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INTRODUCTION: An event of increasing interest during host-pathogen interactions is the polarization of patrolling/naive monocytes (MOs) into macrophage subsets (MФs). Therapeutic strategies aimed at modulating this event are under investigation. METHODS: This review focuses on the mechanisms of induction/development and profile of MФs polarized toward classically proinflammatory (M1) or alternatively anti-inflammatory (M2) phenotypes in response to bacteria, fungi, parasites, and viruses. RESULTS AND DISCUSSION: It highlights nuclear, cytoplasmic, and cell surface receptors (pattern recognition receptors/PPRs), microenvironmental mediators, and immune signaling. MФs polarize into phenotypes: M1 MФs, activated by IFN-γ, pathogen-associated molecular patterns (PAMPs, e.g. lipopolysaccharide) and membrane-bound PPRs ligands (TLRs/CLRs ligands); or M2 MФs, induced by interleukins (ILs-4, -10 and -13), antigen-antibody complexes, and helminth PAMPs. Polarization toward M1 and M2 profiles evolve in a pathogen-specific manner, with or without canonicity, and can vary widely. Ultimately, this can result in varying degrees of host protection or more severe disease outcome. On the one hand, the host is driving effective MФs polarization (M1 or M2); but on the other hand, microorganisms may skew the polarization through virulence factors to increase pathogenicity. Cellular/genomic reprogramming also ensures plasticity of M1/M2 phenotypes. Because modulation of polarization can occur at multiple points, new insights and emerging perspectives may have clinical implications during the inflammation-to-resolution transition; translated into practical applications as for therapeutic/vaccine design target to boost microbicidal response (M1, e.g. triggering oxidative burst) with specifics PAMPs/IFN-γ or promote tissue repair (M2, increasing arginase activity) via immunotherapy.

Monocytes are white blood cells (leukocytes) that help fight off various types of aggressive agents, including microorganisms (bacteria, fungi, viruses, and parasites), and help maintain the healthy balance of the human body. These cells differentiate into specific macrophages in tissues such as the lungs, heart, liver, skin, and brain. The present review focuses on the peculiar cellular properties that macrophages can acquire during the human immune response to infectious diseases. In this regard, it is discussed that macrophages are didactically divided into M1 and M2 subtypes. The first subtype (M1) is responsible for fighting pathogens and causing inflammation. The second subtype (M2) is mainly responsible for healing and repairing damaged tissue. Current knowledge shows that although both subtypes are involved in the same immune response aimed at protecting the human body, these M1 and M2 profiles have different characteristics that have implications for therapeutic measures such as developing specific drugs or vaccines to balance the immune response against a given pathogen and promote a complete cure of the disease. Alongside the therapeutic impacts, this review also looks at the characteristics that allow aggressive microorganisms to counteract the immune response developed by these M1 and M2 cell profiles. It highlights how exactly there can be greater protection or detriment to the human host against a given microorganism when there is a predilection to develop a more abundant immune response from one of the two profiles (M1 or M2).

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The association between death from Covid-19 and case management, especially in small and medium-sized municipalities, is still uncertain. To analyze sociodemographic, clinical, and pharmacological factors associated with death in patients with Coronavirus Disease 2019 (COVID-19), from a Brazilian referral public hospital. This is a cross-sectional study, with data from the hospital records of patients (≥ 18 years old) diagnosed with COVID-19, from March 2020 to March 2021. The sample was classified according to the clinical outcome into two groups (death and discharge), among which statistical associations were performed with the variables of interest, with a 5% significance level. Factors such as need for intensive care, use of mechanical ventilation, and total length of hospital stay was related to higher hospital mortality, as well as the permanence of changes in clinical laboratory testing, including lactic acid, D-dimer, markers of hepatic and renal function, C-Reactive protein, anemia, leukocytosis, lymphopenia, thrombocytopenia, pH, and blood oxygen saturation (SpO2) (P < 0.05). Medications used most frequently in the studied hospital for the treatment of COVID-19, such as enoxaparin, dexamethasone, ivermectin, acetylcysteine, chloroquine, and clarithromycin were correlated with morbimortality (P < 0.05). Clinical outcome was influenced by patient-related factors, such as age and comorbidities, however, therapeutic interventions and the choice of medication also impacted morbimortality. These results reinforce the need for preventive actions and adequate clinical protocols in the treatment of hospitalized COVID-19 patients.(AU)

