Herpes simplex virus type 2 (HSV-2) is the most common agent of sexually transmitted infections around the world. Currently, no vaccine is available, and acyclovir is the reference compound in ...treatment HSV-2 infections. However, the emergence of resistant strains has reduced the efficacy in treatment. Several studies have shown marine seaweed biological activities, but there are no studies yet about the activity anti-HSV-2 of two its secundary metabolites, atomaric acid (1) and marine dolastane (2), isolated from Stypopodium zonale and Canistrocarpus cervicornis respectively. Therefore, we evaluated the anti-HSV-2 activity of compounds 1 and 2. Both compounds showed anti-HSV-2 activity with low cytotoxicity and compound 1 inactivated 90% of the viral particles at 50 µM. Both compounds inhibited the penetration and results in silico indicated the compound 1 as possible therapy alternative anti -HSV-2.
spp. is an important foodborne agent of salmonellosis, whose sources in humans often include products of avian origin. The control of this bacterium is difficult especially when
spp. is organized ...into biofilms. We hypothesized that the novel nanocomposites of ZnO nanocrystals doped with silver (Ag) and silver oxide (AgO) nanocrystals (ZnO:Ag-AgO) synthesized by the coprecipitation method could control or prevent the formation of
Enteritidis (SE) and
Heidelberg (SH) biofilm and its entry into turkey eggs. The diffraction characteristics of ZnO and AgO showed sizes of 28 and 30 nm, respectively. The Zn to Ag substitution into the ZnO crystalline structure was evidenced by the ionic radius of Ag+2 (1.26 Å), which is greater than Zn+2 (0.74 Å). For the SE analyses post-biofilm formation, the ZnO:Ag-AgO was not able to eliminate the biofilm, but the bacterial load was lower than that of the control group. Additionally, SE was able to infiltrate into the eggs and was found in both albumen and yolk. For the SH analyses applied onto the eggshells before biofilm formation, the ZnO:Ag-AgO treatment prevented biofilm formation, and although the bacterium infiltration into the eggs was observed in all treated groups, it was significantly smaller in ZnO:Ag-AgO pre-treated eggs, and SH could not reach the yolk. There was no difference in pore size between groups; therefore, the inhibition of biofilm formation and the prevention of bacterium entry into the egg were attributable to the use of ZnO:Ag-AgO, which was not influenced by the egg structure. Although the amount of Ag and Zn in the shell of the ZnO:Ag-AgO group was greater in relation to the control, this difference was not detected in the other egg components. In the search for new measures that are effective, safe and viable for controlling microorganisms in poultry farming, the application of a nanocomposite of Ag-doped ZnO and AgO nanocrystals appears as an alternative of great potential to prevent
sp biofilms in eggshells and other surfaces.
Chagas disease (CD), caused by the protozoan
, is a neglected tropical disease and a health problem in Latin America. Etiological treatment has limited effectiveness in chronic CD; thus, new ...therapeutic strategies are required. The practice of physical exercises has been widely advocated to improve the quality of life of CD patients. The most frequent clinical CD manifestation is the chronic indeterminate form (CIF), and the effect of physical exercises on disease progression remains unknown. Here, in a CIF model, we aimed to evaluate the effect of physical exercises on cardiac histological, parasitological, mitochondrial, and oxidative metabolism, electro and echocardiographic profiles, and immunological features. To establish a CIF model, BALB/c and C57BL/6 mice were infected with 100 and 500 trypomastigotes of the Y
strain. At 120 days postinfection (dpi), all mouse groups showed normal PR and corrected QT intervals and QRS complexes. Compared to BALB/c mice, C57BL/6 mice showed a lower parasitemia peak, mortality rate, and less intense myocarditis. Thus, C57BL/6 mice infected with 500 parasites were used for subsequent analyses. At 120 dpi, a decrease in cardiac mitochondrial oxygen consumption and an increase in reactive oxygen species (ROS) were detected. When we increased the number of analyzed mice, a reduced heart rate and slightly prolonged corrected QT intervals were detected, at 120 and 150 dpi, which were then normalized at 180 dpi, thus characterizing the CIF. Y-infected mice were subjected to an exercise program on a treadmill for 4 weeks (from 150 to 180 dpi), five times per week in a 30-60-min daily training session. At 180 dpi, no alterations were detected in cardiac mitochondrial and oxidative metabolism, which were not affected by physical exercises, although ROS production increased. At 120 and 180 dpi, comparing infected and non-infected mice, no differences were observed in the levels of plasma cytokines, indicating that a crucial biomarker of the systemic inflammatory profile was absent and not affected by exercise. Compared with sedentary mice, trained Y-infected mice showed similar parasite loads and inflammatory cells but reduced cardiac fibrosis. Therefore, our data show that physical exercises promote beneficial changes that may prevent CD progression.
