultural use and consumption of vegetables
No full textObjetivou-se caracterizar a exposição humana à infecção por bactérias e vírus via ingestão, considerando os cenários: tratamento do lodo (cenário 1); uso do lodo como adubo agrícola (cenário 2) e consumo de hortaliças adubadas com lodo (cenário 3). A exposição foi caracterizada pelas concentrações de Escherichia coli, vírus entéricos cultiváveis (VEC) e colifagos somáticos (CS) nas amostras: lodo de esgoto em tratamento (LET), água de lavagem das mãos (ALM) no tratamento e no plantio, mistura solo + lodo (MSL) e hortaliças alface e cenoura. No cenário 1, em torno de 50-60 dias, as amostras LET apresentaram umidade < 10% e padrão classe A. Nas amostras LET, concentrações de CS variaram entre 9,1 × 102 e 1,9 × 105 UFP.g-1 ST e de VEC entre 2,42 e 7,15 UFP.g-1 ST. No cenário 2, CS foram detectados em 72% das amostras MSL com concentrações entre 10 e 330 UFP.mL-1. Concentrações de E. coli ≤ 102 NMP.100 mL-1 foram detectadas nas amostras ALM-tratamento (63,7%). Para vírus, todas as ALM-tratamento foram negativas e 17,4% das ALM-plantio apresentaram VEC entre 3 e 409,2 UFP.mL-1. Todas as amostras de alface foram negativas para CS e VEC. Considerando-se as características dos cenários avaliados, trabalhadores do serviço de saneamento, trabalhadores rurais e consumidores de hortaliças estiveram expostos a baixas concentrações de E. coli e VEC. CS foram resistentes ao tratamento térmico e ao plantio, o que sugere seu potencial como indicadores de VEC.The aim of this study was to characterize human exposure to microbiological contamination (bacteria and viruses) via ingestion, considering the following scenarios: treatment of sludge (scenario 1); use of sludge as fertilizer (scenario 2) and consumption of vegetables fertilized with sludge (scenario 3). Exposure was characterized by the levels of Escherichia coli, cultivable enteric viruses (CEV) and somatic coliphages (SC) in the samples: sewage sludge under treatment (SST); handwashing water (HW) in treatment and planting; mix soil + sludge (MSL) and the vegetables lettuce and carrots. In scenario 1, SST samples presented < 10% humidity and class A pattern around 50-60 days; SC concentrations ranged from 9.1 × 102 to 1.9 × 105 PFU.g-1 TS, and CEV ranged from 2.42 to 7.15 PFU.g-1 TS. In scenario 2, CS were detected in 72% of HW samples, and concentrations ranged from 10 to 330 PFU.mL-1. E. coli concentrations ≤ 102 NMP.100 mL-1 were detected in HW-treatment samples (63.7%). Viruses were not detected in 100% of HW-treatments samples, and 17.4% of HW-plantings had CEV concentrations between 3 and 409.2 PFU.mL-1. All the vegetable samples were negative for SC and CEV. Considering the characteristics of the scenarios evaluated, sewage workers, rural workers and consumers of vegetables were exposed to low concentrations of E. coli and CEV. Somatic coliphages were resistant to heat treatment and planting, which supports their potential as indicators of CE
Enhanced antibacterial effect of antibiotics by the essential oil of Aloysia gratissima (Gillies & Hook.) Tronc. and its major constituent beta-caryophyllene
No full texta Department of Biological Chemistry, Regional University of Cariri - URCA, Crato, Brazil b Maurício de Nassau College -UNINASSAU, Petrolina, PE, Brazil c Post graduate Program in Sustainable Territorial Development, Federal University of Parana ´ – UFPR, Matinhos, Brazil d Post graduate Program in Agronomy, Federal University of Parana ´ - UFPR, Curitiba, Brazil e Department of Molecular Biology, Federal University of Paraiba-UFPB, Joao ˜ Pessoa 58051-900, PB, Brazil f Departmen of Pharmacy, Federal University of Paraiba-UFPB, Joao ˜ Pessoa 58051-900, PB, Brazil g Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador, BA, BrazilAloysia gratissima (Verbenaceae), popularly known as bee-brush or whitebrush, has been widely
used in Brazilian folk medicine as analgesic, expectorant and antimicrobial. Phytochemical studies have identified
β-caryophyllene as one of the major components of the essential oil of this plant. This bioactive sesquiterpene
has been shown to have anti-inflammatory and antibacterial activities.