A associação entre o óbito pela Covid-19 e o manejo dos casos, principalmente em municípios de pequeno e médio porte, ainda é incerta. Analisar os fatores sociodemográficos, clínicos e farmacológicos associados à morte em pacientes com a doença do Coronavírus 2019 (COVID-19) em um hospital público brasileiro de referência. Trata-se de um estudo transversal realizado com dados dos prontuários de pacientes (≥ 18 anos) diagnosticados com COVID-19 no período de março de 2020 a março de 2021. A amostra foi classificada de acordo com o desfecho clínico em dois grupos (óbito e alta) e foram realizados testes de associação estatística com as variáveis de interesse com nível de significância de 5%. Fatores como necessidade de terapia intensiva, uso de ventilação mecânica e tempo total de internação estiveram relacionados com maior mortalidade hospitalar, assim como a permanência de alterações nos exames laboratoriais clínicos, incluindo ácido lático, D-dímero, marcadores de função hepática e renal, proteína C reativa, anemia, leucocitose, linfopenia, trombocitopenia, pH e saturação de oxigênio no sangue (SpO2) (P < 0,05). Os medicamentos utilizados com maior frequência no hospital para o tratamento de COVID-19, como enoxaparina, dexametasona, ivermectina, acetilcisteína, cloroquina e claritromicina, foram correlacionados com morbimortalidade (P < 0,05). O desfecho clínico foi influenciado por fatores relacionados ao paciente, como idade e comorbidades, porém as intervenções terapêuticas e a escolha dos medicamentos também impactaram na morbimortalidade. Esses resultados reforçam a necessidade de ações preventivas e protocolos clínicos adequados no tratamento de pacientes hospitalizados com COVID-19.(AU)

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SUMMARY Background and aims: Mycobacterium tuberculosis (Mtb), the main causative agent of human tuberculosis (TB), remains as a serious public health problem. The innate immune response following Mtb infection plays a crucial role in preventing the onset of active TB and limiting its spread. Since phagocytes-derived reactive oxygen/nitrogen species (ROS/RNS) during the oxidative burst can fight Mtb, we hypothesized that the use of antioxidants could increase the host's susceptibility to Mtb/TB. In that way, we investigated the effects of the nitroxide Tempol, an antioxidant with superoxide dismutase-like activity, on the response of neutrophils against Mtb. Methods: Human blood-derived neutrophils were isolated from healthy volunteers and incubated with Mtb (H37Ra) at different multiplicities of infection (MOIs), in the absence or presence of Tempol. The levels of ROS in neutrophils were evaluated using the cytochrome C reduction assay (extracellular O2 •-) and luminol-(total intracellular and extracellular ROS) and isoluminol-(extracellular ROS) amplified chemiluminescence assay. The killing assay (two-step protocol) checked the mycobactericidal capacity of neutrophils, as calculated the phagocytosis (K p ) and intracellular killing (Kk) rates. Results: The levels of ROS and killing capacity in Mtb-stimulated neutrophils were significantly decreased by 450 µM Tempol (p < 0.05). Interestingly, Tempol decreased the k k of neutrophils, but did not affect their kp, demonstrating that a putative diminution in ROS levels, ultimately, affected the intracellular killing of Mtb. Conclusion: This study provides insights regarding the role of antioxidants on the neutrophil response toward Mtb, so that our findings deserve to be considered regarding further studies and clinical implications.

Contextualización y objetivos: Mycobacterium tuberculosis (Mtb), el principal agente causal de la tuberculosis humana (TB), es un grave problema de salud pública. La respuesta inmune innata desencadenada en la infección por Mtb juega un papel crucial en la prevención de la aparición de la tuberculosis activa y en la limitación de su propagación. Dado que las especies reactivas de oxígeno/nitrógeno derivadas de los fagocitos (ERO/ERN) durante el burst oxidativo pueden combatir la infección pulmonar por Mtb, planteamos la hipótesis de que el uso de antioxidantes podría aumentar la susceptibilidad del huésped humano hacia Mtb/TB. De esa manera, investigamos los efectos del nitróxido Tempol, un antioxidante con actividad similar a la superóxido dismutasa, sobre la respuesta de los neutrófilos contra Mtb. Métodos: se aislaron neutrófilos derivados de sangre humana de voluntarios sanos y se incubaron con Mtb (H37Ra) en diferentes multiplicidades de infección (MOI), en ausencia o presencia de Tempol. Los niveles de ERO en neutrófilos se evaluaron mediante el ensayo de la reducción del citocromo C (O2'- extracelular) y el ensayo de quimioluminiscencia, amplificada mediante el uso de luminol (ERO total, intracelular y extracelular) e isoluminol (ERO extracelular). La prueba de actividad microbicida (protocolo de dos pasos) verificó la capacidad micobactericida de los neutrófilos, calculando las tasas de fagocitosis (Kp) y muerte intracelular (Kk). Resultados: los niveles de ERO y la capacidad micobactericida en neutrófilos estimulados con Mtb disminuyeron significativamente en los grupos tratados con 450 µM de Tempol (p < 0,05). Curiosamente, Tempol disminuyó la tasa de muerte intracelular (Kk) en neutrófilos, pero no tuvo ningún efecto sobre la tasa de fagocitosis (Kp), lo que demuestra que una supuesta disminución en los niveles de ERO, en última instancia, afectó la destrucción intracelular de Mtb. Conclusión: este estudio proporciona información sobre el papel de los antioxidantes en la respuesta de los neutrófilos hacia Mtb, por lo que nuestros hallazgos merecen ser considerados con respecto a más estudios e implicaciones clínicas.