Extracellular vesicles (EVs) act as cell communicators and immune response modulators and may be employed as disease biomarkers and drug delivery systems. In infectious diseases, EVs can be released ...by the pathogen itself or by the host cells (infected or uninfected), potentially impacting the outcome of the immune response and pathological processes. Chagas disease (CD) is caused by infection by the protozoan
and is the main cause of heart failure in endemic areas. This illness attracted worldwide attention due to the presence of symptomatic seropositive subjects in North America, Asia, Oceania, and Europe. In the acute phase of infection, nonspecific signs, and symptoms contribute to miss diagnosis and early etiological treatment. In this phase, the immune response is crucial for parasite control; however, parasite persistence, dysregulated immune response, and intrinsic tissue factors may contribute to the pathogenesis of chronic CD. Most seropositive subjects remain in the indeterminate chronic form, and from 30 to 40% of the subjects develop cardiac, digestive, or cardio-digestive manifestations. Identification of EVs containing
antigens suggests that these vesicles may target host cells and regulate cellular processes and the immune response by molecular mechanisms that remain to be determined. Parasite-released EVs modulate the host-parasite interplay, stimulate intracellular parasite differentiation and survival, and promote a regulatory cytokine profile in experimental models of CD. EVs derived from the parasite-cell interaction inhibit complement-mediated parasite lysis, allowing evasion. EVs released by
-infected cells also regulate surrounding cells, maintaining a proinflammatory profile. After a brief review of the basic features of EVs, the present study focuses on potential participation of
-secreted EVs in cell infection and persistence of low-grade parasite load in the chronic phase of infection. We also discuss the role of EVs in shaping the host immune response and in pathogenesis and progression of CD.
ABSTRACT Objective: to identify scientific evidence on the contribution of nurses' work to good practices in child care in the Brazilian literature. Method: integrative review of the literature, ...carried out in Latin American and Caribbean in Health Sciences Literature (LILACS), Medical Literature Analysis and Retrieval System Online (MEDLINE), Brazilian Nursing Database (BDENF), Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Scientific Electronic Library Online (SCIELO) database, from 2008 to 2018. Results: 14 complete studies were selected for interpretative analysis. Two categories allowed responding to the initial questioning of the study, namely: Nurses' contributions in child care; and Limits for the nurse's role in child care. Conclusion: evidences show the importance of nurses in child care for the promotion of comprehensive care for children and their families. However, there are socioeconomic, cultural, institutional and technical factors that hinder the nurses' performance in this setting.
RESUMO Objetivo: identificar na literatura brasileira as evidências científicas sobre a contribuição do trabalho do enfermeiro para boas práticas na puericultura. Método: revisão integrativa da literatura, realizada nas bases de dados Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Literatura Internacional em Ciências da Saúde (MEDLINE), Base de Dados de Enfermagem (BDENF), Cumulative Index to Nursing and Allied Health Literature (CINAHL) e Scientific Eletronic Library Online (SCIELO), no período de 2008 a 2018. Resultados: foram selecionados 14 estudos completos para análise interpretativa. Duas categorias permitiram responder ao questionamento inicial do estudo, a saber: Contribuições do enfermeiro na puericultura; e Limites para a atuação do enfermeiro na puericultura. Conclusão: as evidências apontam a importância do enfermeiro na puericultura para a promoção de um cuidado integral às crianças e suas famílias. Contudo, existem fatores socioeconômicos, culturais, institucionais e técnicos que dificultam a atuação do enfermeiro nesse cenário.
RESUMEN Objetivo: identificar en la literatura brasileña las evidencias científicas sobre la contribución del trabajo del enfermero a buenas prácticas en la puericultura. Método: revisión integrativa de la literatura, realizada en las bases de datos Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Medical Literature Analysis and Retrieval System Online (MEDLINE), Base de Dados de Enfermagem (BDENF), Cumulative Index to Nursing and Allied, en la base de datos bibliográfica de Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) (CINAHL) y Scientific Eletronic Library Online (SCIELO), en el período de 2008 a 2018. Resultados: se seleccionaron 14 estudios completos para análisis interpretativo. Dos categorías permitieron responder al cuestionamiento inicial del estudio, a saber: Contribuciones del enfermero en la puericultura y Límites para la actuación del enfermero en la puericultura. Conclusión: las evidencias apuntan la importancia del enfermero en la puericultura para la promoción de un cuidado integral a los niños y sus familias. Sin embargo, existen factores socioeconómicos, culturales, institucionales y técnicos que dificultan la actuación del enfermero en ese escenario.
