IL-21 treatment recovers follicular helper T cells and neutralizing antibody production in respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infections in children under 1 year. RSV vaccines are currently unavailable, and children suffering from multiple reinfections by the same viral strain fail to develop protective responses. Although RSV-specific antibodies can be detected upon infection, these have limited neutralizing capacity. Follicular helper T (Tfh) cells are specialized in providing signals to B cells and help the production and affinity maturation of antibodies, mainly via interleukin (IL) 21 secretion. In this study, we evaluated whether RSV could inhibit Tfh responses. We observed that Tfh cells fail to upregulate IL-21 production upon RSV infection. In the lungs, RSV infection downregulated the expression of IL-21/interleukin-21 receptor (IL-21R) in Tfh cells and upregulated programmed death-ligand 1 (PD-L1) expression in dendritic cells (DCs) and B cells. PD-L1 blockade during infection recovered IL-21R expression in Tfh cells and increased the secretion of IL-21 in a DC-dependent manner. IL-21 treatment decreased RSV viral load and lung inflammation, inducing the formation of tertiary lymphoid organs in the lung. It also decreased regulatory follicular T cells, and increased Tfh cells, B cells, antibody avidity and neutralization capacity, leading to an overall improved anti-RSV humoral response in infected mice. Passive immunization with purified immunoglobulin G from IL-21-treated RSV-infected mice protected against RSV infection. Our results unveil a pathway by which RSV affects Tfh cells by increasing PD-L1 expression on antigen-presenting cells, highlighting the importance of an IL-21-PD-L1 axis for the generation of protective responses to RSV infection.

Antiviral Action of Diphenyl Diselenide on Herpes Simplex Virus 2 Infection in Female BALB/c Mice.

Diphenyl diselenide, (PhSe)2 , is an organoselenium compound with pharmacological actions mostly related to antioxidant and anti-inflammatory properties. The study investigated its antiviral and virucidal actions against herpes simplex virus 2 (HSV-2) infection in vitro and in a vaginal infection model in mice. The plaque reduction assay indicated that (PhSe)2 showed virucidal and antiviral actions reducing infectivity in 70.8% and 47%, respectively. The antiviral action of (PhSe)2 against HSV-2 vaginal infection was performed by infecting mice (10(5) PFU/ml(-1) ) at day 6. The treatment with (PhSe)2 (5 mg/kg/day, intragastric [i.g.]) followed 5 days before and for more 5 days after infection. The extravaginal lesion score was evaluated from days 6 to 10. At day 11, animals were killed, and histological evaluation, determination of viral load, and TNF-α and IFN-γ levels were performed in supernatants of homogenized vaginal tissue. The levels of reactive species (RS), protein carbonyl, non-protein thiols (NPSH), nitrate/nitrite (NOx), and malondialdehyde (MDA), and the activities of myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) were determined. (PhSe)2 reduced the histological damage, extravaginal lesion scores, the viral load of vaginal tissue, and the activity of MPO, but increased the levels of TNF-α, IFN-γ. (PhSe)2 attenuated the increase of RS, MDA, NOx levels and the activity of GR caused by infection. (PhSe)2 also attenuated the reduction of NPSH content and the inhibition of CAT, SOD, and GPx activities. The antiviral action of (PhSe)2 against HSV-2 infection was related to its immunomodulatory, antioxidant, and anti-inflammatory properties. J. Cell. Biochem. 117: 1638-1648, 2016. © 2015 Wiley Periodicals, Inc.

Estimates of adherence to treatment of vivax malaria.

BACKGROUND: The relation between therapeutic failure and non-adherence to treatment of malaria has been clearly established. Several measures have been used to estimate adherence to Plasmodium vivax therapy, but few protocols have been validated to ensure reliability of the estimates of adherence. The objective of this study was to validate a five-item-reported-questionnaire derived from original Morisky four-item scale to estimate adherence to P. vivax malaria therapy. METHODS: A five-item-reported questionnaire was applied to patients after treatment of P. vivax malaria, considering behaviours regarding to forgetfulness, carelessness as to time of administration, cessation or discontinuation of use and replication of dose. Data were collected in dichotomous and Likert scales. Reliability was assessed by Cronbach's alpha and by the contribution of each item to total. The concurrent validation was done with pill count and concordance between measures of adherence by coefficient of Kappa. Sensitivity, specificity and accuracy were also determined. RESULTS: A total of 135 patients were enrolled in the study. Adherence ranged from 63.8 to 72.7% in both psychometric measures and pill count. The responses on the Likert scale showed higher proportion of non-adherence behaviour, greater variance and concordance with pill count, as well as more sensitive to characterize the behaviour of self-medication. The internal consistency of questionnaire was moderate. Significant correlations were seen with items regarding the forgiveness or careless in taking pills in all scales. The agreement between psychometric measures and pill count was considered satisfactory. The non-adherence to malaria therapy in an endemic area of Amazon basin was 33.3%. CONCLUSION: The five-item-reported questionnaire with responses on Likert scale is a feasible option for reliable estimation of adherence to malaria therapy in endemic areas.