Contextualização e objetivos: Mycobacterium tuberculosis (Mtb), principal agente causal da tuberculose humana (TB), é um grave problema de saúde pública. A resposta imune inata desencadeada pela infecção por Mtb desempenha um papel crucial na prevenção do aparecimento da tuberculose ativa e na limitação de sua disseminação. Como as espécies reativas de oxigênio/nitrogênio derivadas de fagó-citos (ERO/ERN) durante a burst oxidativa podem combater a infecção pulmonar por Mtb, hipotetizamos que o uso de antioxidantes poderia aumentar a suscetibilidade do hospedeiro humano ao Mtb/TB. Assim, investigamos os efeitos do nitróxido de Tempol, um antioxidante com atividade semelhante a superóxido dismutase, na resposta de neutrófilos contra o Mtb. Métodos: neutrófilos derivados de sangue humano foram isolados de voluntários saudáveis e incubados com Mtb(H37Ra) em diferentes multiplicidades de infecção (MOI), na ausência ou presença de Tempol. Os níveis de ERO em neutrófilos foram avaliados por ensaio de depleção de citocromo C (O2•- extracelular) e ensaio de quimioluminescência, amplificado com luminol (ERO total, intracelular e extracelular) e isoluminol (ERO extracelular). O teste de atividade microbicida (protocolo de duas etapas) verificou a capacidade micobactericida dos neutrófilos, calculando as taxas de fagocitose (Kp) e morte intracelular (Kk). Resultados: os níveis de ERO e a capacidade micobactericida em neutrófilos estimulados por Mtb diminuíram significativamente nos grupos tratados com Tempol 450 µM (p < 0,05). Curiosamente, Tempol diminuiu a taxa de morte intracelular (Kk) em neutrófilos, mas não teve efeito sobre a taxa de fagocitose (Kp), mostrando que uma diminuição putativa nos níveis de ERO afetou a morte intracelular de Mtb. Conclusão: este estudo fornece informações sobre o papel dos antioxidantes na resposta dos neutrófilos ao Mtb, portanto, nossos achados merecem consideração para estudos adicionais e implicações clínicas.

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This study aims to evaluate the effects of photobiomodulation (PBM) on human monocytes, assessing the oxidative burst and ultimate fungicidal potential of these cells, as well as the gene expression at the mRNA level of CD68, CD80, CD163, CD204, IL-6, TNF-α and IL-10 in derived macrophages. Primary cultures of human monocytes were irradiated with an InGaAlP (660 nm)/GaAlAs (780 nm) diode laser (parameters: 40 mW, 0.04 cm2, 1 W/cm2; doses: 200, 400 and 600 J/cm2). Cells were submitted to the chemiluminescence assay, and a microbicidal activity assay against Candida albicans was performed. Reactive oxygen species (ROS) and nitric oxide (NO) production were measured, and cell viability was assessed by the exclusion method using 0.2% Trypan blue reagent. Irradiated monocytes were cultured for 72 h towards differentiation into macrophages. Total RNA was extracted, submitted to reverse transcription and real-time PCR. The results were analysed by ANOVA and the Tukey test (α = 0.05). Irradiated monocytes revealed a significant increase in their intracellular and extracellular ROS (P < 0.001). The 660 nm wavelength and 400 J/cm2 dose were the most relevant parameters (P < 0.001). The fungicidal capacity of the monocytes was shown to be greatly increased after PBM (P < 0.001). PBM increased the expression of TNF-α (P = 0.0302) and the production of NO (P < 0.05) and did not impair monocyte viability. PBM induces a pro-inflammatory Th1-driven response in monocytes and macrophages.

