Effects of changing ions on the crystal design, non-covalent interactions, antimicrobial activity, and molecular docking of Cu(II) complexes with a pyridoxal-hydrazone ligand.

The present work reports the influence of the presence of different ions (Cl-, Br-, NO3 -, or SO4 2-) on the formation and proprieties of Cu(II) complexes with pyridoxal-benzoylhydrazone (PLBHZ). Four new complexes were successfully synthesized, [CuCl2(PLBHZ)] (1), [CuBr2(PLBHZ)] (2), [CuCl(PLBHZ)H2O]⋅NO3⋅H2O (3), and [CuSO4(PLBHZ)H2O]⋅3H2O (4), and characterized by spectroscopic and physicochemical methods. A single-crystal X-ray study reveals the Schiff base coordinated to the metal center tridentate by the ONS-donor system, resulting in distorted square pyramidal coordination geometries. Noncovalent interactions were investigated by 3D Hirshfeld surface analysis by the d norm function, 2D fingerprint plots, and full interaction maps. The ion exchange is important in forming three-dimensional networks with π⋅⋅⋅π stacking interactions and intermolecular hydrogen bonds. The in vitro biological activity of the free ligand and metal complexes was evaluated against Gram-positive and Gram-negative bacterial strains and the free pyridoxal-hydrazone ligand showed higher activity than their Cu(II) complexes. Molecular docking was used to predict the inhibitory activity of the ligand and complexes against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli bacteria.

Organic load removal and microbial disinfection of raw domestic sewage using SrSnO3/g-C3N4 with sunlight.

Sewage treatment and water reuse are, undoubtedly, one of the main points on scientific agenda of the 21st century. Many technologies for sewage treatment are available; however, it is still as an open issue that deserves much attention in order to facilitate their application, develop more effective methods and propose alternative treatment for unusual situations. Developing high performance materials for sewage treatment fits the idea of the development of efficient and alternative methods for microorganism removal and the high organic load of wastewater and is of fundamental importance. In this paper, a heterojunction with perovskite-type strontium stannate (SrSnO3) and graphitic carbon nitride (g-C3N4) - SrSnO3/g-C3N4 - was synthesized and used for photocatalytic treatment of domestic sewage using only sunlight. Results were accompanied by assessing the total organic carbon decrease and removal of pathogenic microorganisms. X-ray diffraction and X-ray excited photoelectron spectroscopy demonstrated that a heterostructure was successfully formed and photocatalytic tests showed an important activity in the visible range, i.e., under sunlight. Exposing raw sewage to 240 min (from 11 a.m. until 3 p.m.) in the presence of SrSnO3/g-C3N4, led to a 56.1% mineralization. This process was 2.5 more efficient than photolysis under sunlight. Moreover, the treated sewage showed no coliform growth (either fecal or total) or heterotrophic bacteria. This simple treatment makes sewage suitable and safe for reuse, for example, for agriculture purposes according to Brazilian regulations criteria and could be an alternative for isolated areas in which sewage treatment plants are not available.

Tears - more to them than meets the eye: why tears are a good source of biomarkers in Parkinson's disease.

Tears are a known source of biomarkers for both ocular and systemic diseases with particular advantages; specifically, the noninvasiveness of sample collection and a unique and increasingly better-defined protein composition. Here, we discuss our rationale for use of tears for discovery of biomarkers for Parkinson's disease (PD). These reasons include literature supporting changes in tear flow and composition in PD, and the interconnections between the ocular surface system and neurons affected in PD. We highlight recent data on the identification of tear biomarkers including oligomeric α-synuclein, associated with neuronal degeneration in PD, in tears of PD patients and discuss possible sources for its release into tears. Challenges and next steps for advancing such biomarkers to clinical usage are highlighted.