Purpose: The present study aimed to characterize the chemical profile and evaluate the antibacterial and
antibiotic-enhancing activities of the essential oil obtained from Aloysia gratíssima (EOAG) and β-caryophyllene.
Methods: The phytochemical analysis was performed by gas chromatography coupled to mass spectrometry (GCMS).
The antibacterial activity against Pseudomonas aeruginosa 24, Staphylococcus aureus 10, and Escherichia coli
06 was assessed by determining the minimum inhibitory concentration (MIC) using the broth microdilution
method. The potentiation of the antibiotic activity by the EOAG and the β-caryophyllene was performed using
the MIC evaluation of the antibiotic alone or in association with the essential oil and its main compound. To
evaluate the minimum reduction of the drug concentration necessary, the Dose Reduction Index (DRI) was
calculated.
Results: A reduction in the MIC of the antibiotics against strains treated simultaneously with the essential oil or
β-caryophyllene was observed. The GC-MS analysis of the EOAG identified 30 compounds, including β-caryophyllene
as the major component. Both OEAG and β-caryophyllene presented antibacterial activity against
S. aureus, in addition to potentiating the action of norfloxacin against S. aureus, P. aeruginosa, and E. coli.
Conclusions: These substances also reversed the antibiotic resistance to gentamicin and erythromycin against of
S. aureus and P. aeruginosa, respectively
Introducción al campo de la literacia en salud: concepto, usos y reflexiones para la salud pública
No full textObra resenhada: PERES, Frederico; RODRIGUES, Karla Meneses; SILVA, Thais Lacerda e. Literacia em saúde. Rio de Janeiro: Editora Fiocruz, 2021. (Temas em Saúde). ISBN: 978-65-5708-033-7. e-ISBN: 978-65-5708-106-8.Como indivíduos buscam, avaliam, compreendem e utilizam informação sobre saúde? O livro Literacia em saúde oferece possíveis respostas e outras reflexões sobre essa questão. Literacia em saúde pode ser entendida como o conjunto de habilidades e competências acionado por indivíduos e coletividades para buscar, selecionar e dar significado às informações sobre saúde. Nessa perspectiva, o livro em questão discute as relações que se configuram entre a literacia em saúde e as possibilidades de uso das informações em saúde no cuidado próprio e do outro, além de apontar possíveis aplicações na estruturação de políticas públicas e no cotidiano do sistema de saúde e estabelecer um diálogo com a pandemia de Covid-19 em curso.Programa Fiocruz de Fomento à Inovação (Inova Fiocruz) / Fundação Oswaldo CruzHow do individuals seek, assess, understand, and use health information? The book Health Literacy offers possible answers and other reflections on this issue. Health literacy can be understood as the set of skills and competences used by individuals and communities to seek, select, and give meaning to health information. From this perspective, the book discusses the relationships established between health literacy and the possibilities of using health information in the care of oneself and the other, in addition to pointing out possible applications of in the structuring of public policies and in the daily life of the health system and establishing a dialogue with the ongoing Covid-19 pandemic.¿Cómo buscan, evalúan, comprenden y utilizan las personas la información sanitaria? El libro Alfabetización en salud ofrece posibles respuestas y otras reflexiones sobre este tema. La alfabetización en salud puede entenderse como el conjunto de habilidades y competencias que utilizan los individuos y las comunidades para buscar, seleccionar y dar sentido a la información sanitaria. Desde esta perspectiva, el libro analiza las relaciones entre la alfabetización en salud y las posibilidades de utilizar la información en salud en el cuidado, además de señalar posibles aplicaciones en la estructuración de políticas públicas y en la vida diaria del sistema de salud y entablar un diálogo con la pandemia de Covid-19
The use of masks to reduce COVID-19 transmission: integrative review
No full textObjetivo: apresentar as evidências sobre o uso de máscaras por
profissionais da saúde e pela a população em geral para a proteção
contra a COVID-19.