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RESUMO Objetivo: Nesta revisão sistemática, nós avaliamos o link entre indutores de estresse oxidativo e/ou nitrosativo (EO/EN) com atividade antifúngica, através de uma ação direta sobre a célula fúngica e/ou modulando a resposta de fagócitos contra fungos de interesse médico (incluindo Candida spp., Cryptococcus spp. e Aspergillus spp.). Ainda, foram avaliadas as implicações clínicas deste evento bioquímico, bem como as perspectivas quanto à busca por novos compostos com atividade antifúngica, principalmente, os provenientes de fonte natural e, que explorem a indução de um EO ou EN como parte de seu mecanismo de ação. Metodologia: Foram avaliados artigos, provenientes de diferentes bases de dados e publicados a qualquer período, acessados entre abril e junho de 2017, através da utilização de diferentes descritores. Resultados: Primeiramente, estabelecemos as definições de EO/EN, como sendo o aumento das concentrações de espécies reativas do oxigênio e/ou nitrogênio (ERO/ ERN) quantificado diretamente e, provenientes de fontes fúngicas mitocondriais, Reação de Fenton, retículo endoplasmático ou outras não definidas, e excedendo a capacidade de defesa antioxidante do microrganismo (avaliados por análises de perfis transcriptômicos ou proteômicos ou metabolômicos ou níveis de atividade enzimática). Este aumento de ERO/ERN causando EO/EN é definido por tempo e condições que conduzem a sinalização de apoptose ou reais danos a biomoléculas com perda de função (peroxidação lipídica ou oxidação proteica ou danos ao DNA) e, consequentemente, gerando morte fúngica ou outro efeito antifúngico associado. Portanto, 64 artigos (apenas um publicado antes do ano 2000 e 50 entre 2007-2017) abordam que a indução de EO ou EN na célula fúngica é parte do mecanismo de ação de clássicos agentes antifúngicos (22 publicações), tais como azóis (fluconazol, itraconazol e miconazol), polienos (anfotericina B [AnB]) e equinocandinas (mica-fungina), assim como tal modulação redox tem sido reportada como um importante alvo terapêutico na busca por novos e promissores compostos naturais com atividade antifúngica (32 publicações), que tem respaldo pela grande variedade de indutores que podem provir da natureza. Ainda, compostos que também induzem o burst oxidativo de fagócitos, incluindo AnB, são potencializadores do efeito antifúngico in vivo. Além do efeito antifúngico contra células planctônicas, os efeitos dos EO ou EN sobre biofilmes fúngicos, também têm sido reportados. Tem sido firmado na literatura recente um claro link entre EO ou EN e a atividade antifúngica, tanto para aqueles agentes antifúngicos já utilizados na terapêutica em humanos, quanto para possíveis candidatos a fármaco. Portanto, a indução do EO ou EN como parte do mecanismo de ação de antifúngicos demonstra ser um importante alvo terapêutico, com perspectivas favoráveis sobre os desfechos na prática clínica.

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SUMMARY Aim: In this systematic review, we evaluated the link between inducers of oxidative or nitrosative stresses (OS/NS) and antifungal activity against fungi of medical relevance (including Candida spp., Cryptococcus spp., and Aspergillus spp.), through a direct action on the fungal cell or modulating phagocyte response. Moreover, the clinical implications of this biochemical event, as well as the perspectives, were examined, highlighting the search for new compounds with antifungal activity, mainly those from natural sources and, which explores the induction of OS or NS as part of the mechanism of action. Methodology: Articles from different databases and published at any time were evaluated, between April and June 2017, and using different descriptors. Results: First, a definition of OS and NS was established in which an increase in reactive oxygen or nitrogen species (ROS/ RNS, quantified directly and from mitochondrial, Fenton reaction, endoplasmic reticulum or other fungal sources) should exceed the antioxidant defense capacity of the microorganism (evaluated by transcriptomic or proteomic or metabolomic profiles or enzyme activity levels). These events, by time and conditions delimited, can lead to the signaling of apoptosis or an actual damage toward biomolecules (lipid peroxidation or protein oxidation or DNA damage) and, consequently, they can cause cell death or other associated antifungal effect. Therefore, 64 articles were found, of these, only one was published before 2000 and 50 between 20072017, reporting the induction of OS or NS directly into the fungal cell via an increase in ROS or RNS as part of the mechanism of action of classical antifungal agents (22 publications), such as: azoles (fluconazole, itraconazole, and miconazole), polyenes (amphotericin B, [AnB]), and echinocandins (micafungin). This redox modulation has also been reported as an important therapeutic target in the search for new natural compounds with antifungal activity (32 publications), which is supported for the great variety of inducers from nature. Compounds that also induce the oxidative burst of phagocytes, including AnB, promote a combinatorial antifungal effect in vivo. In addition to the antifungal effect against plank-tonic cells, the relation between OS or NS and antifungal activity against fungal biofilms has also been reported. It has been established in the recent literature a clear link between OS or NS and antifungal effect, during the action of anti-fungal agents already used in the therapy in humans as well as for possible drug candidates. Thus, the induction of OS or NS as part of the mechanism of action proves to be an important therapeutic target with favorable perspectives on the outcomes in clinical practice.

