Protein disulfide isomerase-mediated transcriptional upregulation of Nox1 contributes to vascular dysfunction in hypertension.

Nox1 signaling is a causal key element in arterial hypertension. Recently, we identified protein disulfide isomerase A1 (PDI) as a novel regulatory protein that regulates Nox1 signaling in VSMCs. Spontaneously hypertensive rats (SHR) have increased levels of PDI in mesenteric resistance arteries compared with Wistar controls; however, its consequences remain unclear. Herein, we investigated the role of PDI in mediating Nox1 transcriptional upregulation and its effects on vascular dysfunction in hypertension. We demonstrate that PDI contributes to the development of hypertension via enhanced transcriptional upregulation of Nox1 in vascular smooth muscle cells (VSMCs). We show for the first time that PDI sulfenylation by hydrogen peroxide contributes to EGFR activation in hypertension via increased shedding of epidermal growth factor-like ligands. PDI also increases intracellular calcium levels, and contractile responses induced by ANG II. PDI silencing or pharmacological inhibition in VSMCs significantly decreases EGFR activation and Nox1 transcription. Overexpression of PDI in VSMCs enhances ANG II-induced EGFR activation and ATF1 translocation to the nucleus. Mechanistically, PDI increases ATF1-induced Nox1 transcription and enhances the contractile responses to ANG II. Herein we show that ATF1 binding to Nox1 transcription putative regulatory regions is augmented by PDI. Altogether, we provide evidence that HB-EGF in SHR resistance vessels promotes the nuclear translocation of ATF1, under the control of PDI, and thereby induces Nox1 gene expression and increases vascular reactivity. Thus, PDI acts as a thiol redox-dependent enhancer of vascular dysfunction in hypertension and could represent a novel therapeutic target for the treatment of this disease.

Plastic debris forms: Rock analogues emerging from marine pollution.

Continuous input of plastic litter in ocean and coastal environments achieved alarming levels that are exposing new settings in natural systems. While novel plastic debris pollution, with rock-like appearance, has been reported worldwide, fundamentally geological analyses are still lacking. We surveyed the first occurrence of multiple associated plastic debris on a single outcrop located in a remote site (Trindade Island, SE Atlantic Ocean). Even though all plastic debris forms consisted of polypropylene and polyethylene, through a sedimentary approach (cross section, macro, and micro analyses) distinct types were identified. We detected plastiglomerates, geogenic analogous to conglomerates, divided into in situ and clastic types, and formed over beach sediment. We identified plastistones as a new type with homogeneous composition (lacking incorporated materials), geogenic-looking igneous rocks, divided into in situ and clastic types, and formed over rock surfaces. We linked pyroplastics, geogenic analogous to clasts, to clastic plastiglomerates/plastistones, therefore representing clastic types of plastic debris forms. This association was correlated in a depositional system model, which suggests that plastic debris forms are rock synthetic equivalents in which humans act as depositional and post-depositional agents.

Oligocat: Oligoesters as Pseudo-Homogenous Catalysts for Biodiesel Synthesis.

Biodiesel production from first-generation feedstock has shown a strong correlation with the increase in deforestation and the necessity of larger areas for land farming. Recent estimation from the European Federation for Transport and Environment evidenced that since the 2000s decade, an area equal to the Netherlands was deforested to supply global biodiesel demand, mainly originating from first-generation feedstock. Nevertheless, biodiesel is renewable, and it can be a greener source of energy than petroleum. A promising approach to make biodiesel independent from large areas of farming is to shift as much as possible the biodiesel production chain to second and third generations of feedstock. The second generation presents three main advantages, where it does not compete with the food industry, its commercial value is negligible, or none, and its usage as feedstock for biodiesel production reduces the overall waste disposal. In this manuscript, we present an oligomeric catalyst designed to be multi-functional for second-generation feedstock transesterification reactions, mainly focusing our efforts to optimize the conversion of tallow fat and sauteing oil to FAME and FAEE, applying our innovative catalyst. Named as Oligocat, our catalyst acts as a Brønsted-Lowry acid catalyst, providing protons to the reaction medium, and at the same time, with the course of the reaction, it sequesters glycerol molecules from the medium and changes its physical phase during the transesterification reaction. With this set of properties, Oligocat presents a pseudo-homogenous behavior, reducing the purification and separation steps of the biodiesel process production. Reaction conditions were optimized applying a 42 factorial planning. The output parameter evaluated was the conversion rate of triacylglycerol to mono alkyl esters, measured through gel permeation chromatography (GPC). After the optimization studies, a conversion yield of 96.7 (±1.9) wt% was achieved, which allows classifying the obtained mono alkyl esters as biodiesel by ASTM D6751 or EN 14214:2003. After applying the catalyst in three reaction cycles, Oligocat still presented a conversion rate above 96.5 wt% and as well an excellent recovery rate.

