Resveratrol affects differently rat liver and brain mitochondrial bioenergetics and oxidative stress in vitro: Investigation of the role of gender

Resveratrol (3,5,40-trihydroxy-trans stilbene) is commonly recognized by its antioxidant properties. Despite its beneficial qualities, the toxic effects of this natural compound are still unknown. Since mitochondria are essential to support the energy-dependent regulation of several cell functions, the objective of this study was to evaluate resveratrol effects on rat brain and liver mitochondrial fractions from male and females regarding oxidative stress and bioenergetics. No basal differences were observed between mitochondrial fractions from males and females, except in liver mitochondria, the generation of H2O2 by the respiratory chain is lower for female preparations. Resveratrol inhibited lipid peroxidation in preparations from both genders and organs. Furthermore, brain mitochondria in both gender groups appeared susceptible to resveratrol as seen by a decrease in state 3 respiration and alterations in mitochondrial membrane potential fluctuations during ADP phosphorylation. As opposed, liver mitochondria were less affected by resveratrol. Our data also demonstrates that resveratrol inhibits complex I activity in all mitochondrial preparations. The results suggest that brain mitochondria appear to be more susceptible to resveratrol effects, and gender appears to play a minor role. It remains to be determined if resveratrol effects on brain mitochondria contribute to deterioration of mitochondrial function or instead to mediate hormesis-mediated events.This work is supported by PTDC/AGR-ALI/108326/2008 to M.S.S. from the Portuguese Foundation for Science and Technology, FEDER/ Compete/National Funds. A.C.M., A.M.S. and V.A.S. are recipient of SFRH/BD/33892/2009, SFRH/BD/76086/2011 and SFRH/BPD/ 31549/2006 fellowships, respectively

EVALUACIÓN DE LA CAPACIDAD DE INDUCCIÓN DE ANTIXENOSIS DE DOS COMPUESTOS (CINAMATO DE METILO Y ETILO) PARA CONTROLAR AL PULGÓN VERDE DE LOS CEREALES EN AVENA