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SUMMARY Aims: This study investigated the bioactivity of the crude leaf extract (CLE) and fractions hexane (HX) and ethyl acetate (EtOAc) from Talinum paniculatum alone and in association with fluconazole (FLC) against reference strain and clinical isolates of FLC-resistant Candida albicans. Furthermore, the antioxidant capability, chemical composition of this plant, and the effect's underlying mechanisms were evaluated. Methods: The antifungal activity was evaluated using checkerboard assay to establish the minimum inhibitory (MIC) and minimum microbicidal concen trations (MMC). During FLC and plant products challenges, the reactive oxygen species (ROS) generation (hydroxyl radicals [HO●]) were detected in C. albicans cells using the membrane-permeable fluorescent probes APF and HPF. High-performance liquid chromatography (HPLC) profile, quantitative analysis of antioxidant compounds, and free radical scavenging activity (DPPH assay) tests were performed. Results: The CLE and fractions presented outstanding antifungal activity and selectivity against C. albicans cells but had no synergistic effect's with FLC. The MIC values for CLE and its fractions against C. albicans reference strain were in the order of HX (31.25 µg ml-1) < EtOAc (62.5 μg ml-1) < CLE (500 μg ml-1), and against FLC-resistant C. albicans HX (125 μg ml-1) = EtOAc < CLE (500 μg ml-1). CLE and its fractions had more potent antifungal activities than FLC against the clinical isolates. Moreover, fungicidal effect's for these plant products were demonstrated against FLC-resistant C. albicans, which further conirmed an antifungal potential. Conversely, during association, plant products were shown to cause an increase in FLC MIC anywhere from 2- to 16-fold. FLC exposure led to an increase in the steady-state levels of ROS (HO●) in C. albicans cells. Next, we found that the increases in FLC MICs were owing to action of antioxidants containing-CLE and its fractions in preventing FLC-induced ROS-mediated growth inhibition of C. albicans. Conclusion: T. paniculatum can be a source of bioactive compounds with antifungal potential. However, because of the common use of its edible leaf, caution is advised during therapy with FLC (since it can decrease FLC susceptibility).

RESUMEN Objetivos: este estudio investigó la bioactividad del extracto de hoja en bruto (EHB) y las fracciones hexano (HX) y acetato de etilo (AcOEt) de Talinum paniculatum solo y en asociación con fluconazol (FLC) contra cepas de referencia y aislados clínicos de Candida albicans resistente a FLC. Además, evaluó la capacidad antioxidante, la composición química de esta planta y los mecanismos subyacentes del efecto fungicida. Métodos: la actividad antifúngica se evaluó mediante microdilución en caldo para establecer las concentraciones inhibitorias mínimas (CIM) y microbicidas mínimas (CMM). Durante el tratamiento con FLC y productos vegetales se detectó la generación de especies reactivas de oxígeno (ERO) (radicales hidroxilo [HO●]) en células de C. albicans utilizando las sondas fluorescentes permeables a la membrana APF y HPF. El perfil de cromatografía líquida de alta resolución (CLAR), el análisis cuantitativo de compuestos antioxidantes y el ensayo DPPH fueron evaluados. Resultados: el EHB y las fracciones presentaron una excelente actividad antifúngica y selectividad contra las células de C. albicans, pero no tuvieron efectos sinérgicos con FLC. Los valores de CIM para EHB y sus fracciones contra la cepa referencia de C. albicans fueron del orden de: HX (31,25 μg ml-1) < AcOEt (62,5 μg ml-1) < EHB (500 μg ml-1), y contra C. albicans resistente a FLC: HX (125 μg ml-1)= AcOEt < EHB (500 µg ml-1). EHB y sus fracciones fueron más potentes antifúngicos que FLC contra los aislados clínicos. Además, estos productos vegetales tienen efectos fungicidas contra C. albicans resistentes a FLC, esto conirmó el potencial antifúngico. Por el contrario, durante la asociación se demostró que los productos vegetales causan un aumento en la CIM de FLC de 2 a 16 veces. La exposición a FLC aumentó los niveles de ERO (HO●) en las células de C. albicans. Los aumentos en las CIM de FLC se debieron a la acción de los antioxidantes presentes en EHB y sus fracciones para prevenir la inhibición del crecimiento mediada por ERO inducida por FLC en C. albicans. Conclusión: T. paniculatum puede ser una fuente de compuestos bioactivos con potencial antifúngico. Sin embargo, debido al uso común de su hoja comestible, se recomienda usarla con precaución durante la terapia con FLC (ya que puede disminuir la susceptibilidad a FLC).