Polimorfismo do gene IL1B - 511 (rs16944) em pacientes brasileiros diagnosticados com acidente vascular encefálico hemorrágico / IL1B - 511 gene polymorphism (rs16944) in Brazilian patients diagnosed with haemorrhagic stroke / Polimorfismo del gen IL1B - 511 (rs16944) en pacientes brasileños diagnosticados con accidente cerebrovascular hemorrágico

Objetivo: aferir a possível relação do polimorfismo IL1B (-511 C/T) com o prognóstico do AVEH. Método: Para avaliar este questionamento, usou-se uma amostra de 81 indivíduos diagnosticados com AVEH, na qual passaram por análise do polimorfismo IL1B -511 C/T, pela técnica da PCR-RFLP. A análise estatística adotou um nível de significância de 5%. Resultados: a pesquisa mostrou que a presença dos genótipos CC ou CT/TT não resultam uma associação estatística entre o polimorfismo da IL1B com o aparecimento do AVEH (P= 0,174). Conclusão: O estudo demonstrou que a variação de C e T no polimorfismo do gene rs16944 não está associada com os aspectos clínicos selecionados. Também mostrou não haver associação estatística com a manifestação da doença e a variação genotípica.

Objective: To assess the possible relationship between IL1B (-511 C / T) polymorphism and the prognosis of HS. Method: To evaluate this questioning, we used a sample of 81 individuals diagnosed with HS, who underwent analysis of the IL1B-511 C / T polymorphism by the PCR-RFLP technique. Statistical analysis adopted a significance level of 5%. Results: Research has shown that the presence of CC or CT / TT genotypes does not result in a statistical association between IL1B polymorphism and the appearance of HS (P = 0.174). Conclusion: The study demonstrated that C and T variation in rs16944 gene polymorphism is not associated with the selected clinical aspects. It also showed no statistical association with disease manifestation and genotypic variation.

Objetivo: evaluar la posible relación entre el polimorfismo IL1B (-511 C / T) y el pronóstico de AVEH. Método: Para evaluar este cuestionamiento, utilizamos una muestra de 81 individuos diagnosticados con AHV, que se sometieron a análisis del polimorfismo IL1B-511 C / T mediante la técnica PCR-RFLP. El análisis estadístico adoptó un nivel de significación del 5%. Resultados: La investigación ha demostrado que la presencia de genotipos CC o CT / TT no da como resultado una asociación estadística entre el polimorfismo IL1B y la aparición de AVEH (P = 0.174). Conclusión: El estudio demostró que la variación de C y T en el polimorfismo del gen rs16944 no está asociada con los aspectos clínicos seleccionados. Tampoco mostró asociación estadística con la manifestación de la enfermedad y la variación genotípica.

Associação do polimorfismo genético no gene BCL2 no Acidente Vascular Cerebral Hemorrágico/Aneurisma / Association of genetic polymorphism in the BCL2 gene in/with Hemorrhagic Stroke/Aneurysm / Asociación de polimorfismo genético en el gen BCL2 en/con el accidente cerebrovascular hemorrágico/aneurisma

Objetivo: Verificar a distribuição do polimorfismo do gene BCL2 (rs1801018), em sua região codante, em pacientes portadores de Acidente Vascular Cerebral Hemorrágico (AVCh)/Aneurisma. Além de associar o presente polimorfismo as manifestações clinicas da doença. Método: O estudo foi conduzido com 158 participantes de pesquisa. Os grupos foram pareados quanto ao sexo e idade. A genotipagem foi conduzida pela técnica PCR-RFLP. Após o cálculo das frequências alélicas e genotípicas de cada grupo, foram utilizados testes estatísticos apropriados para cada tipo de comparação. O nível de significância adotado foi de 5%. Resultados: Os dados indicaram que a frequência dos genótipos apresentou uma diferença estatisticamente significante entre o grupo caso e controle, encontrando-se o genótipo ala43ala na maioria dos participantes de ambos os grupos. Conclusão: A presença do alelo mutante (trh) foi vista como um fator protetor para AVCh/aneurisma. Porém, estudos em outras populações devem ser realizados para se obter uma melhor compreensão sobre a doença AVCh/aneurisma.

Objective: Verify the distribution of the BCL2 gene polymorphism (rs1801018), located in its coding region, in patients with Hemorrhagic Stroke (HS)/Aneurysm (A). Furthermore, to associate this polymorphism with the HS/A clinical manifestations. Method: The study was conducted with 158 research participants and the groups matched by sex and age. Genotyping was done by the PCR-RFLP technique. After calculating the allele and genotype frequencies of each group, appropriate statistical tests were performed for each comparison type with the adopted significance level of 5%. Results: The data indicated that the frequency of the genotypes showed a statistically significant difference between the case and control group, and the ala43ala genotype was found in most participants in both groups. Conclusion: The presence of the mutant allele (trh) was observed as a protective factor for HS/A. However, studies in other populations should be performed to obtain a better understanding of this disease.