Dibenzoylmethane derivative inhibits melanoma cancer in vitro and in vivo through induction of intrinsic and extrinsic apoptotic pathways.

Malignant melanoma has a low incidence, but is the most lethal type of skin cancer. Studies have shown that dibenzoylmethanes (DBMs) have interesting biological activities, including antineoplastic properties. These findings led us to investigate whether news DBM derivatives exert antitumor effects against skin cancers. In a previous study, we found that 1,3-diphenyl-2-benzyl-1,3-propanedione (DPBP) has high in vitro antineoplastic activity against murine B16F10 melanoma cells, with an IC50 of 6.25 µg/mL. In the current study, we used transdermal and topical formulations of DPBP to evaluate its activity and molecular mechanism of action in a murine model of melanoma. The compound induces tumor cell death with high selectivity (selectivity index of 41.94) by triggering apoptosis through intrinsic and extrinsic pathways. DPBP treatment reduced tumor volume as well as serum VEGF-A and uric acid levels. Hepatomegaly and nephrotoxicity were not observed at the tested doses. Histopathological analysis of sentinel lymph nodes revealed no evidence of metastases. According to the observed data, the DPBP compound was effective for the topical treatment of melanoma cancer, suggesting that it acts as a chemotherapeutic or chemopreventive agent.

Respiratory mechanics during methacholine bolus and continuous infusion protocols in asthma model.

Balb/c mice respiratory mechanics was studied in two intravenous methacholine (MCh) protocols: bolus and continuous infusion. The Constant Phase Model (CPM) was used in this study. The harmonic distortion index (kd) was used to assess the respiratory system nonlinearity. The analysis of variance showed difference between groups (OVA vs control) and among doses for both protocols. Bolus protocol posttest: there was a difference between OVA and control at 0.3 and 1 mg/kg doses (p<0.0001 and p<0.001) for Rn. Infusion: there was a difference between OVA and control at 192 µg.kg-1.min-1 dose for Rn, G and H, (p<0.01; p<0.001; p<0.001). An increment was found in kd values near to the observed peak values in bolus protocol. The bolus protocol could better differentiate inflamed and non-inflamed airway resistance, whereas the differences between OVA and control in continuous infusion protocol were associated to airway- and, mainly, parenchyma-related parameters. Moreover, the bolus protocol presented a higher nonlinear degree compared to the infusion protocol.

Incidência de aflatoxinas B1, B2, G1 e G2 em amendoins / Incidence of aflatoxins B1, B2, G1 and G2 in peanuts

Micotoxinas são substâncias tóxicas produzidas por fungos e encontradas nos alimentos. As micotoxinas mais tóxicas são as aflatoxinas, produzidas, principalmente por Aspergillus flavus. Estudos realizados no país demonstraram alta incidência dessas micotoxinas em produtos de amendoim, que representa risco à saúde da população. O objetivo do estudo foi avaliar a incidência de aflatoxinas B1, B2, G1 e G2 em amostras de amendoins comercializados na região Nordeste do Estado de São Paulo nos períodos de 1994-2001 e 2016-2017. O método utilizado para analisar as amostras no primeiro período foi extração líquido-líquido e cromatografia em camada delgada e no segundo foi utilizando colunas de imunoafinidade, cromatografia líquida com derivatização pós- coluna e detector por fluorescência. No levantamento de 1994-2001 das 82 amostras, 39% tiveram contaminação de aflatoxinas variando de 11 a 1556 µg/kg com 37% das amostras contendo níveis maiores que 20 µg/kg, enquanto na pesquisa de 2016-17, das 56 amostras, 38% apresentaram contaminação destas toxinas variando de 0,09 a 60,40 µg/kg com 13% das amostras contendo níveis maiores que 20 µg/kg. Os resultados dos dois períodos estudados indicam que houve uma diminuição na incidência e nível das aflatoxinas estudadas, embora esta contaminação em amendoim permaneça um problema de saúde pública. (AU)