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SUMMARY Propose: We evaluated the antibacterial potential of the crude leaf extract (CLE) and fractions hexane (HX) and ethyl acetate (EtOAc) from Talinum paniculatum alone and in association with oxacillin (OXA) against OXA-resistant Staphylococcus aureus (ORSA, environment isolates) and OXA-sensitive S. aureus (OSSA, ATCC 25923). Furthermore, toxicity tests were performed. Methods: The antibacterial activity was evaluated through checkerboard assay (broth microdilution) to establish the minimum inhibitory (MIC) and minimum bactericidal concentrations (MBC). Toxicity test in mice was assessed. Results: The MIC values for the CLE and its fractions against ORSA and OSSA were in the order of HX (500 μg ml-1) = EtOAc < CLE (4000 μg ml-1). EtOAc and HX presented outstanding antibacterial activities against ORSA, and these fractions were bactericidal toward OSSA. Conversely, the associations between plant product (CLE, EtOAc, or HX) and OXA exhibited no synergistic effects. During these associations, there was an increase in OXA MICs anywhere from 2- to 4092-fold. The CLE presented absence of toxicity at a dose of 5 g kg-1 (in vivo). Conclusion: Although T. paniculatum be a good source of bioactive compounds with antistaphylococcal potential, the researchers should be cautious, since its edible leaf may interfere with OXA therapy (mitigating OXA-induced growth inhibition or killing of S. aureus and enhancing S. aureus resistance).

RESUMEN Propósito: evaluamos el potencial antibacteriano del extracto de hoja en bruto (EHB) y las fracciones hexano (HX) y acetato de etilo (AcOEt) de Talinum paniculatum solo y en asociación con oxacilina (OXA) contra Staphylococcus aureus resistente a OXA (ORSA, ambientales) y S. aureus sensible a OXA (OSSA, ATCC 25923). Además, se realizaron pruebas de toxicidad. Métodos: la actividad antibacteriana se evaluó mediante microdilución en caldo para establecer las concentraciones inhibitorias mínimas (CIM) y bactericidas mínimas (CBM). Se evaluó la toxicidad en ratones. Resultados: los valores de CIM para el EHB y sus fracciones contra ORSA y OSSA fueron del orden de HX (500 μg ml-1) = AcOEt < EHB (4000 μg ml-1). AcOEt y HX presentaron actividades antibacterianas sobresalientes contra ORSA, y estas fracciones fueron bactericidas hacia OSSA. Por el contrario, las asociaciones entre el producto vegetal (EHB, AcOEt o HX) y OXA no mostraron efectos sinérgicos. Durante estas asociaciones, hubo un aumento en las CIM de OXA de 2 a 4092 veces. EHB no mostró toxicidad a una dosis de 5 g kg-1. Conclusión: aunque T. paniculatum es una buena fuente de compuestos bioactivos con potencial antiestofilocócico, los investigadores deben ser cautelosos, ya que su hoja comestible puede interferir con la terapia con OXA (mitigando la inhibición del crecimiento inducida por OXA o la muerte de S. aureus y promoviendo resistencia bacteriana).

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The radish (Raphanus sativus L.) is a vegetable of the Brassicaceae family cultivated worldwide and has several medicinal properties. Its biological activities are related to various secondary metabolites present in the species, especially phenolics. Thus, the objectives of this study were the chemical analysis and evaluation of the antioxidant and antimicrobial activities of the dry extract and fractions of the fodder turnip leaves (R. sativus var. oleiferus Metzg.). Samples were analyzed by mass spectrometry and the antioxidant activity was evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical method and the reducing power method. Antimicrobial activity was determined by the agar diffusion and microdilution methods. The total phenols were concentrated in the butanol fraction (121.27 mg GAE/g) and the flavonoids were concentrated in the ethyl acetate fraction (98.02 mg EQ/g). The ethyl acetate fraction showed the best antioxidants results, with 83.45% of free radical scavenging and 11.34% of ferric ions reduction. The analysis of antimicrobial activity showed that the dry extract had the highest average zone of inhibition against Bacillus subtilis (18.67 mm). Smaller values of the minimum inhibitory concentration for Micrococcus luteus were, and the ethyl acetate fraction showed a lower minimum inhibitory concentration (0.1 mg/ml) for that microorganism. There was a strong correlation between the antioxidant activity and the content of phenols and flavonoids. The results showed the potential antioxidant and antimicrobial activities of this extract with the ethyl acetate fraction being most promising for further studies.