Objetivo: Objetivo: Verificar la distribución del polimorfismo del gen BCL2 (rs1801018), en ubicado su región de codificación, en pacientes con accidente cerebrovascular hemorrágico (ACVh)/aneurisma. Asimismo, asociar el presente polimorfismo con las manifestaciones clínicas de la enfermedad. Método: El estudio se realizó con 158 participantes, y los grupos fueron agrupados por sexo y edad. La determinación del genotipo se realizó mediante la técnica PCR-RFLP. Después de calcular las frecuencias de alelos y genotipos de cada grupo, se realizaron pruebas estadísticas apropiadas para cada tipo de comparación con el nivel de significación adoptado de 5%. Resultados: Los datos indicaron que la frecuencia de los genotipos mostró una diferencia estadísticamente significativa entre el grupo caso y el control, con el genotipo ala43ala encontrado en la mayoría de los participantes de ambos grupos. Conclusión: La presencia del alelo mutante (trh) fue visto como un factor protector para el ACVh/aneurisma. Sin embargo, se deben realizar más estudios en otras poblaciones para obtener una mejor comprensión de la enfermedad de ACVh/aneurisma.

Evaluation of the antimicrobial activity of silver nanoparticles obtained by microwave-assisted green synthesis using Handroanthus impetiginosus (Mart. ex DC.) Mattos underbark extract.

We describe here a green method for the preparation of silver nanoparticles (AgNPs), by a microwave-assisted synthesis route using Handroanthus impetiginosus underbark extract, with antibacterial activity. After optimizing the synthesis parameters with a Box-Benhken designed experiment, samples were characterized by powder XRD, TEM, UV-Vis spectroscopy, FTIR and zetametry. Using the overall optimized conditions of synthesis - time of reaction 15 min at 200 °C and plant extract/AgNO3 volume ratio equal to 10% - highly crystalline ∼13.4 nm-sized spherical AgNPs in a well-dispersed colloidal state were obtained. It was also proved that the plant extract compounds act as reductant and capping agents during synthesis to functionalize AgNPs, resulting in a negatively charged surface with high values of zeta potential in a wide range of pH, from acidic to alkaline media. Biological activity tests against Staphylococcus aureus and Escherichia coli and cell viability experiments showed that synthesized AgNPs were not toxic to HaCaT mammalian cells and presented a high efficiency against Gram-positive bacteria (S. aureus). This was associated with the synergistic combination of AgNP silver cores with the capping layer containing natural compounds with antimicrobial properties and considered an alternative to the AgNPs commonly obtained from conventional routes that present antibacterial effectiveness preferentially against Gram-negative strains.

Statistical association of rs2243250 polymorphism of IL4 gene and hemorrhagic stroke in Brazilian population / Associação estatística entre o polimorfismo rs2243250 no gene da IL-4 e o AVC hemorrágico na população brasileira

ABSTRACT Interleukin-4 (IL-4) has great significance in inflammatory processes in cases of stroke, since it is able to polarize microglia to the antiinflammatory phenotype called M2. This study analyzed if the variation between TT genotype and the other genotypes (CT and CC), in -589 (rs2243250) polymorphism of IL4 gene, has association with the prognosis of hemorrhagic stroke (HS) and with clinical aspects which are risk factors for cerebrovascular diseases. The result of this study shows that there is no statistical association of the IL4 polymorphism with either prognosis or clinical aspects in HS patients.

RESUMEN La interleucina-4 (IL-4) tiene gran importancia en los procesos inflamatorios en casos de accidente cerebrovascular (ACV), puesto que hace que las microglías sean polarizadas hacia el fenotipo antiinflamatorio M2. Este estudio analizó si la variación entre el genotipo TT y los demás genotipos (CT y CC), en el polimorfismo -589 (rs2243250) del gen IL4, posee asociación con el pronóstico de ACV hemorrágico y con aspectos clínicos que son factores de riesgo para enfermedades cerebrovasculares. El resultado de este estudio enseña que no hay asociación estadística del polimorfismo del IL4 ni con el pronóstico ni con los aspectos clínicos de pacientes con ACV hemorrágico.