This article provides a diversity-oriented synthesis of hydroxylated aryl-quinones via CH oxygenation reactions and their evaluation against Trypanosoma cruzi. We have identified 9 compounds more ...potent than benznidazole (Bz), among these novel arylated and hydroxylated quinones.
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•Twenty-five quinones were prepared and evaluated against Trypanosoma cruzi.•Nine compounds exhibited trypanocidal activity.•CH oxygenation reactions were used to identify new trypanocidal quinones.
A diversity-oriented synthesis of hydroxylated aryl-quinones via CH oxygenation reactions and their evaluation against Trypanosoma cruzi, the etiological agent of Chagas disease, was accomplished. With the use of ruthenium(II)- or palladium(II)-based catalysts, complementary regioselectivities were observed in the hydroxylation reactions and we have identified 9 compounds more potent than benznidazole (Bz) among these novel arylated and hydroxylated quinones. For instance, 5-hydroxy-2-4-(trifluoromethyl)phenyl-1,4-naphthoquinone (4h) with an IC50/24 h value of 22.8 µM is 4.5-fold more active than the state-of-the-art drug Bz. This article provides the first example of the application of CH activation for the position-selective hydroxylation of arylated quinones and the identification of these compounds as trypanocidal drug candidates.
Fifty-one 1,2,3-triazole derivatives were synthesized and evaluated with respect to P2X7 receptor (P2X7R) activity and its associated pore. These triazoles were screened in vitro for dye uptake assay ...and its cytotoxicity against mammalian cell types. Seven 1,2,3-triazole derivatives (5e, 6e, 8h, 9d, 9i, 11, and 12) potently blocked P2X7 receptor pore formation in vitro (J774.G8 cells and peritoneal macrophages). All blockers displayed IC50 value inferior to 500 nM, and they have low toxicity in either cell types. These seven selected triazoles inhibited P2X7R mediated interleukin-1 (IL-1β) release. In particular, compound 9d was the most potent P2X7R blocker. Additionally, in mouse acute models of inflammatory responses induced by ATP or carrageenan administration in the paw, compound 9d promoted a potent blocking response. Similarly, 9d also reduced mouse LPS-induced pleurisy cellularity. In silico predictions indicate this molecule appropriate to develop an anti-inflammatory agent when it was compared to commercial analogs. Electrophysiological studies suggest a competitive mechanism of action of 9d to block P2X7 receptor. Molecular docking was performed on the ATP binding site in order to observe the preferential interaction pose, indicating that binding mode of the 9d is by interacting its 1,2,3-triazole and ether moiety with positively charged residues and with its chlorobenzene moiety orientated toward the apolar end of the ATP binding site which are mainly composed by the Ile170, Trp167 and Leu309 residues from α subunit. These results highlight 9d derivative as a drug candidate with potential therapeutic application based on P2X7 receptor blockade.
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•Triazoles inhibit mP2X7R function in vitro.•Triazoles inhibit IL-1beta release mediated by P2X7R activation.•Triazoles inhibit hP2X7R in vitro.•Triazoles inhibit acute inflammatory response in vivo.•Triazoles potentially are competitive P2X7R antagonist.
Introdução: Aneurisma é a dilatação da parede arterial, com a presença de mudanças complexas no stress hemodinâmico e com a fragilidade do vaso, ele pode progredir para aneurisma cerebral gigante ...(ACG), cujo diâmetro é maior que 25mm. Desenvolvimento: Os ACGs têm maior efeito de massa ou isquemia cerebral, podendo apresentar crises convulsivas e maior probabilidade de rotura, evoluindo com hemorragia e déficit neurológico progressivo. Os aneurismas gigantes rotos têm maiores taxas de complicações e de mortalidade perioperatória. O tratamento padrão ouro de antigamente, clipagem cirúrgica que em reoperação pode ser associado com maiores riscos e complicações, foi substituído pela abordagem endovascular, principalmente pela embolização. Para melhor viabilização da embolização com micromolas de platina nos ACGs faz junção de técnicas com balão protetor ou com stents. Considerações finais: Dentre os tratamentos endovasculares, não há um específico que melhore o prognóstico do paciente no pós-operatório. A melhor evolução após tratamento depende da idade do paciente, do tamanho e da localização do aneurisma.
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