Mycotoxins are toxic compounds produced by fungi found in food. The most toxic mycotoxins are the aflatoxins produced mainly by Aspergillus flavus . Studies carried out in Brazil showed a high incidence of these mycotoxins in peanut products, a fact that represents public health problems. The aim of the study was to evaluate aflatoxins B1, B2, G1, and G2 in samples of peanuts sold in cities of the Northeast of the State of São Paulo in the period from 1994 to 2001 and from 2016 to 2017. The samples of the first period were analyzed using liquid-liquid extraction and thin-layer chromatography and the second using immunoaffinity columns, post-column derivative liquid chromatography and fluorescence detector. In the 1994-2001 survey, among 82 samples, 39% presented aflatoxins contamination ranging from 11 to 1556 µg/kg with 37% with levels greater than 20 µg/kg whereas, in the 2016-17 survey, 38% of the 56 samples presented contamination of aflatoxins ranging from 0.09 to 60.40 µg/kg and 7 samples 13% containing aflatoxins levels higher than 20 µg/kg. The results indicated there was a decrease in the incidence and level of aflatoxins, but the contamination of aflatoxins in peanuts remains a public health problem. (AU)

Incidência de aflatoxinas B1, B2, G1 e G2 em amendoins / Incidence of aflatoxins B1, B2, G1 and G2 in peanuts

Micotoxinas são substâncias tóxicas produzidas por fungos e encontradas nos alimentos. As micotoxinas mais tóxicas são as aflatoxinas, produzidas, principalmente por Aspergillus flavus. Estudos realizados no país demonstraram alta incidência dessas micotoxinas em produtos de amendoim, que representa risco à saúde da população. O objetivo do estudo foi avaliar a incidência de aflatoxinas B1, B2, G1 e G2 em amostras de amendoins comercializados na região Nordeste do Estado de São Paulo nos períodos de 1994-2001 e 2016-2017. O método utilizado para analisar as amostras no primeiro período foi extração líquido-líquido e cromatografia em camada delgada e no segundo foi utilizando colunas de imunoafinidade, cromatografia líquida com derivatização pós-coluna e detector por fluorescência. No levantamento de 1994-2001 das 82 amostras, 39% tiveram contaminação de aflatoxinas variando de 11 a 1556 μg/kg com 37% das amostras contendo níveis maiores que 20 μg/kg, enquanto na pesquisa de 2016-17, das 56 amostras, 38% apresentaram contaminação destas toxinas variando de 0,09 a 60,40 μg/kg com 13% das amostras contendo níveis maiores que 20 μg/kg. Os resultados dos dois períodos estudados indicam que houve uma diminuição na incidência e nível das aflatoxinas estudadas, embora esta contaminação em amendoim permaneça um problema de saúde pública.

Mycotoxins are toxic compounds produced by fungi found in food. The most toxic mycotoxins are the aflatoxins produced mainly by Aspergillus flavus. Studies carried out in Brazil showed a high incidence of these mycotoxins in peanut products, a fact that represents public health problems. The aim of the study was to evaluate aflatoxins B1, B2, G1, and G2 in samples of peanuts sold in cities of the Northeast of the State of São Paulo in the period from 1994 to 2001 and from 2016 to 2017. The samples of the first period were analyzed using liquid-liquid extraction and thin-layer chromatography and the second using immunoaffinity columns, post-column derivative liquid chromatography and fluorescence detector. In the 1994-2001 survey, among 82 samples, 39% presented aflatoxins contamination ranging from 11 to 1556 μg/kg with 37% with levels greater than 20 μg/kg whereas, in the 2016-17 survey, 38% of the 56 samples presented contamination of aflatoxins ranging from 0.09 to 60.40 μg/kg and 7 samples 13% containing aflatoxins levels higher than 20 μg/kg. The results indicated there was a decrease in the incidence and level of aflatoxins, but the contamination of aflatoxins in peanuts remains a public health problem.