RESUMO A interleucina-4 (IL-4) tem grande importância nos processos inflamatórios em casos de acidente vascular cerebral (AVC), uma vez que ela é capaz de polarizar micróglias para o fenótipo anti-inflamatório chamado M2. Este estudo analisou se a variação entre o genótipo TT e os demais genótipos (CT e CC), no polimorfismo -589 (rs2243250) do gene IL4, possui associação com o prognóstico de AVC hemorrágico e com aspectos clínicos que são fatores de risco para doenças cerebrovasculares. O resultado deste estudo mostra que não há associação estatística do polimorfismo do IL4 nem com prognóstico nem com os aspectos clínicos dos pacientes com AVC hemorrágico.

Association of the CHGA gene polymorphism in patients with hemorrhagic stroke and/or aneurysm / Associação do polimorfismo do gene CHGA em pacientes com acidente vascular encefálico hemorrágico e/ou aneurisma

ABSTRACT Introduction: Cerebrovascular diseases have been associated with several genes. Chromogranin A (CHGA) has been used as maker in cardiovascular disease. Therefore, evaluating the polymorphism and verifying its association with this pathology is very important to better understand this disease. Objective: The aim of this study was to identify the association between coding region polymorphism in -264 position of the CHGA gene (Glu264Asp) and hemorrhagic stroke (HS)/aneurysm in the Federal District, Brazil. Methods: This is a population-based case-control, involving 45 cases with HS and/or aneurysm. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method is used for genotyping these samples. A significance level of 5% was adopted. Results: The absence of the CC genotype the Glu264Asp CHGA polymorphism in the study participants and the significant presence of the GC heterozygote genotype were observed in this study. However, the distribution of genotypes did not differ statistically in the groups. Conclusion: The Glu264Asp CHGA polymorphism does not seem to contribute to the genesis of the CHGA protein expression in this patients group, but to understand whether or not there is a possible association of the pathology in question and whether the mutation will contribute in the gene therapy and thus to improve patients' quality of life.

RESUMEN Introducción: Enfermedades cerebrovasculares han sido vinculadas a diversos genes. La cromogranina A (CgA) es utilizada como un marcador en enfermedades cardiovasculares. Por consiguiente, evaluar el polimorfismo y verificar la asociación con esa patología es muy importante para la mejor comprensión de la enfermedad. Objetivo: El enfoque del ensayo fue identificar la asociación entre el polimorfismo en la región codificante en la posición -264 del gen CHGA (Glu264Asp) y el accidente cerebrovascular hemorrágico (ACVH)/aneurisma en Distrito Federal, Brasil. Métodos: Estudio de caso-control de base poblacional, involucrando 45 casos con ACVH y/o aneurisma. Para el genotipaje de las muestras, se utilizó la técnica de laboratorio reacción en cadena de la polimerasa-polimorfismos en la longitud de los fragmentos de restricción (PCR-RFLP). Nivel de significación elegido: 5%. Resultados: Ausencia del genotipo CC del polimorfismo Glu264Asp CHGA en los participantes del ensayo y presencia significativa del genotipo heterocigoto GC. Sin embargo, la distribución de los genotipos no difirió estadísticamente en los grupos. Conclusión: El polimorfismo Glu264Asp CHGA parece no contribuir para la génesis de la expresión de la proteína CgA en este grupo de pacientes, pero revelar si existe o no una posible asociación de la patología en cuestión y si la mutación contribuirá para la terapia genética y mejorará la calidad de vida de los pacientes.