Protective effect of brown Brazilian propolis against acute vaginal lesions caused by herpes simplex virus type 2 in mice: involvement of antioxidant and anti-inflammatory mechanisms.

Propolis has been highlighted for its antioxidant, anti-inflammatory and antiviral properties. The purpose of this study was to investigate if brown Brazilian hydroalcoholic propolis extract (HPE) protects against vaginal lesions caused by herpes simplex virus type 2 (HSV-2) in female BALB/c mice. The treatment was divided in 5 days of pre-treatment with HPE [50 mg · kg(-1), once a day, intragastric (i.g.)], HSV-2 infection [10 µl of a solution 1 × 10(2) plaque-forming unit (PFU · ml(-1) HSV-2), intravaginal inoculation at day 6] and post-treatment with HPE (50 mg · kg(-1)) for 5 days more. At day 11, the animals were killed, and the in vivo analysis (score of lesions) and ex vivo analysis [haematological and histological evaluation; superoxide dismutase (SOD), catalase (CAT) and myeloperoxidase (MPO) activities; reactive species (RS), tyrosine nitration levels, non-protein thiols (NPSH) and ascorbic acid (AA) levels] were carried out. HPE treatment reduced extravaginal lesions and the histological damage caused by HSV-2 infection in vaginal tissues of animals. HPE was able to decrease RS, tyrosine nitration, AA levels and MPO activity. Also, it protected against the inhibition of CAT activity in vaginal tissues of mice. HPE promoted protective effect on HSV-2 infected animals by acting on inflammatory and oxidative processes, and this effect probably is caused by its antioxidant and anti-inflammatory properties.

Biological detoxification of different hemicellulosic hydrolysates using Issatchenkia occidentalis CCTCC M 206097 yeast.

This work had as its main objective to contribute to the development of a biological detoxification of hemicellulose hydrolysates obtained from different biomass plants using Issatchenkia occidentalis CCTCC M 206097 yeast. Tests with hemicellulosic hydrolysate of sugarcane bagasse in different concentrations were carried out to evaluate the influence of the hydrolysate concentration on the inhibitory compounds removal from the sugarcane bagasse hydrolysate, without reduction of sugar concentration. The highest reduction values of inhibitors concentration and less sugar losses were observed when the fivefold concentrated hydrolysate was treated by the evaluated yeast. In these experiments it was found that the high sugar concentrations favored lower sugar consumption by the yeast. The highest concentration reduction of syringaldehyde (66.67%), ferulic acid (73.33%), furfural (62%), and 5-HMF (85%) was observed when the concentrated hydrolysate was detoxified by using this yeast strain after 24 h of experimentation. The results obtained in this work showed the potential of the yeast Issatchenkia occidentalis CCTCC M 206097 as detoxification agent of hemicellulosic hydrolysate of different biomass plants.

RvD1 treatment during primary infection modulates memory response increasing viral load during respiratory viral reinfection.

Resolvin D1 (RvD1), which is biosynthesized from essential long-chain fatty acids, is involved in anti-inflammatory activity and modulation of T cell response. Memory CD8+ T cells are important for controlling tumor growth and viral infections. Exacerbated inflammation has been described as impairing memory CD8+ T cell differentiation. This study aimed to verify the effects of RvD1 on memory CD8+ T cells in vitro and in vivo in a respiratory virus infection model. Peripheral blood mononuclear cells were treated at different time points with RvD1 and stimulated with anti-CD3/anti-CD28 antibodies. Pre-treatment with RvD1 increases the expansion of memory CD8+ T cells. The IL-12 level, a cytokine described to control memory CD8+ T cells, was reduced with RvD1 pre-treatment. When the mTOR axis was inhibited, the IL-12 levels were restored. In a respiratory virus infection model, Balb/c mice were treated with RvD1 before infection or after 7 days after infection. RvD1 treatment after infection increased the frequency of memory CD8+ T cells in the lung expressing II4, II10, and Ifng. During reinfection, RvD1-treated and RSV-infected mice present a high viral load in the lung and lower antibody response in the serum. Our results show that RvD1 modulates the expansion and phenotype of memory CD8+ T cells but contributed to a non-protective response after RSV reinfection.