Frutanos tipo inulina associados à dieta de cafeteria: efeito no perfil cardiometabólico de ratos Wistar / Inulin-type fructan associated with cafeteria diet: effect on the cardiometabolic profile of Wistar rats

A dieta de cafeteria foi desenvolvida a fim de mimetizar a dieta ocidentalizada, uma vez que esta associa-se a desordens no perfil cardiovascular, como dislipidemias, hiperglicemia, acúmulo de gordura corporal, entre outros. Os frutanos tipo inulina (FTI) são fibras solúveis categorizados como prebióticos. O presente estudo objetivou avaliar os efeitos da dieta de cafeteria associadas aos FTI sobre o perfil cardiometabólico em ratos Wistar. Para tanto, utilizou-se 30 animais. Os FTI purificados, bem como, provenientes da matriz alimentar (yacon em pó), foram adicionados a seus respectivos grupos experimentais na dose de 6%, durante 30 dias. As variáveis analisadas foram: composição centesimal e conteúdo de FTI, ganho de peso (GP), peso relativo do ceco (PRC), peso relativo do fígado (PRF), consumo alimentar, glicemia, triglicerídeos, colesterol total, HDL-c, LDL-c, tecido adiposo subcutâneo e visceral (epididimal, retroperitoneal e mesentérica). Todas as análises seguiram os protocolos padronizados. A análise estatística foi realizada no software Sigma Stat 4.0 e teste de normalidade de Shapiro-Wilk, testes descritivos, ANOVA ou teste de Kruskal-Wallis seguidos dos testes de comparação de médias de Duncan ou Dunn's. O nível de significância adotado foi de p<0,05. A variável PRC foi estatisticamente maior nos grupos submetidos aos FTI. O grupo que recebeu dieta de cafeteria apresentou valores superiores no GP, VLDL, triglicerídeos, tecido adiposo subcutâneo e epididimal. Não houve diferença estatística nos parâmetros PRF, colesterol total, LDL-c, HDL-c e glicemia. Portanto, através deste trabalho, verificou-se efeitos sistêmicos benéficos dos FTI em parâmetros como: PRC, GP, VLDL, triglicerídeos, tecido adiposo(AU)

The cafeteria diet was developed in order to mimic the western diet, since it is associated with disorders in the cardiovascular profile, such as dyslipidemia, hyperglycemia, accumulation of body fat, among others. Inulin-type fructan (ITF) are soluble fibers categorized as prebiotics. The present study aimed to evaluate the effects of ITF associated with cafeteria diet on the cardiometabolic profile in Wistar rats. For this, 30 animals were used. The purified ITFs, as well as from the food matrix (yacon powder), were added to their respective experimental groups at a dose of 6% for 30 days. The analyzed variables were: centesimal composition and ITF content, weight gain (WG), relative weight of cecum (RWC), relative liver weight (RLW), dietary intake, glycemia, triglycerides, total cholesterol, HDL-c, LDL -c, subcutaneous and visceral adipose tissue (epididimal, retroperitoneal and mesenteric). All analyzes followed the standardized protocols. Statistical analysis was performed using the Sigma Stat 4.0 software and a Shapiro-Wilk normality test, descriptive tests, ANOVA or Kruskal-Wallis test followed by the Duncan or Dunn's averages comparison tests were performed. The level of significance was set at p <0.05. The RWC variable was statistically higher in the groups submitted to FTI. The group that received a cafeteria diet presented higher values in WG, VLDL, triglycerides, subcutaneous and epididimal adipose tissue. There was no statistical difference in the parameters RLW, total cholesterol, LDL-c, HDL-c and glycemia. Therefore, through this work, beneficial systemic effects of ITF were observed in parameters such as: RWC, WG, VLDL, triglycerides and adipose tissue(AU)

The role of inter-regional flows in the spread of epidemics in a city of regional influence with a tropical climate. / El papel de los flujos interregionales en la diseminación de epidemias de dengue en una ciudad de clima tropical.