RESUMO Introdução: Doenças cerebrovasculares têm sido ligadas a diversos genes. A cromogranina A (CHGA) é utilizada como um marcador em doenças cardiovasculares. Portanto, avaliar o polimorfismo e verificar a associação com essa patologia é muito importante para melhor compreensão dessa doença. Objetivo: O foco do estudo foi identificar a associação entre o polimorfismo na região codante posição -264 do gene CHGA (Glu264Asp) e o acidente vascular encefálico hemorrágico (AVEH)/aneurisma no Distrito Federal, Brasil. Métodos: Estudo caso-controle de base populacional, envolvendo 45 casos com AVEH e/ou aneurisma. Para a genotipagem dessas amostras, utilizou-se a técnica laboratorial reação em cadeia da polimerase-polimorfismo de comprimento de fragmento de limitação (PCR-RFLP). Nível de significância de 5% foi adotado. Resultados: A ausência do genótipo CC do polimorfismo Glu264Asp CHGA nos participantes do estudo e a presença significativa do genótipo heterozigoto GC foram verificadas. No entanto, a distribuição dos genótipos não diferiu estatisticamente nos grupos. Conclusão: O polimorfismo Glu264Asp CHGA parece não contribuir para a gênese da expressão da proteína CHGA nesse grupo de pacientes, mas revela se existe ou não uma possível associação da patologia em questão e se a mutação contribuirá para a terapia gênica e melhorará a qualidade de vida dos pacientes.

Levels of oligomeric α-Synuclein in reflex tears distinguish Parkinson's disease patients from healthy controls.

Aim: Due to active engagement of sensory and afferent nerve fibers in reflex tearing which could be affected in Parkinson's disease (PD), we tested reflex tears as a source of potential PD biomarkers. Patients & methods: Reflex tears collected from 84 PD and 84 age- and sex-equivalent healthy controls (HC) were used to measure levels of oligomeric α-Syn (α-SynOligo), total α-Syn (α-SynTotal), CCL2, DJ-1, lactoferrin and MMP9. Results: α-synOligo (p < 0.0001), CCL2 (p = 0.003) and lactoferrin (p = 0.002) were significantly elevated in PD patient tears relative to HC tears. Tear flow was significantly lower in PD relative to HC (p = 0.001). Conclusion: Reflex tears are a potential source for detection of characteristic changes in PD patients.

Oligomeric α-synuclein is increased in basal tears of Parkinson's patients.

Aim: Secretion of proteins into basal tears of Parkinson's disease (PD) patients may be altered by changes in nerve function. Materials & methods: Oligomeric α-SynOligo and total α-SynTotal, CCL-2, DJ-1, LF and MMP-9 were measured in basal tears from 93 PD patients and 82 age- and sex-equivalent healthy controls. Results: α-SynTotal was decreased (p = 0.0043), whereas α-SynOligo (p < 0.0001) and the ratio of α-SynOligo/α-SynTotal (p < 0.0001) were increased in basal tears from PD patients compared with healthy controls. Area under receiver-operating curves of α-SynOligo and α-SynOligo/α-SynTotal contents were 0.70 (95% confidence limits: 0.621-0.774) and 0.72 (95% confidence limits: 0.642-0.792). Conclusion: PD patient basal tears may contain biomarkers that can be assayed noninvasively and inexpensively.

P2X7 Receptor Antagonist A804598 Inhibits Inflammation in Brain and Liver in C57BL/6J Mice Exposed to Chronic Ethanol and High Fat Diet.

Chronic low-grade neuroinflammation is increasingly implicated in organ damage caused by alcohol abuse. Purinergic P2X7 receptors (P2X7Rs) play an important role in the generation of inflammatory responses during a number of CNS pathologies as evidenced from studies using pharmacological inhibition approach. P2X7Rs antagonism has not been tested during chronic alcohol abuse. In the present study, we tested the potential of P2X7R antagonist A804598 to reduce/abolish alcohol-induced neuroinflammation using chronic intragastric ethanol infusion and high-fat diet (Hybrid) in C57BL/6J mice. We have previously demonstrated an increase in neuroinflammatory response in 8 weeks of Hybrid paradigm. In the present study, we found neuroinflammatory response to 4 weeks of Hybrid exposure. A804598 treatment reversed the changes in microglia and astrocytes, reduced/abolished increases in mRNA levels of number of inflammatory markers, including IL-1ß, iNOS, CXCR2, and components of inflammatory signaling pathways, such as TLR2, CASP1, NF-kB1 and CREB1, as well in the protein levels of pro-IL-1ß and Nf-kB1. The P2X7R antagonist did not affect the increase in mRNA levels of fraktalkine (CX3CL1) and its receptor CX3CR1, an interaction that plays a neuroprotective role in neuron-glia communication. P2X7R antagonism also resulted in reduction of the inflammatory markers but did not alter steatosis in the liver. Taken together, these findings demonstrate how P2X7R antagonism suppresses inflammatory response in brain and liver but does not alter the neuroprotective response caused by Hybrid exposure. Overall, these findings support an important role of P2X7Rs in inflammation in brain and liver caused by combined chronic alcohol and high-fat diet. Graphical Abstract ᅟ.