Método: trata-se de uma revisão integrativa utilizando 5 bases biblio‑
gráficas, além de busca manual.
Resultados: Das 630 publicações identificadas, foram incluídas 32.
Todas as máscaras (respiradores, máscaras cirúrgicas e de tecido)
oferecem alguma proteção contra a COVID-19.
Conclusão: são necessárias medidas adicionais, como o distanciamen‑
to social e físico, etiqueta respiratória e higiene das mãos. Estratégias
e ações de educação voltadas ao uso e reuso adequados das máscaras,
bem como os riscos e cuidados quanto à auto-infecção.Objective: to present evidence about the use of masks by health profes‑
sionals and the general population to protect against COVID-19.
Method: It is an integrative review using 5 bibliographic bases, in addi‑
tion to manual search.
Results: Of the 630 publications identified, 32 were included. All
masks (respirators, surgical and tissue masks) offer some protection
against a COVID-19.
Conclusion: additional measures are necessary, such as social and
physical distance, respiratory etiquette and hand hygiene. Education
actions aimed at the proper use and reuse of masks are mandatory, as
well as the risks and precautions regarding self-infection
Propagação in vitro e produção de cepa transgênica de Mycobacterium leprae em linhagem IDE8 de Ixodes scapularis
No full textA hanseníase é uma doença infecciosa crônica, causada pelo Mycobacterium leprae, bacilo intracelular que infecta principalmente macrófagos da pele e células de Schwann nos nervos periféricos. A Hanseníase representa um problema de saúde pública no Brasil, por apresentar uma alta prevalência. A impossibilidade do seu cultivo in vitro até o momento torna análises fundamentais como a determinação da sensibilidade do bacilo a novos antibióticos em tarefas árduas, pois o método atual de cultivo baseia-se na infecção de camundongos atímicos estéreis, consistindo em um procedimento caro, demorado, impreciso, que demanda grandes quantidades de moléculas candidatas, realizado através do custo de vidas animais e não aplicável em protocolos de transformação. Nosso grupo demonstrou que carrapatos da espécie Amblyomma cajennense, em condições controladas, podem atuar na transmissão do M. leprae, indicando potencialidade em linhagens de células de carrapato no cultivo desse bacilo in vitro. Nossos dados demonstram que o M. leprae não só é capaz de infectar com sucesso inúmeras linhagens de células de carrapatos, como de se multiplicar in vitro no interior de ao menos uma delas, a linhagem IDE8, originária de embriões de Ixodes scapularis Através dessa linhagem de células foi possível transformar um isolado clínico do bacilo, tornando-o fluorescente através da expressão da proteína fluorescente Cherry. Através da criação de cepas de M. leprae transformadas seremos capazes de monitorar a viabilidade e a taxa metabólica do patógeno in vivo. Este trabalho aponta para o grande potencial do uso das linhagens de células de carrapatos como método de cultivo in vitro do M. leprae e a partir dessa nova metodologia a possibilidade de desenvolvimento de novas abordagens e ferramentas para estudo da hanseníase como testes mais econômicos, rápidos e precisos para a identificação de novas drogas para o controle da doençaLeprosy is a chronic infectious disease caused by Mycobacterium leprae, an intracellular bacillus that mainly infects skin macrophages and Schwann cells in peripheral nerves. Leprosy represents a public health problem in Brazil, due to its high prevalence. The impossibility of its in vitro cultivation so far makes fundamental analyzes such as determining the sensitivity of the bacillus to new antibiotics in arduous tasks, as the current method of cultivation is based on the infection of sterile athymic mice, consisting of an expensive and time-consuming procedure , imprecise, which demands large amounts of candidate molecules, carried out at the cost of animal lives and not applicable to transformation protocols. Our group demonstrated that ticks of the