The aim of this research was to investigate the origin of imported cases of dengue in the city of Araraquara, Brazil and to describe the disease's main epidemiological characteristics. The study encompassed all confirmed cases of dengue recorded in the Information System for Notifiable Diseases (SINAN) [Sistema de Informação de Agravos de Notificação] from 1998 to 2013. Cases whose origin of infection was likely located outside Araraquara were considered imported. The epidemiological study entailed a descriptive analysis of the data, regarding the distribution of cases by sex, age, and classification of imported and autochthonous cases. A geographic information system was used to map flows and estimate distances. There were 6,913 confirmed cases, 419 of which were imported. In most cases, the origin of infection was located in the state of São Paulo as well as other Brazilian regions. The results indicate the relevance of imported cases and differences in the epidemiological profile with respect to age and sex. Conclusions indicate the need to increase epidemiological and environmental health surveillance at ports, airports, truck stops, and bus and train terminals.

El objetivo de este trabajo fue investigar el origen de los casos importados de dengue en la ciudad de Araraquara, Brasil y describir las principales características epidemiológicas. El estudio abarcó todos los casos confirmados de dengue registrados en el Sistema de Información de Enfermedades de Notificación (SINAN) [Sistema de Informação de Agravos de Notificação] de 1998-2013. Se consideraron como casos importados aquellos cuyo lugar de origen de infección se ubicara fuera de Araraquara. Se realizó un análisis descriptivo de la distribución de los casos por género, edad y clasificación de casos importados y autóctonos. Se utilizó un sistema de información geográfica para mapear los flujos y estimar las distancias de los puntos de contagio. Se incluyeron 6.913 casos confirmados, de los cuales 419 fueron importados. En la mayoría de estos casos, el origen de infección se ubicó en el estado de San Pablo, además de otras regiones brasileñas. Los resultados indican la relevancia de los casos importados y diferencias en el perfil epidemiológico por edad y sexo. Las conclusiones indican la necesidad de aumentar la vigilancia epidemiológica y de salud ambiental en los puertos, aeropuertos, paradas de camiones y terminales de buses y trenes.

Detrimental Effects of Testosterone Addition to Estrogen Therapy Involve Cytochrome P-450-Induced 20-HETE Synthesis in Aorta of Ovariectomized Spontaneously Hypertensive Rat (SHR), a Model of Postmenopausal Hypertension.

Postmenopausal period has been associated to different symptoms such as hot flashes, vulvovaginal atrophy, hypoactive sexual desire disorder (HSDD) and others. Clinical studies have described postmenopausal women presenting HSDD can benefit from the association of testosterone to conventional hormonal therapy. Testosterone has been linked to development of cardiovascular diseases including hypertension and it also increases cytochrome P-450-induced 20-HETE synthesis which in turn results in vascular dysfunction. However, the effect of testosterone plus estrogen in the cardiovascular system is still very poorly studied. The aim of the present study is to evaluate the role of cytochrome P-450 pathway in a postmenopausal hypertensive female treated with testosterone plus estrogen. For that, hypertensive ovariectomized rats (OVX-SHR) were used as a model of postmenopausal hypertension and four groups were created: SHAM-operated (SHAM), ovariectomized SHR (OVX), OVX treated for 15 days with conjugated equine estrogens [(CEE) 9.6 µg/Kg/day/po] or CEE associated to testosterone [(CEE+T) 2.85 mg/kg/weekly/im]. Phenylephrine-induced contraction and generation of reactive oxygen species (ROS) were markedly increased in aortic rings from OVX-SHR compared to SHAM rats which were restored by CEE treatment. On the other hand, CEE+T abolished vascular effects by CEE and augmented both systolic and diastolic blood pressure of SHR. Treatment of aortic rings with the CYP/20-HETE synthesis inhibitor HET0016 (1 µM) reduced phenylephrine hyperreactivity and the augmented ROS generation in the CEE+T group. These results are paralleled by the increased CYP4F3 protein expression and activity in aortas of CEE+T. In conclusion, we showed that association of testosterone to estrogen therapy produces detrimental effects in cardiovascular system of ovariectomized hypertensive females via CYP4F3/20-HETE pathway. Therefore, our findings support the standpoint that the CYP/20-HETE pathway is an important therapeutic target for the prevention of cardiovascular disease in menopausal women in the presence of high levels of testosterone.