TNFA gene in Brazilian patients with hemorrhagic stroke or cerebral aneurysm / Gene TNFA em pacientes brasileiros com acidente vascular encefálico hemorrágico ou aneurisma cerebral

ABSTRACT Introduction: Many cerebrovascular diseases display a relation with inflammatory processes. Furthermore, the influence of several polymorphisms has been studied to improve the knowledge of physiological mechanisms of the nervous system. Objectives: The aim of this study was to identify if there was an association between a polymorphism in -308 position of the TNFA gene and the development of hemorrhagic stroke or aneurysm in Distrito Federal, Brazil. Methods: We collected the clinical information and the medical records from hemorrhagic stroke or aneurysm patients. The occurrence of stroke or aneurysm was confirmed by computed tomography (CT) or magnetic resonance image (MRI). The TNFA genotypes were determined by polymerase chain reaction restriction fragment length polymorphism. Results: The AG genotype appears to decrease the occurrence of hemorrhagic stroke or aneurysm in people between 45-63 years. Our study was the first to investigate this association in a Brazilian sample, although a previous report showed a similar effect with ischemic stroke in a Chinese population. Conclusion: The TNFA -308 AG genotype is associated with a decreased risk of aneurysm or hemorrhagic stroke in a population from the capital of Brazil, Distrito Federal.

RESUMO Introdução: Muitas doenças cerebrovasculares relacionam-se com processos inflamatórios, portanto, a influência de vários polimorfismos em doenças tem sido estudada para melhorar o conhecimento sobre os mecanismos fisiológicos do sistema nervoso. Objetivo: Identificar a associação entre um polimorfismo na posição -308 do gene TNFA e o desenvolvimento de acidente vascular encefálico hemorrágico (AVEH) ou aneurisma em pacientes de uma base hospitalar do Distrito Federal, Brasil. Métodos: Foram coletados os prontuários e as informações clínicas de pacientes com AVEH ou aneurisma. A caracterização dos grupos caso foi confirmada por tomografia computadorizada (TC) ou ressonância nuclear magnética (RNM). Os genótipos do gene TNFA foram determinados por técnica do polimorfismo de comprimento dos fragmentos de restrição do produto obtido pela reação em cadeia da polimerase (PCR). Resultados: O genótipo AG parece diminuir a ocorrência de AVEH ou aneurisma em indivíduos entre 45 e 63 anos. Nosso estudo foi o primeiro a investigar essa associação em uma amostra brasileira, embora um relatório anterior tenha mostrado efeito semelhante com o acidente vascular encefálico isquêmico em uma população chinesa. Conclusão: O genótipo TNFA -308 AG está associado à diminuição do risco de aneurisma ou AVEH em uma população da capital do Brasil, Distrito Federal.

Taste masking and rheology improvement of drug complexed with beta-cyclodextrin and hydroxypropyl-ß-cyclodextrin by hot-melt extrusion.

This study aimed to mask fluconazole (FLU) taste and improve its rheological properties by an efficient process of cyclodextrin complexation. For this, hot-melt extrusion (HME) was used to obtain extrudates composed of FLU, hydroxypropylcellulose, and one of two different cyclodextrins (ß-cyclodextrin or hydroxypropyl-ß-cyclodextrin) maintaining the drug:cyclodextrin molar ratio at 1:0.3 or 1:0.2, respectively. Samples were characterized by physicochemical tests, palatability using e-tongue and antifungal assays. Drug stability was preserved after HME, according to spectroscopy test (correlation coefficient >0.9) and HPLC-assay (100-107%). Flowability was improved in HME systems with compressibility of <12%. Similarly, floodability exhibited significant enhancement (dispersibility <10%). Whereas extrudates of FLU containing only the polymeric matrix led to a slow drug dissolution efficiency (18.6%) and a partial drug taste masking; extrudates containing cyclodextrin accelerated FLU dissolution (dissolution efficiency approx. 30%) and provided a complete drug taste masking. Moreover, HME process could produce drug complexes with high complexation efficiency and preserve its antifungal activity.

