Activation of Toll-like receptors (TLR) induces gene expression of proteins involved in the immune system response. TLR4 has been implicated in the development and progression of cardiovascular diseases. Innate and adaptive immunity contribute to hypertension-associated end-organ damage, although the mechanism by which this occurs remains unclear. In the present study we hypothesize that inhibition of TLR4 decreases blood pressure and improves vascular contractility in resistance arteries from spontaneously hypertensive rats (SHR). TLR4 protein expression in mesenteric resistance arteries was higher in 15 weeks-old SHR than in same age Wistar controls or in 5 weeks-old SHR. In order to decrease activation of TLR4, 15 weeks-old SHR and Wistar rats were treated with anti-TLR4 antibody or non-specific IgG control antibody for 15 days (1µg per day, i.p.). Treatment with anti-TLR4 decreased mean arterial pressure as well as TLR4 protein expression in mesenteric resistance arteries and interleukin-6 (IL-6) serum levels from SHR when compared to SHR treated with IgG. No changes in these parameters were found in Wistar treated rats. Mesenteric resistance arteries from anti-TLR4-treated SHR exhibited decreased maximal contractile response to noradrenaline compared to IgG-treated-SHR. Inhibition of cyclooxygenase-1 (Cox) and Cox-2, enzymes related to inflammatory pathways, decreased noradrenaline responses only in mesenteric resistance arteries of SHR treated with IgG. Cox-2 expression and thromboxane A2 release were decreased in SHR treated with anti-TLR4 compared with IgG-treated-SHR. Our results suggest that TLR4 activation contributes to increased blood pressure, low grade inflammation and plays a role in the augmented vascular contractility displayed by SHR.

We developed two models of sepsis with different degrees of severity, sublethal and lethal sepsis, induced by cecal ligation and puncture. Lethal sepsis induced by cecal ligation and puncture (L-CLP) resulted in failure of neutrophil migration to the infection site and high mortality. Treatment of septic animals with aminoguanidine (AG), a nitric oxide (NO) synthase inhibitor, precluded the failure of neutrophil migration and protected the animals from death. However, cytokine-induced NO synthase (iNOS)-deficient (iNOS ؊/؊ ) mice subjected to L-CLP did not present neutrophil migration failure, but 100% lethality occurred. iNOS ؊/؊ mice subjected to sublethal sepsis induced by cecal ligation and puncture (SL-CLP) also suffered high mortality despite the occurrence of neutrophil migration. This apparent paradox could be explained by the lack of microbicidal activity in neutrophils of iNOS ؊/؊ mice present at the infection site due to their inability to produce NO. Notably, SL-and L-CLP iNOS ؊/؊ mice showed high bacterial numbers in exudates. The inhibition of neutrophil migration by NO is due to inhibition of a neutrophil/endothelium adhesion mechanism, since a reduction in leukocyte rolling, adhesion, and emigration was observed in L-CLP wild-type mice. These responses were prevented by AG treatment and were not observed in the iNOS ؊/؊ L-CLP group. There was no significant change in L-selectin expression in neutrophils from L-CLP mice. Thus, it seems that the decrease in leukocyte rolling is due to a defect in the expression of adhesion molecules on endothelial surfaces mediated by iNOS-derived NO. In conclusion, the results indicate that despite the importance of NO in neutrophil microbicidal activity, its generation in severe sepsis reduces neutrophil migration by inhibiting leukocyte rolling and their firm adhesion to the endothelium, in effect impairing the migration of leukocytes and consequently their fundamental role in host cell defense mechanisms.

a b s t r a c tMinimally processed leafy vegetables are ready-to-eat (RTE) products very attractive to consumers looking for healthy and convenient meals. However, the microbiological safety of these foods is of special concern due to the absence of lethal treatments during processing. In the present study, indicator microorganisms, Listeria spp. and Salmonella spp. were determined for 162 samples of minimally processed leafy vegetables commercialized in Brazil. Psychrotrophic aerobic bacterial populations >5 log CFU/g were found in 96.7% of the samples, while total and thermotolerant coliforms were detected respectively in 132 (81.5%) and 107 (66%) of vegetables analyzed. Escherichia coli was present in 86 (53.1%) samples analyzed and Listeria spp. and Salmonella spp. were detected respectively in 6 (3.7%) and 2 (1.2%) samples. These results indicate the need of implementing quality programs in the production chain of RTE vegetables to improve shelf life and microbiological safety.