Níveis de glutationa reduzida durante o tratamento da malária por Plasmodium vivax / Levels of reduced glutathione during the treatment of malaria by P. vivax

Objetivo: determinar os níveis de glutationa reduzida em pacientes com malária por Plasmodium vivax não complicada no decorrer do tratamento com cloroquina e primaquina. Método: estudo quantitativo longitudinal de casos em 62 sujeitos do sexo masculino com malária por Plasmodium vivax no estado do Pará de dezembro de 2010 a dezembro de 2012. A glutationa reduzida foi determinada por espectrofotometria visível, que baseou-se na sua capacidade de reduzir ácido -5,5-ditiobis-2-nitrobenzóico (DTNB) e ácido nitrobenzóico (TNB). Resultado: o nivel médio de glutationa reduzida em pacientes com malária (2,03+-1, rumol/ml) foi significativamente inferior aquele de voluntários saudáveis (3,42 +- 1,36 umol/ml). No decorrer do tratamento, houve diminuição significativa dos níveis de glutationa reduzida> Conclusão: Os níveis de glutationa reduzida em pacientes com malária por P. vivax antes da introdução da quimioterapia, foram significativamente inferiores aqueles de voluntários saudáveis pareados por idade. A administração de antimaláricos foi acompanhada pela redução dos níveis de glutationa reduzida.

Objective: determine the reduced glutathione levels in patients with uncomplicated malaria by Plasmodium vivax during the treatment with chloroquine and primaquine. Method: A longitudinal quantitative

Distribuição espacial da granulometria, cor e carbono orgânico do solo ao longo de um transecto em microbacias na Amazônia meridional / Spatial distribution of soil texture, color and soil organic carbon across a headwater transect in the southern Amazon

O objetivo deste estudo foi determinar, em nível de detalhe, a distribuição e a variabilidade espacial da argila, do índice de avermelhamento e do carbono orgânico do solo, ao longo de transecto que cruza classes pedológicas distintas dentro de quatro microbacias, sob floresta tropical em Juruena (MT). Para isso, foram selecionados 34 pontos e coletadas amostras de solo nas profundidades de 0 a 20 cm e 40 a 60 cm. Os dados foram analisados por estatística descritiva e geoestatística. As maiores variabilidades espaciais ocorreram dentro da classe do Latossolo Vermelho-Amarelo Distrófico. Estes ocorrem nas elevações superiores a 280 m, enquanto os Plintossolos e Argissolos (com caráter plíntico) têm ocorrência restrita às áreas com altimetrias menores. Ao longo do transecto há maior variabilidade nos atributos índice de avermelhamento e argila; as áreas com piores condições de drenagens apresentaram menor variação espacial e menores índice de avermelhamento, isto é, maior homogeneidade da cor dos horizontes diagnósticos.

The study was conducted in forested headwater catchments near Juruena, Mato Grosso with the objective of determining the spatial distribution of soil physical characteristics including clay content, redness ratio, and soil organic carbon along a transect that encompassed distinct soil classes. Soil samples from 0-20 cm and 40-60 cm depths were collected from 34 points. Variables were analyzed using descriptive statistics and geostatistics. The parameters analyzed by ordinary kriging demonstrated that the highest spatial variability occurred within the soil class Typic Kandiustox. In the study area, Plinthustults and Ultisols (with plinthic characteristics) were only found to occur in landscape positions less than 280 m above sea level; Oxisols were found exclusively above 280 m.a.s.l. The redness ratio and clay content were the soil parameters with the highest spatial variability across the transect. Poorly drained areas (demonstrated by lower values of redness ratio) demonstrated the lowest degree of spatial variability, and correspondingly, the highest consistency of color within the diagnostic horizons.

Dióxido de enxofre residual em camarões consumidos em Belém, Pará / Residual sulphur dioxide in shrimps from Belém, Pará

Objetivo: quantificar os teores de dióxido de enxofre residual em camarão-rosa, consumidos em Belém, no estado do Pará, a fim de verificar se as concentrações presentes encontram-se dentro dos valores recomendados pela legislação vigente. Método: estudo analítico dos teores de enxofre residual em camarões por titulação iodométrica a frio, após prévia dissolução das amostras em meio ácido. Resultados: a concentração média de dióxido de enxofre residual nas amostras deFarfantepenaeus subtilis com exoesqueleto foi 501 ±104 ppm e sem exoesqueleto de 538± 117 ppm. Não se observou diferença estatística signifcativa (p>0,05) entre os teores médios de dióxidode enxofre resídual em função do exoesqueleto. Conclusão: as amostras analisadas apresentaram teores de dióxido de enxofre residual acima do limite máximo recomendado na legislação, isto é, 100 ppm. Os resultados indicam a possibilidade da exposição humana ao dióxido de enxofre viaingestão de camarão-rosa.

Objective: To determine the residual sulphur dioxide in Farfantepenaeus subtilis samples from Belém-Pará, and determine if the levels are in agreement with the official recomendations. Method: Analysis by cold iodometric titration after acid dissolution of samples. Results: The meanconcentration of residual sulphur dioxide in Farfantepenaeus subtilis samples was 501 ±104 ppm. The samples analyzed presented residual sulphur dioxide above the limit recommended and characterize the human exposure to this compound