La avena es el principal cereal invernal empleado como verdeo en nuestro país, cuya producción y rendimiento está afectada entre otros factores, por la presencia del pulgón verde (Schizaphis graminum). El manejo inadecuado de productos fitosanitarios ha tenido numerosas consecuencias negativas, por lo que es imperante buscar alternativas sustentables, y la integración e implementación de diferentes estrategias de control de insectos plagas tales como el uso de cultivares tolerantes y el empleo de compuestos orgánicos que apliquen los postulados de la Química Verde. Los defensas inducidas son aquellas que se generan cuando la planta detecta que está siendo atacada por patógenos y /o insectos plaga, este mecanismo esta mediado por algunas fitohormonas [1, 2], entre ellas el ácido salicílico (AS), quien tiene un rol esencial en la activación de genes de defensas que codifican para proteínas PR (proteínas asociadas a la patogénesis), y de respuesta hipersensible (RH) [3]. Se definió la antixenosis como la capacidad de las plantas de no compatibilizar con el insecto, evitando que el insecto la utilice para oviposición, alimento o refugio [4]. El Objetivo fue evaluar la capacidad de inducción de antixenosis de dos compuestos orgánicos precursores del AS (R1: cinamato de metilo y R2: cinamato de etilo), sintetizados mediantes procedimientos de bajo impacto ambiental. Se utilizaron 16 cultivares de avenas obtenidas en la CEI de Barrow y dos compuestos orgánicos R1 y R2, cuya preparación se realizó bajo procesos sustentables en la cátedra de Química Orgánica. La evaluación de antixenosis en los 16 cultivares se realizó mediante la prueba de libre selección de hospedero, en condiciones controladas de Tº, y fotoperíodo (22± 1°C; 12:12 L: O). En el estado de segunda hoja expandida (Zadok Z: 1.2) se formó un circulo con los 16 cultivares, en el centro del mismo se colocaron aproximadamente entre 7- 10 hembras ápteras adultas. A las 24 hs de la infestación se hizo el recuento del Nº áfido por cada planta. Se empleó un diseño complemente aleatorizado con 10 repeticiones (10 círculos), la ubicación de cada variedad fue sorteada al azar, hubo tres tratamientos (Testigo, R1 y R2). Se aplicó una dilución de 1x10-5 M en R1 y R2, y con Tween20 y agua en el grupo Testigo, mediante aspersión exógena hasta chorreo, 24 h antes de la infestación con los insectos, luego, se realizó el conteo del Número de insectos por planta. Los datos de los experimentos se analizaron por separado mediante análisis de varianza (ANOVA) y las medias de los distintos cultivares se compararon usando el Test de Tukey. Para un mejor ajuste a la normalidad, los datos fueron transformados con la fórmula Log (X+1). La aplicación del análisis de la varianza demostró la presencia de diferencias altamente significativas solamente para Tratamientos con los dos compuestos orgánicos (tablas 1 y 2). En el tratamiento con R1 se observó que los cultivares Nº 9 y el Nº 13 vieron mejorada significativamente su antixenosis, al condicionar un menor número de insectos por planta en relación al testigo, mientras que los restantes cultivares no modificaron tal condición (figura Nº 1). En tanto, en el tratamiento con R2, los cultivares Nº 1, 3, 4, 6, 9 y 12 mostraron un menor número de insectos por planta en relación al testigo, resultando ser más antixenoticos (figura Nº2). El único cultivar que respondió con ambos tratamientos (R1 y R2) fue el Nº 9. Se sugiere que los cambios observados en el nivel de antixenosis en los materiales estudiados podrían ser atribuidos al tratamiento con los compuestos orgánicos. Los resultados indicarían mejor efectividad en el control de los áfidos del cinamato de etilo (R2), sin embargo se sugieren más estudios para corroborar su acción repelente. La aplicación del análisis de la varianza demostró la presencia de diferencias altamente significativas solamente para Tratamientos con los dos compuestos orgánicos (tablas 1 y 2). En el tratamiento con R1 se observó que los cultivares Nº 9 y el Nº 13 vieron mejorada significativamente su antixenosis, al condicionar un menor número de insectos por planta en relación al testigo, mientras que los restantes cultivares no modificaron tal condición (figura 1). En tanto, en el tratamiento con R2, los cultivares Nº 1, 3, 4, 6, 9 y 12 mostraron un menor número de insectos por planta en relación al testigo, resultando ser más antixenoticos (figura 2). El único cultivar que respondió con ambos tratamientos (R1 y R2) fue el Nº 9. Se sugiere que los cambios observados en el nivel de antixenosis en los materiales estudiados podrían ser atribuidos al tratamiento con los compuestos orgánicos. Los resultados indicarían mejor efectividad en el control de los áfidos del cinamato de etilo (R2), sin embargo se sugieren más estudios para corroborar su acción repelente

Regulation of Amyloid Oligomer Binding to Neurons and Neurotoxicity by the Prion Protein-mGluR5 Complex

The prion protein (PrPC) has been suggested to operate as a scaffold/receptor protein in neurons, participating in both physiological and pathological associated events. PrPC, laminin, and metabotropic glutamate receptor 5 (mGluR5) form a protein complex on the plasma membrane that can trigger signaling pathways involved in neuronal differentiation. PrPC and mGluR5 are co-receptors also for -amyloid oligomers (AOs) and have been shown to modulate toxicity and neuronal death in Alzheimer\u27s disease. In the present work, we addressed the potential crosstalk between these two signaling pathways, laminin-PrPC-mGluR5 or AO-PrPC-mGluR5, as well as their interplay. Herein, we demonstrated that an existing complex containing PrPC-mGluR5 has an important role in AO binding and activity in neurons. A peptide mimicking the binding site of laminin onto PrPC (Ln-1) binds to PrPC and induces intracellular Ca2+ increase in neurons via the complex PrPC-mGluR5. Ln-1 promotes internalization of PrPC and mGluR5 and transiently decreases AO biding to neurons; however, the peptide does not impact AO toxicity. Given that mGluR5 is critical for toxic signaling by AOs and in prion diseases, we tested whether mGlur5 knock-out mice would be susceptible to prion infection. Our results show mild, but significant, effects on disease progression, without affecting survival of mice after infection. These results suggest that PrPC-mGluR5 form a functional response unit by which multiple ligands can trigger signaling. We propose that trafficking of PrPC-mGluR5 may modulate signaling intensity by different PrPC ligands