Analysis of 18 bp Ins/Del at -2549 polymorphism of the vascular endothelial growth factor gene in patients with systemic lupus erythematosus / Análise do polimorfismo -2549 18 pb Ins/Del do gene do fator de crescimento vascular endotelial em indivíduos com lúpus eritematoso sistêmico

ABSTRACT Systemic lupus erythematosus (SLE) is considered an autoimmune disease characterized by the action of autoantibodies, which cause chronic inflammation in various tissues of the body. Considering the vascular endothelial growth factor (VEGF) participation in the development of inflammation, this study aimed to evaluate the frequency of the polymorphism at the -2549 position (Ins/Del 18pb, rs35569394) in patients with SLE and in healthy individuals. No statistical differences were found when comparing the allele and genotype frequencies between patients and controls, suggesting that there is no association between the studied polymorphism and the development of SLE.

RESUMO O lúpus eritematoso sistêmico (LES) é considerado uma doença autoimune devido à atuação de autoanticorpos, que ocasionam inflamações crônicas em diversos tecidos corporais. Considerando o envolvimento do fator de crescimento vascular endotelial (VEGF) no desenvolvimento da inflamação, este trabalho objetivou avaliar a frequência do polimorfismo na posição -2549 (Ins/Del 18pb, rs35569394) em pacientes com LES, comparando-os com indivíduos saudáveis. Não foram encontradas diferenças estatísticas ao comparar as frequências alélicas e genotípicas entre pacientes e controles, sugerindo que não há associação entre o desenvolvimento de LES e o polimorfismo estudado.

Avaliação microbiológica de couve minimamente processada comercializada nos supermercados de Brasília ­ DF / Microbiological evaluation of minimally processed brassica commercialized in the supermarkets of Brasília - DF

No Brasil, a couve minimamente processada é comercializada durante todo o ano e geralmente é considerada segura para o consumo pelos consumidores. Este estudo avaliou a qualidade microbiológica de seis diferentes marcas de couve minimamente processada comercializadas em supermercados de Brasília. As análises realizadas foram: contagem total de bactérias mesófilas e psicrotróficas, determinação de coliformes totais e coliformes termotolerantes e identificação molecular de E. coli, Salmonella spp. e L. monocytogenes por sequenciamento de DNA. Os resultados revelaram que as amostras de couve minimamente processada apresentaram baixa qualidade microbiológica. Coliformes termotolerantes foram encontrados em todas as amostras de couve minimamente processada, com populações superiores a 2 log NMP/g em metade das amostras. Após o sequenciamento de DNA, E. coli O157:H7 foi identificada em 2 das 6 amostras e Salmonella enteritidis foi identificada em 1 das 6 amostras. Listeria monocytogenes foi encontrada em metade das amostras, sendo que a presença desta bactéria é geralmente associada a um período excessivo de armazenamento ou estocagem em temperaturas abusivas. Estes resultados mostraram que a couve minimamente processada exposta ao consumo nos supermercados de Brasília pode ser um veículo para a transmissão de bactérias patogênicas e indicaram a necessidade de melhorar a qualidade na cadeia de produção dos vegetais minimamente processados para garantir a vida útil e a segurança microbiológica desses produtos.(AU)

Anxiolytic-like effect of a novel peptide isolated from the venom of the social wasp Synoeca surinama.

Pathological anxiety is among the most common psychiatric illnesses, but current treatment is highly limited. In this study, we investigated the potential anxiolytic-like effects of a peptide isolated from Synoeca surinama venom. Rats treated with this peptide spent more time exploring the open arms of elevated plus maze, which indicates an anxiolytic-like profile for this peptide. This study is the first to show the pharmacological use of S. surinama venom in the treatment of anxiety.

In Silico Modeling of Novel Drug Ligands for Treatment of Concussion Associated Tauopathy.