El papel de los flujos interregionales en la diseminación de epidemias de dengue en una ciudad de clima tropical / The role of inter-regional flows in the spread of epidemics in a city of regional influence with a tropical climate

RESUMEN El objetivo de este trabajo fue investigar el origen de los casos importados de dengue en la ciudad de Araraquara, Brasil y describir las principales características epidemiológicas. El estudio abarcó todos los casos confirmados de dengue registrados en el Sistema de Información de Enfermedades de Notificación (SINAN) [Sistema de Informação de Agravos de Notificação] de 1998-2013. Se consideraron como casos importados aquellos cuyo lugar de origen de infección se ubicara fuera de Araraquara. Se realizó un análisis descriptivo de la distribución de los casos por género, edad y clasificación de casos importados y autóctonos. Se utilizó un sistema de información geográfica para mapear los flujos y estimar las distancias de los puntos de contagio. Se incluyeron 6.913 casos confirmados, de los cuales 419 fueron importados. En la mayoría de estos casos, el origen de infección se ubicó en el estado de San Pablo, además de otras regiones brasileñas. Los resultados indican la relevancia de los casos importados y diferencias en el perfil epidemiológico por edad y sexo. Las conclusiones indican la necesidad de aumentar la vigilancia epidemiológica y de salud ambiental en los puertos, aeropuertos, paradas de camiones y terminales de buses y trenes.

ABSTRACT The aim of this research was to investigate the origin of imported cases of dengue in the city of Araraquara, Brazil and to describe the disease's main epidemiological characteristics. The study encompassed all confirmed cases of dengue recorded in the Information System for Notifiable Diseases (SINAN) [Sistema de Informação de Agravos de Notificação] from 1998 to 2013. Cases whose origin of infection was likely located outside Araraquara were considered imported. The epidemiological study entailed a descriptive analysis of the data, regarding the distribution of cases by sex, age, and classification of imported and autochthonous cases. A geographic information system was used to map flows and estimate distances. There were 6,913 confirmed cases, 419 of which were imported. In most cases, the origin of infection was located in the state of São Paulo as well as other Brazilian regions. The results indicate the relevance of imported cases and differences in the epidemiological profile with respect to age and sex. Conclusions indicate the need to increase epidemiological and environmental health surveillance at ports, airports, truck stops, and bus and train terminals.

Association of neighbourhood food availability with the consumption of processed and ultra-processed food products by children in a city of Brazil: a multilevel analysis.

OBJECTIVE: To investigate the association between neighbourhood food availability and the consumption of ready-to-consume products (RCP), either processed or ultra-processed, and unprocessed/minimally processed foods (UF-MPF) by children. DESIGN: Cross-sectional. 24 h Dietary recalls were collected from children from January 2010 to June 2011. Neighbourhood food availability data were collected from 672 food stores located within 500 m of participants' homes, using an adapted and validated instrument. Neighbourhood-level socio-economic status (SES) was obtained by calculating the mean years of household head's education level in each census tract covered by 500 m buffers. Foods that were consumed by children and/or available in the food stores were classified based on their degree of industrial processing. Multilevel random-effect models examined the association between neighbourhood food availability and children's diets. SETTING: Santos, Brazil. SUBJECTS: Children (n 513) under 10 years old (292 aged <6 years, 221 aged ≥6 years). RESULTS: The availability of RCP in food stores was associated with increased RCP consumption (P<0·001) and decreased UF-MPF consumption (P<0·001). The consumption of UF-MPF was positively associated with neighbourhood-level SES (P<0·01), but not with the availability of UF-MPF in the neighbourhood. CONCLUSIONS: Results suggest that food policies and interventions that aim to reduce RCP consumption in Santos and similar settings should focus on reducing the availability in food stores. The results also suggest that interventions should not only increase the availability of UF-MPF in lower-SES neighbourhoods, but should strive to make UF-MPF accessible within these environments.

