298 research outputs found

    Changes in the expression of extracellular regulated kinase (ERK 1/2) in the R6/2 mouse model of Huntington's disease after phosphodiesterase IV inhibition

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    The mitogen-activated protein kinases (MAPKs) superfamily comprises three major signaling pathways: the extracellular signal-regulated protein kinases (ERKs), the c-Jun N-terminal kinases or stress-activated protein kinases (JNKs/SAPKs) and the p38 family of kinases.ERK 1/2 signaling has been implicated in a number of neurodegenerative disorders, including Huntington's disease (HD). Phosphorylation patterns of ERK 1/2 and JNK are altered in cell models of HD. In this study, we aimed at studying the correlations between ERK 1/2 and the neuronal vulnerability to HD degeneration in the R6/2 transgenic mouse model of HD. Single and double-label immunofluorescence for phospho-ERK (pERK, the activated form of ERK) and for each of the striatal neuronal markers were employed on perfusion-fixed brain sections from R6/2 and wild-type mice. Moreover, Phosphodiesterase 4 inhibition through rolipram was used to study the effects on pERK expression in the different types of striatal neurons. We completed our study with western blot analysis. Our study shows that pERK levels increase with age in the medium spiny striatal neurons and in the parvalbumin interneurons, and that rolipram counteracts such increase in pERK. Conversely, cholinergic and somatostatinergic interneurons of the striatum contain higher levels of pERK in the R6/2 mice compared to the controls. Rolipram induces an increase in pERK expression in these interneurons. Thus, our study confirms and extends the concept that the expression of phosphorylated ERK 1/2 is related to neuronal vulnerability and is implicated in the pathophysiology of cell death in HD. (C) 2012 Elsevier Inc. All rights reserved

    Predictors of response to etanercept-methotrexate treatment: a post hoc logistic regression analysis of a randomized, open-label study in Latin American patients with rheumatoid arthritis

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    Background: Determining potential predictors of clinical response would allow a more personalized rheumatoid arthritis (RA) treatment approach in heterogeneous populations such as Latin American (LA) patients. Methods: Post hoc analysis to identify baseline characteristics predictive of clinical remission in response to treatment with etanercept (ETN) plus methotrexate (MTX) in LA patients with moderate to severe MTX-resistant RA. We report data from the group of patients who received ETN 50 mg/week plus MTX (ETN + MTX, n = 281) in a clinical trial consisting of an initial 24-week open-label phase, followed by a 104-week extension. Remission was defined as 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR) score  28.5 kg/m2 (OR 3.24), disease duration > 3.7 years (OR 2.22), ESR ≤ 42 mm/h (OR 2.72), PGA ≤ 6 (OR 3.21), tender joint count ≤ 14 (OR 2.25), and total HAQ score ≤ 1.6 (OR 2.86). At Week 128, age ≤ 42 years (OR 2.21), SF-36 Mental Health Scale score > 39.6 (OR 2.16), White race (OR 4.07), > 18 swollen joints (OR 2.11), and VAS Pain ≤ 41 (OR 6.05) at baseline were the best subset of significant predictors of remission. Conclusions In LA patients with RA, younger age, higher BMI, longer disease duration, higher SF-36 Mental Health Scale score, higher swollen joint count, and overall lower disease activity predicted clinical response to ETN + MTX therapy

    AVALIAÇÃO DA DISPOSIÇÃO FINAL DE RESÍDUOS SÓLIDOS URBANOS NO MUNICÍPIO DE CIANORTE, PARANÁ.