O rabanete(Raphanus sativus L.) é um vegetal da família Brassicaceae cultivado em todo o mundo e possui diversas propriedades medicinais. Suas atividades biológicas estão relacionadas aos vários metabólitos secundários presentes na espécie, especialmente os compostos fenólicos. Desta forma, os objetivos deste estudo foram realizar análises químicas e avaliar as atividades antioxidante e antimicrobiana do extrato seco e das frações das folhas de R. sativus var. oleiferus Metzg. As amostras foram analisadas em espectrômetro de massas e o potencial antioxidante foi avaliado pelos métodos do radical DPPH (2,2-difenil-1-picrilhidrazila) e do poder redutor. A atividade antimicrobiana foi determinada pelos métodos de difusão em ágar e da microdiluição. Observou-se que os fenóis totais se concentraram na fração butanólica (121,27 mg EAG/g), enquanto que e os teores de flavonoides concentraram-se na fração acetato de etila (98,02 mg EQ/g). A fração acetato de etila apresentou os melhores resultados antioxidantes, com porcentagem de sequestro dos radicais DPPH de 83,45% e com porcentagem de redução dos íons férrico de 11,34%. A análise da atividade antimicrobiana revelou que o extrato seco teve maior média de halos de inibição frente ao Bacillus subtilis(18,67 mm). Os menores valores da concentração inibitória mínima foram para Micrococcus luteus, sendo que a fração acetato de etila demonstrou menor concentração inibitória mínima (0,1 mg/mL) para esse micro-organismo. Houve uma forte correlação entre a atividade antioxidante e o teor de fenóis e de flavonoides. Os resultados demonstraram potenciais ações antioxidante e antimicrobiana do extrato e das frações avaliados, sendo a fração acetato de etila promissora para estudos posteriores.

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Background and aims: Lipopolysaccharide (LPS), an endotoxin, is a component of the outer membrane of Gram-negative bacteria that is able to activate the peripheral immune system, leading to changes in signalling pathways that act locally and systemically to achieve adaptive responses. Sickness behaviour is a motivational state in response to endotoxin exposure and includes depressed activity and a reduction of exploratory behaviour, potentially reorganising organism priorities to cope with infectious diseases. We hypothesised that 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol) modulates the leukocyte response to endotoxins and decreases LPS-induced sickness behaviour in mice.Methods: The effects of Tempol on LPS-induced peritonitis and the respiratory burst of neutrophils primed with LPS and triggered by phorbol 12-myristate-13-acetate (PMA) were evaluated. To evaluate the effects of Tempol on sickness behaviour, the mice were submitted to an open field and forced swim tests.Results: Tempol (50-100 µM/106 cells) decreased the respiratory burst of LPS-primed and PMA-stimulated neutrophils in vitro. In vivo, this nitroxide (30 and 100 mg/kg body weight) inhibited leukocyte migration to the peritoneal cavity after LPS administration in mice. Moreover, Tempol pretreatment (30 and 100 mg/kg body weight) before LPS administration also attenuated sickness behavioural changes.Conclusions: Together, these findings shed light on the mechanisms underlying the anti-inflammatory potential and confirm the therapeutic potential of nitroxides.