The objective of this study was to develop an in silico screening model for characterization of potential novel ligands from commercial drug libraries able to functionally activate certain olfactory receptors (ORs), which are members of the class A rhodopsin-like family of G protein couple receptors (GPCRs), in the brain of murine models of concussion. We previously found that concussions may significantly influence expression of certain ORs, for example, OR4M1 in subjects with a history of concussion/traumatic brain injury (TBI). In this study, we built a 3-D OR4M1 model and used it in in silico screening of potential novel ligands from commercial drug libraries. We report that in vitro activation of OR4M1 with the commercially available ZINC library compound 10915775 led to a significant attenuation of abnormal tau phosphorylation in embryonic cortico-hippocampal neuronal cultures derived from NSE-OR4M1 transgenic mice, possibly through modulation of the JNK signaling pathway. The attenuation of abnormal tau phosphorylation was rather selective since ZINC10915775 significantly decreased tau phosphorylation on tau Ser202/T205 (AT8 epitope) and tau Thr212/Ser214 (AT100 epitope), but not on tau Ser396/404 (PHF-1 epitope). Moreover, no response of ZINC10915775 was found in control hippocampal neuronal cultures derived from wild type littermates. Our in silico model provides novel means to pharmacologically modulate select ubiquitously expressed ORs in the brain through high affinity ligand activation to prevent and eventually to treat concussion induced down regulation of ORs and subsequent cascade of tau pathology. J. Cell. Biochem. 117: 2241-2248, 2016. © 2016 Wiley Periodicals, Inc.

Pathophysiological effects caused by the venom of the social wasp Synoeca surinama.

Envenomation by wasp stings is a public health preoccupation, and signals after stings have variable effects depending on the number of attacks and individual sensitivities. Even with the high rate of wasp sting cases, the study of phatophysiological effects of the envenomation is still very incipient. In this context, early and accurate assessment of this prognostic can aid in the reduction of the symptomatology and complete remission of the later symptoms. Then, the present study evaluated the toxicological effects caused by envenomation produced by Synoeca surinama, a wasp easily found in Neotropical regions. In vivo tests comprised the evaluation of LD50 (OECD 423), nociception, edema, myotoxic lesion and hemorrhage induction, in vitro tests were realized to evaluate hemolysis, contractile and coagulation alteration. The envenomation effects observed were dose- and time-dependent; the LD50 observed for S. surinama was 178 µg/kg, approximately 17 times more lethal than that of the honeybee. Moreover, a potent algesic and oedema effect, and weak hemorrhagic signal were observed after injection of the venom wasp. Assays in vitro showed that this venom is able to prolong the clotting time of plasma and to increase creatine kinase levels. Our results demonstrated that this venom induced serious local and systemic effects in mammals and, so, to avoid permanent damage to the patient, health professionals should carefully investigate each accident. Moreover, due to its high occurrence in Neotropical regions, ecological management, particularly in areas with free access of children and elderly, should be performed.

Novel application of brain-targeting polyphenol compounds in sleep deprivation-induced cognitive dysfunction.

Sleep deprivation produces deficits in hippocampal synaptic plasticity and hippocampal-dependent memory storage. Recent evidence suggests that sleep deprivation disrupts memory consolidation through multiple mechanisms, including the down-regulation of the cAMP-response element-binding protein (CREB) and of mammalian target of rapamycin (mTOR) signaling. In this study, we tested the effects of a Bioactive Dietary Polyphenol Preparation (BDPP), comprised of grape seed polyphenol extract, Concord grape juice, and resveratrol, on the attenuation of sleep deprivation-induced cognitive impairment. We found that BDPP significantly improves sleep deprivation-induced contextual memory deficits, possibly through the activation of CREB and mTOR signaling pathways. We also identified brain-available polyphenol metabolites from BDPP, among which quercetin-3-O-glucuronide activates CREB signaling and malvidin-3-O-glucoside activates mTOR signaling. In combination, quercetin and malvidin-glucoside significantly attenuated sleep deprivation-induced cognitive impairment in -a mouse model of acute sleep deprivation. Our data suggests the feasibility of using select brain-targeting polyphenol compounds derived from BDPP as potential therapeutic agents in promoting resilience against sleep deprivation-induced cognitive dysfunction.