Verbal and visual stimulation effects on rectus femoris and biceps femoris muscles during isometric and concentric

Abstract Background: Coactivation may be both desirable (injury prevention) or undesirable (strength measurement). In this context, different styles of muscle strength stimulus have being investigated. In this study we evaluated the effects of verbal and visual stimulation on rectus femoris and biceps femoris muscles contraction during isometric and concentric. Methods: We investigated 13 men (age =23.1 ± 3.8 years old; body mass =75.6 ± 9.1 kg; height =1.8 ± 0.07 m). We used the isokinetic dynamometer BIODEX device and an electromyographic (EMG) system. We evaluated the maximum isometric and isokinetic knee extension and flexion at 60°/s. The following conditions were evaluated: without visual nor verbal command (control); verbal command; visual command and; verbal and visual command. In relation to the concentric contraction, the volunteers performed five reciprocal and continuous contractions at 60°/s. With respect to isometric contractions it was made three contractions of five seconds for flexion and extension in a period of one minute. Results: We found that the peak torque during isometric flexion was higher in the subjects in the VVC condition (p > 0.05). In relation to muscle coactivation, the subjects presented higher values at the control condition (p > 0.05). \ud \ud \ud Conclusion\ud We suggest that this type of stimulus is effective for the lower limbs.This study received financial support from Universidade do Vale do Paraíba

Incidence and risk factors for Preeclampsia in a cohort of healthy nulliparous pregnant women: a nested case-control study

The objective of this study is to determine the incidence, socio-demographic and clinical risk factors for preeclampsia and associated maternal and perinatal adverse outcomes. This is a nested case-control derived from the multicentre cohort study Preterm SAMBA, in five different centres in Brazil, with nulliparous healthy pregnant women. Clinical data were prospectively collected, and risk factors were assessed comparatively between PE cases and controls using risk ratio (RR) (95% CI) plus multivariate analysis. Complete data were available for 1,165 participants. The incidence of preeclampsia was 7.5%. Body mass index determined at the first medical visit and diastolic blood pressure over 75 mmHg at 20 weeks of gestation were independently associated with the occurrence of preeclampsia. Women with preeclampsia sustained a higher incidence of adverse maternal outcomes, including C-section (3.5 fold), preterm birth below 34 weeks of gestation (3.9 fold) and hospital stay longer than 5 days (5.8 fold) than controls. They also had worse perinatal outcomes, including lower birthweight (a mean 379 g lower), small for gestational age babies (RR 2.45 [1.52-3.95]), 5-minute Apgar score less than 7 (RR 2.11 [1.03-4.29]), NICU admission (RR 3.34 [1.61-6.9]) and Neonatal Near Miss (3.65 [1.78-7.49]). Weight gain rate per week, obesity and diastolic blood pressure equal to or higher than 75 mmHg at 20 weeks of gestation were shown to be associated with preeclampsia. Preeclampsia also led to a higher number of C-sections and prolonged hospital admission, in addition to worse neonatal outcomes9CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ401636/2013-5Bill and Melinda Gates FoundationGates Foundation [OPP1107597]; CNPqNational Council for Scientific and Technological Development (CNPq) [401636/2013-5

Glucocorticoid: Major Factor for Reduced Immunogenicity of 2009 Influenza A (H1N1) Vaccine in Patients with Juvenile Autoimmune Rheumatic Disease