How Can Urban Policies Improve Air Quality and Help Mitigate Global Climate Change: a Systematic Mapping Review.

Tackling climate change at the global level is central to a growing field of scientific research on topics such as environmental health, disease burden, and its resulting economic impacts. At the local level, cities constitute an important hub of atmospheric pollution due to the large amount of pollutants that they emit. As the world population shifts to urban centers, cities will increasingly concentrate more exposed populations. Yet, there is still significant progress to be made in understanding the contribution of urban pollutants other than CO2, such as vehicle emissions, to global climate change. It is therefore particularly important to study how local governments are managing urban air pollution. This paper presents an overview of local air pollution control policies and programs that aim to reduce air pollution levels in megacities. It also presents evidence measuring their efficacy. The paper argues that local air pollution policies are not only beneficial for cities but are also important for mitigating and adapting to global climate change. The results systematize several policy approaches used around the world and suggest the need for more in-depth cross-city studies with the potential to highlight best practices both locally and globally. Finally, it calls for the inclusion of a more human rights-based approach as a mean of guaranteeing of clean air for all and reducing factors that exacerbate climate change.

Association of testosterone with estrogen abolishes the beneficial effects of estrogen treatment by increasing ROS generation in aorta endothelial cells.

Testosterone has been added to hormone replacement therapy to treat sexual dysfunction in postmenopausal women. Whereas estrogen has been associated with vascular protection, the vascular effects of testosterone are contradictory and the effects of its association with estrogen are largely unknown. In this study we determined the effects of testosterone associated with conjugated equine estrogen (CEE) on vascular function using a model of hypertensive postmenopausal female: ovariectomized spontaneously hypertensive rats. Female spontaneously hypertensive rats were divided into sham-operated, ovariectomized (OVX), and OVX treated for 15 days with either CEE alone (OVX+CEE) or associated with testosterone (OVX+CEE+T). Angiotensin II (ANG II)-induced contraction was markedly increased in aortic rings from OVX compared with sham-operated rats. CEE treatment restored ANG-II responses, a beneficial effect abrogated with CEE+T. CEE treatment also increased endothelium-dependent relaxation, which was impaired in OVX rats. This effect was lost by CEE+T. Treatment of aortas with losartan (ANG-II type-1 receptor antagonist) or apocynin (NADPH-oxidase inhibitor) restored the endothelium-dependent relaxation in OVX and CEE+T, establishing an interplay between ANG-II and endothelial dysfunction in OVX and CEE+T. The benefits by CEE were associated with downregulation of NADPH-oxidase subunits mRNA expression and decreased reactive oxygen species generation. The association of testosterone with CEE impairs the benefits of estrogen on OVX-associated endothelial dysfunction and reactive oxygen species generation in rat aorta by a mechanism that involves phosphorylation of the cytosolic NADPH-oxidase subunit p47(phox).

Testosterone induces leucocyte migration by NADPH oxidase-driven ROS- and COX2-dependent mechanisms.