species Amblyomma cajennense, under controlled conditions, could act in the transmission of M. leprae, indicating potential in tick cell lines in the cultivation of this bacillus in vitro. Our data demonstrate that M. leprae is not only able to successfully infect tick cell lines, but also to multiply in vitro within at least one of them, the IDE8 lineage, originating from Ixodes scapularis embryos. Through this cell line, it was possible to transform a clinical isolate of the bacillus, making it fluorescent through the expression of the fluorescent protein Cherry. By creating transformed strains of M. leprae we will be able to monitor the pathogen's viability and metabolic rate in vivo. This work points to the great potential of using tick cell lines as a method of in vitro cultivation of M. leprae and from this new methodology the possibility of developing new approaches and tools for the study of leprosy as faster, faster tests and accurate for identifying new drugs to control the diseas
Radar Covid-19: favelas: edição 11
No full textMovimentos Sociais e coletivos: Articulação de Mulheres Brasileiras (AMBRio), Coletivo Manguinhos Cria, Conselho Comunitário de Manguinhos, Grupo de Estudos Integrais Demétrius, Instituto Socioeducativo Reaprender, Movimento Negro Unificado (MNU Vila Kennedy/Nova Iguaçu), Painel Unificador Covid-19 nas Favelas; Revisão: Fábio Araújo, José Leonídio Madureira, Luiza Gomes Henriques; Projeto Gráfico e Diagramação: Mariane MartinsRadar COVID-19 Favelas é um informativo produzido no âmbito da Sala de Situação Covid-19 nas Favelas do Rio de Janeiro, vinculada ao Observatório COVID-19 da Fiocruz. Estruturado
com base no monitoramento ativo (vigilância de rumores) de fontes não oficiais – mídias, redes sociais e contato direto com moradores, coletivos, movimentos sociais, instituições e articuladores locais – busca sistematizar, analisar e disseminar informações sobre a situação de saúde nos territórios
selecionados, visando promover a visibilidade das diversas situações de vulnerabilidade e antecipar as iniciativas de enfrentamento da pandemia
Clinical Characteristics and Mortality Profile of COVID-19 Patients Aged less than 20 years Old in Pernambuco – Brazil
No full textCOVID-19 in children and adolescents has low frequency, severity, and fatality rate all over the world. A cross-sectional study was conducted to assess the epidemiological and clinical aspects of COVID-19 in patients younger than 20 years in Pernambuco (Brazil), with cases confirmed by reverse-transcriptase-PCR SARS-CoV-2 between 13 February and June 19, 2020, reported on information systems. Data regarding age (< 30 days, 1-11 months, 1-4 years, 5-9 years, 10-14 years, and 15-19 years), gender, color/race, symptoms, pregnancy or puerperium, comorbidities, hospitalization, and death were investigated. Fatality rate and mortality coefficient were calculated, and a multiple logistic regression analysis was performed to determine if gender, age, and comorbidities were factors associated with death. Of 682 pediatric cases, 52.8% were female, with a mean age of 9 ± 7.2 years. The most frequent symptoms were fever (64.4%), cough (52.4%), and respiratory distress (32.4%). Hospitalization was reported in 46.2% of cases, mainly among neonates (80.3%) and infants (73.8%). Thirty-eight deaths were notified, and a fatality rate of 5.6% (95% CI: 3.9-7.3) was found, with higher fatality rates among neonates 11.5% (7 of 61) and 9.5% (8 of 84) infants. The mortality coefficient was 10.9 per 100,000 inhabitants < 1 year of age, whereas comorbidities (Odds ratio [OR] = 14.13, 95% CI: 6.35-31.44), age < 30 days (OR = 5.17, 95% CI: 1.81-14.77), and age 1-11 months (OR = 3.28, 95% CI: 1.21-8.91) were independent factors associated with death. The results demonstrate the vulnerability of neonates and infants with severe conditions, need hospitalization, and high fatality rate, indicating the necessity to adapt public health policies for these age-groups.2030-02-1