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Objective: To assess the availability of food in relation to their degree of industrial processing and the types of food stores in the perimeters of elementary schools.Method: This is a cross-sectional study. 82 food stores located within a 500 m radius buffer of three public schools located in three distinct regions with different socioeconomic levels in the municipality of Santos, state of São Paulo, Brazil, were assessed. All streets within a 500-meter radius of the schools were covered, geographic coordinates were recorded and information about the stores and food items available were collected by direct observation and interview with store managers. Available food items were classified in relation to their degree of industrial processing as ultra-processed foods and minimally processed foods. Kernel's density maps were used to assess the degree of agglomeration of stores near the schools. Results:The stores that offered mostly ultra-processed foods were significantly closer to schools than those who offered mostly minimally processed foods. There was a significant difference between the availability of processed food in different types of stores and between the three regions assessed. Conclusions:The data found by this work evidences that children who attend the three public schools assessed are exposed to an environment that encourages the consumption of ultra-processed foods through easier access of these products in the studied stores.J Pediatr (Rio J). 2012;88(4):328-34: Nutritional environment, child, processed foods. ResumoObjetivo: Avaliar a disponibilidade de alimentos comercializados em relação ao seu grau de processamento industrial e os tipos de comércios existentes nos perímetros de escolas de ensino fundamental.Métodos: O estudo teve delineamento transversal, e foram avaliados 82 comércios localizados a um raio de 500 metros de três escolas públicas situadas em regiões distintas do município de Santos, que apresentam diferentes níveis socioeconômicos. Foram percorridas todas as ruas existentes nos perímetros das escolas, considerando-se um raio de 500 metros para delimitação da área, tendo sido registradas as coordenadas geográficas e coletadas informações sobre os pontos de venda e sobre os alimentos comercializados, por meio de observação e entrevista com os responsáveis pelo estabelecimento. Os alimentos encontrados foram classificados, em relação ao seu grau de processamento industrial, em: alimentos ultraprocessados e alimentos minimamente processados. Para a avaliação do grau de aglomeração dos estabelecimentos nos perímetros das escolas, foram utilizados mapas de densidade de Kernel.Resultados: Os pontos de vendas que ofertavam, em sua maioria, alimentos ultraprocessados estavam significativamente mais próximos das escolas do que aqueles que ofertavam maioria de alimentos com menor grau de processamento. Observou-se diferença estatisticamente significativa entre a oferta desses alimentos nas diferentes categorias de comércios e entre as três regiões avaliadas. Conclusões:Os dados...

Infection of humans and animals caused by Salmonella is a major public health problem worldwide. Among the more than 2500 serovars, S. Infantis has been one of the 15 most isolated serovars in the world. Despite its clinical importance, little is known about the molecular characteristics of S. Infantis strains from Brazil. The aims of this study were to type S. Infantis isolates of this country and to assess their pathogenic potential. The molecular epidemiology of 35 S. Infantis strains, isolated from human sources (25) and food items (10) between 1984 and 2009 in São Paulo State, Brazil, were investigated using ERIC-PCR, PFGE and MLST. Furthermore, the presence of some virulence markers from Salmonella pathogenicity islands (SPIs) SPI-1 and SPI-2 and from the virulence plasmid was assessed by PCR. Using ERIC-PCR, 34 S. Infantis strains exhibited a high genetic similarity (≥ 93.7%) and using PFGE, 32 strains exhibited a similarity ≥ 80.6%. Additionally, MLST showed a high clonal similarity among strains that all presented the same ST32. Thirty-two isolates under investigation contained the virulence markers invA, sopB, sopD, sipA, sipD, ssaR, sifA, flgK, fljB and flgL. In conclusion, the S. Infantis strains studied were genetically similar, suggesting that a prevalent subtype has been causing disease and food contamination during a 25year period in São Paulo State, an important metropolitan region in Brazil. Furthermore, the contamination between strains from food items and sick humans indicates that better control measures for S. Infantis may be needed in this country.

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Aims Hypertension is associated with increased levels of circulating cytokines and recent studies have shown that innate immunity contributes to hypertension. The mechanisms which hypertension stimulates immune response remain unclear, but may involve formation of neoantigens that activate the immune system. Toll like receptor 4 (TLR4) is an innate immune receptor that binds a wide spectrum of exogenous (lipopolysaccharide) and endogenous ligands. TLR4 signaling leads to activation of nuclear factor kappa B (NFκB) and transcription of genes involved in inflammatory response. We previously demonstrated that TLR4 blockade reduces blood pressure and the augmented vascular contractility in spontaneously hypertensive rats (SHR). Here we hypothesized that inhibition of TLR4 ameliorates the vascular inflammatory process by a NFκB signaling pathway. Main methods SHR and Wistar rats were treated with anti-TLR4 antibody (1µg/day) or unspecific IgG for 15 days (i.p.). Key findings Anti-TLR4 treatment decreased production of reactive oxygen species and expression of IL-6 cytokine in mesenteric resistance arteries from SHR, when compared with IgG-treated SHR. Anti-TLR4 treatment also abolished the increased vascular reactivity to noradrenaline observed in IgG-treated SHR, as described before, and inhibition of NFκB decreased noradrenaline responses only in IgG-treated SHR. Mesenteric arteries from SHR treated with anti-TLR4 displayed decreased expression of MyD88, but not TRIF, key molecules in TLR4 signaling. Phosphorylation of p38 and NF-κB p65 were decreased in arteries from anti-TLR4-treated SHR versus IgG-treated SHR. Significance Together, these results suggest that TLR4 is a key player in hypertension and vascular inflammatory process by a NFκB signaling pathway.