The mechanisms whereby testosterone increases cardiovascular risk are not clarified. However, oxidative stress and inflammation seem to be determinants. Herein, we sought to determine whether exogenous testosterone, at physiological levels, induces leucocyte migration, a central feature in immune and inflammatory responses and the mediating mechanisms. We hypothesized that testosterone induces leucocyte migration via NADPH oxidase (NADPHox)-driven reactive oxygen species (ROS) and cyclooxygenase (COX)-dependent mechanisms. Sixteen-week-old Wistar rats received an intraperitoneal injection (5 ml) of either testosterone (10(-7) mol/l) or saline. Rats were pre-treated with 5 ml of sodium salicylate (SS, non-selective COX inhibitor, 1.25 × 10(-3) mol/l, 1 h prior to testosterone or saline), flutamide (androgen receptor antagonist, 10(-5) mol/l), apocynin (NADPHox inhibitor, 3 × 10(-4) mol/l), N-[2-Cyclohexyloxy-4-nitrophenyl]methanesulfonamide (NS398, COX2 inhibitor, 10(-4) mol/l) or saline, 4 h before testosterone or saline administration. Leucocyte migration was assessed 24 h after testosterone administration by intravital microscopy of the mesenteric bed. Serum levels of testosterone were measured by radioimmunoassay. NADPHox activity was assessed in membrane fractions of the mesenteric bed by dihydroethidium (DHE) fluorescence and in isolated vascular smooth muscle cells (VSMC) by HPLC. NADPHox subunits and VCAM (vascular cell adhesion molecule) expression were determined by immunoblotting. Testosterone administration did not change serum levels of endogenous testosterone, but increased venular leucocyte migration to the adventia, NADPHox activity and expression (P < 0.05). These effects were blocked by flutamide. SS inhibited testosterone-induced leucocyte migration (P<0.05). Apocynin and NS398 abolished testosterone-induced leucocyte migration and NADPHox activity (P<0.05). Testosterone induces leucocyte migration via NADPHox- and COX2-dependent mechanisms and may contribute to inflammatory processes and oxidative stress in the vasculature potentially increasing cardiovascular risk.

CagA phosphorylation EPIYA-C motifs and the vacA i genotype in Helicobacter pylori strains of asymptomatic children from a high-risk gastric cancer area in northeastern Brazil.

Helicobacter pylori infection is one of the most common infections worldwide and is associated with gastric diseases. Virulence factors such as VacA and CagA have been shown to increase the risk of these diseases. Studies have suggested a causal role of CagA EPIYA-C in gastric carcinogenesis and this factor has been shown to be geographically diverse. We investigated the number of CagA EPIYA motifs and the vacA i genotypes in H. pylori strains from asymptomatic children. We included samples from 40 infected children (18 females and 22 males), extracted DNA directly from the gastric mucus/juice (obtained using the string procedure) and analysed the DNA using polymerase chain reaction and DNA sequencing. The vacA i1 genotype was present in 30 (75%) samples, the i2 allele was present in nine (22.5%) samples and both alleles were present in one (2.5%) sample. The cagA-positive samples showed distinct patterns in the 3’ variable region of cagA and 18 of the 30 (60%) strains contained 1 EPIYA-C motif, whereas 12 (40%) strains contained two EPIYA-C motifs. We confirmed that the studied population was colonised early by the most virulent H. pylori strains, as demonstrated by the high frequency of the vacA i1 allele and the high number of EPIYA-C motifs. Therefore, asymptomatic children from an urban community in Fortaleza in northeastern Brazil are frequently colonised with the most virulent H. pylori strains.

CagA phosphorylation EPIYA-C motifs and the vacA i genotype in Helicobacter pylori strains of asymptomatic children from a high-risk gastric cancer area in northeastern Brazil

Helicobacter pylori infection is one of the most common infections worldwide and is associated with gastric diseases. Virulence factors such as VacA and CagA have been shown to increase the risk of these diseases. Studies have suggested a causal role of CagA EPIYA-C in gastric carcinogenesis and this factor has been shown to be geographically diverse. We investigated the number of CagA EPIYA motifs and the vacA i genotypes in H. pylori strains from asymptomatic children. We included samples from 40 infected children (18 females and 22 males), extracted DNA directly from the gastric mucus/juice (obtained using the string procedure) and analysed the DNA using polymerase chain reaction and DNA sequencing. The vacA i1 genotype was present in 30 (75%) samples, the i2 allele was present in nine (22.5%) samples and both alleles were present in one (2.5%) sample. The cagA-positive samples showed distinct patterns in the 3’ variable region of cagA and 18 of the 30 (60%) strains contained 1 EPIYA-C motif, whereas 12 (40%) strains contained two EPIYA-C motifs. We confirmed that the studied population was colonised early by the most virulent H. pylori strains, as demonstrated by the high frequency of the vacA i1 allele and the high number of EPIYA-C motifs. Therefore, asymptomatic children from an urban community in Fortaleza in northeastern Brazil are frequently colonised with the most virulent H. pylori strains. .