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    In environmental management urban systems, one main problems being faced by municipalities is final disposal of municipal solid waste. Some them managed to find solutions to these problems and implemented for MSW landfills that meet the environmental and health criteria and are considered examples. In this context, this paper presents an evaluation the landfill of Cianorte City, Paraná administered by Companhia de Saneamento do Parana (SANEPAR). For this evaluation was applied the Index of Quality of Waste Landfill (IQW) which is used by the Companhia Ambiental of São Paulo (CETESB). The results showed that landfill Cianorte City presents adequate conditions to get index 9.4. However, some problems were observed regarding the site characteristics, infrastructure and operational conditions, for which some proposals in order to adapt the current system final disposal of Cianorte City.Na gestão ambiental dos sistemas urbanos, um dos principais problemas a ser enfrentado pelos municípios é a disposição final adequada dos resíduos sólidos urbanos. Alguns deles conseguiram encontrar soluções para estes problemas e implantaram aterros sanitários de resíduos sólidos domiciliares e comerciais que atendem os critérios ambientais e sanitários e são considerados exemplos. Neste contexto, este trabalho apresenta a avaliação do aterro sanitário do município de Cianorte, estado do Paraná administrado pela Companhia de Saneamento do Paraná (SANEPAR). Para esta avaliação foi aplicado o Índice de Qualidade de Aterro de Resíduos (IQR) que é utilizado pela Companhia Ambiental do Estado de São Paulo (CETESB). Os resultados obtidos demonstraram que o aterro sanitário de Cianorte apresentam condições adequadas ao apresentar índice de 9,4. Todavia, foram observados alguns problemas referentes às características do local, infraestrutura e condições operacionais, para os quais são apresentadas algumas propostas com o intuito de adequar o atual sistema de disposição final do município

    Diversidade genética em germoplasma internacional de pinhão-manso.

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    O pinhão-manso (Jatropha curcas L.) é uma oleaginosa em potencial, que tem despertado ointeresse de produtores, governos e instituições de pesquisa, visando aodesenvolvimento de tecnologia que possibilite sua utilização como cultura agroenergética

    Antibacterial Solution Using Cinnamomum verum (Cinammon) and Cympobogon citratus (Lemongrass) Essential Oils with Hydrogen Peroxide Against Staphylococcus aureus and Escherichia coli

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    Amidst the pandemic, millions of impoverished Filipinos lack sufficient access to sanitation services that protect them from bacterial infections. As such, this study endeavored to formulate a disinfectant spray of hydrogen peroxide and varying concentrations of lemongrass (Cymbopogon citratus) and cinnamon (Cinnamomum verum) essential oils to produce a maximally effective solution. Due to their natural origin, these essential oils were chosen for their extensive antibacterial properties, affordable price, and low toxicity levels. Six disinfectant spray solutions containing different concentrations of either essential oil were tested against Staphylococcus aureus and Escherichia coli bacteria through the agar disk diffusion method. After analyzing the data using mean, standard deviation, and MANOVA, it was found that including cinnamon and lemongrass essential oil had no statistically significant effect on the antibacterial activity of the hydrogen peroxide solution, regardless of the concentration of essential oil used, p \u3e 0.05. However, the lemongrass samples were slightly more effective than the cinnamon solutions. Thus, future researchers are encouraged to investigate other components that can potentially increase the antibacterial activity of a disinfectant spray

    Middle ear microbiome differences in indigenous Filipinos with chronic otitis media due to a duplication in the A2ML1 gene

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    Middle ear microbial profiles of indigenous Filipinos with chronic otitis media. All panels compare carriers with non-carriers of the A2ML1 duplication variant. Panel description: (A) ι-diversity by observed OTUs; (B) ι-diversity by the Shannon diversity index; (C) β-diversity from unweighted UniFrac principal coordinate analysis; (D) β-diversity from weighted UniFrac principal coordinate analysis. (PDF 1019 kb

    Circulating Zonulin, a Marker of Intestinal Permeability, Is Increased in Association with Obesity-Associated Insulin Resistance

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    Zonulin is the only physiological mediator known to regulate intestinal permeability reversibly by modulating intercellular tight junctions. To investigate the relationship between intestinal permeability and obesity-associated metabolic disturbances in humans, we aimed to study circulating zonulin according to obesity and insulin resistance. Circulating zonulin (ELISA) was measured in 123 caucasian men in association with inflammatory and metabolic parameters (including minimal model-measured insulin sensitivity). Circulating zonulin increased with body mass index (BMI), waist to hip ratio (WHR), fasting insulin, fasting triglycerides, uric acid and IL-6, and negatively correlated with HDL-cholesterol and insulin sensitivity. In multiple regression analysis, insulin sensitivity (p = 0.002) contributed independently to circulating zonulin variance, after controlling for the effects of BMI, fasting triglycerides and age. When circulating IL-6 was added to this model, only BMI (p = 0.01) contributed independently to circulating zonulin variance. In conclusion, the relationship between insulin sensitivity and circulating zonulin might be mediated through the obesity-related circulating IL-6 increase
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