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Introdução: a orientação nutricional é de extrema importância para pacientes oncológicos, prevenindo deficiências nutricionais que podem gerar sérias complicações. Objetivo: avaliar o perfil nutricional de pacientes oncológicos. Método: estudo transversal, realizado em um centro de referência em oncologia de alfenas - MG. Para traçar o perfil nutricional de 52 pacientes oncológicos (n=52) durante o tratamento quimioterápico, foram utilizados métodos dietéticos e antropométricos (índice de massa corporal [iMc], prega cutânea tricipital [Pct], circunferência do braço [cB], circunferência muscular do braço [cMB] e percentagem da perda de peso [%PP]). dados gerais de saúde dos pacientes foram também avaliados. Resultados: Houve predominância do sexo feminino (63%), faixa etária >50 anos (40% ic95% 27-53,7). o tipo de câncer correlacionou-se ao sexo (p<0,01). no sexo feminino, o de mama teve prevalência de 51%, seguido pelo uterino (18%). no masculino, a prevalência de câncer de próstata foi de 10% e, comum aos dois sexos, o câncer de pulmão, de 15%, sendo o mais prevalente no masculino (32%). Hipertensão arterial sistêmica foi a comorbidade mais reportada (75%) e enjoos, o efeito adverso mais comum (69%). as médias dos parâmetros iMc, Pct, cB e cMB não sofreram alterações significativas (p>0,05) ao final do tratamento, mas 40% dos pacientes tiveram um grave %PP, 23% não grave %PP, 4% mantiveram o peso e 33% apresentaram ganho de peso. entre os pacientes avaliados, 48% usavam suplementos nutricionais. Conclusão: a orientação nutricional deve ser desenvolvida junto aos pacientes oncológicos, desde que se demonstrou um variado perfil nutricional em uma amostra heterogênea de pacientes

Introduction: nutritional counseling for patients with cancer is very important, because it can prevent nutritional deficiencies and other serious complications. Objective: to evaluate the nutritional profile of oncological patients. Method: cross-sectional study, carried out at a reference center in oncology, alfenas, Minas Gerais, Brazil. dietary and anthropometric methods (body mass index [BMi], triceps skinfold [ts], arm circumference [aB], arm muscle circumference [aMc], and percentage of weight loss [PWl]) were used to trace the nutritional profile of 52 oncological patients (n=52) during chemotherapy. other conditions of health were also evaluated. Results: There was a predominance of female sex (63%), and the age group >50 years (40% ci95[%] 27-53.7). The type of cancer correlated with patient's sex (p<0.01). in female sex, the breast cancer had a prevalence of 51%, followed by the uterus cancer (18%). in male sex, the prevalence of prostate cancer was 10%, and, common to both sexes, lung cancer had a prevalence of 15%, being the most prevalent in males (32%). systemic arterial hypertension was the most reported comorbidity (75%), and motion sickness the most common adverse event (69%). The mean values of the parameters BMi, ts, aB and aMc did not change significantly (p>0.05) at the end of the treatment, but 40% of the patients had a severe PWl, 23% no severe PWl, 4% kept the weight, and 33% presented weight gain. among the patients evaluated, 48% used nutritional supplements. Conclusion: nutritional counseling should be developed together with oncological patients, since we showed a variable nutritional profile in a heterogeneous sample of patients.

ntroducción: la orientación nutricional es de extrema importancia para los pacientes oncológicos, previniendo deficiencias nutricionales que pueden generar serias complicaciones. Objetivo: evaluar el perfil nutricional de 52 pacientes oncológicos. Método: estudio transversal, realizado en un centro de referencia en oncología de alfenas, Minas Gerais, Brasil. Para desenar el perfil nutricional de 52 pacientes oncológicos (n=52) durante la quimioterapia, se utilizaron métodos dietéticos y antropométricos (índice de masa corporal [iMc], pliegue cutáneo tricipital [Pct], circunferencia del brazo [cB], circunferencia muscular del brazo [cMB]) y el porcentaje de la pérdida de peso [% PP]). se evaluaron también los datos generales de salud de los pacientes. Resultados: Hubo predominancia del sexo femenino (63%), y la franja de edad >50 años (40% ic95% 27-53,7). el tipo de cáncer se correlacionó con el sexo (p<0,01). en el sexo femenino, el de mama tuvo prevalencia del 51%, seguido por el uterino (18%). Para el sexo masculino, la prevalencia de cáncer de próstata fue del 10% y, común a los dos sexos, el cáncer de pulmón tuvo una prevalencia del 15%, siendo el más prevalente el sexo masculino (32%). Hipertensión arterial sistémica fue la comorbilidad más reportada (75%), y mareo el efecto adverso más común (69%). los valores de los parámetros iMc, Pct, cB y cMB no sufrieron cambios significativos (p>0,05) al final del tratamiento, pero el 40% de los pacientes tuvieron una grave % PP, el 23% una no grave % PP, el 4% mantuvieron el peso y el 33% de los evaluados presentaron una ganancia de peso. entre los pacientes evaluados, 48% usaban suplementos nutricionales. Conclusión: la orientación nutricional debe desarrollarse junto a los pacientes oncológicos, una vez que se haya demostrado un variado perfil nutricional en una muestra heterogéneo de pacientes

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