Objective. To assess the immunogenicity and safety of non-adjuvanted influenza A H1N1/2009 vaccine in patients with juvenile autoimmune rheumatic disease (ARD) and healthy controls, because data are limited to the adult rheumatologic population. Method's. A total of 237 patients with juvenile ARD [juvenile systemic lupus erythematosus (JSLE), juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM), juvenile scleroderma, and vasculitis] and 91 healthy controls were vaccinated. Serology for anti-H1N1 was performed by hemagglutination inhibition assay. Seroprotection rate, seroconversion rate, and factor-increase in geometric mean titer (GMT) were calculated. Adverse events were evaluated. Results. Age was comparable in patients and controls (14.8 +/- 3.0 vs 14.6 +/- 3.7 years, respectively; p = 0.47). Three weeks after immunization, seroprotection rate (81.4% vs 95.6%; p = 0.0007), seroconversion rate (74.3 vs 95.6%; p < 0.0001), and the factor-increase in GMT (12.9 vs 20.3; p = 0.012) were significantly lower in patients with juvenile ARD versus controls. Subgroup analysis revealed reduced seroconversion rates in JSLE (p < 0.0001), JIA (p = 0.008), JDM (p = 0.025), and vasculitis (p = 0.017). Seroprotection (p < 0.0001) and GMT (p < 0.0001) were decreased only in JSLE. Glucocorticoid use and lymphopenia were associated with lower seroconversion rates (60.4 vs 82.9%; p = 0.0001; and 55.6 vs 77.2%; p = 0.012). Multivariate logistic regression including diseases, lymphopenia, glucocorticoid, and immunosuppressants demonstrated that only glucocorticoid use (p = 0.012) remained significant. Conclusion. This is the largest study to demonstrate a reduced but adequate immune response to H1N1 vaccine in patients with juvenile ARD. It identified current glucocorticoid use as the major factor for decreased antibody production. The short-term safety results support its routine recommendation for patients with juvenile ARD. ClinicalTrials.gov; NCT01151644. (First Release Nov 15 2011; J Rheumatol 2012;39:167-73; doi:10.3899/jrheum.110721)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2010/10749-0]Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ) [300248/2008-3, 300665/2009-1, 301411/2009-3, 300559/2009-7]Federico FoundationButantan Foundatio

Genomics and epidemiology for gastric adenocarcinomas (GE4GAC): a Brazilian initiative to study gastric cancer

Abstract Gastric cancer (GC) is the fifth most common type of cancer worldwide with high incidences in Asia, Central, and South American countries. This patchy distribution means that GC studies are neglected by large research centers from developed countries. The need for further understanding of this complex disease, including the local importance of epidemiological factors and the rich ancestral admixture found in Brazil, stimulated the implementation of the GE4GAC project. GE4GAC aims to embrace epidemiological, clinical, molecular and microbiological data from Brazilian controls and patients with malignant and pre-malignant gastric disease. In this letter, we summarize the main goals of the project, including subject and sample accrual and current findings

Epidemia de dengue em Ribeirão Preto, SP, Brasil: nota prévia

A preliminary note on an outbreak of dengue which occurred in the city of Ribeirão Preto, State of S. Paulo, Brazil, from November 1990 to March 1991, is given. One case of Level n Dengue Hemorrhagic Fever/Dengue Shock Syndrome (DHF/DSS) and two deaths associated with dengue related shock are described. Clinicians and epidemiologists are alerted to the possibility of sporadic DHF/DSS cases during outbreaks of classical dengue in formerly free areas.Apresenta-se Nota preliminar de uma epidemia de dengue, ocorrida em Ribeirão Preto, São Paulo, Brasil, no período de novembro de 1990 a março de 1991. Descreve-se a ocorrência de um caso de "Dengue Hemorrhagic Fever/Dengue Shock Syndrome" Grau II (DHF/DSS) e de dois óbitos associados ao dengue devido a síndrome de choque. Alerta clínicos e epidemiologistas quanto à possibilidade de ocorrência de casos isolados de DHF/DSS durante epidemias de dengue clássico em áreas antes indenes à doença