Synthesis, antiangiogenesis evaluation and molecular docking studies of 1-Aryl-3-[(thieno[3,2-b]pyridin-7-ylthio)phenyl]ureas: Discovery of a new substitution pattern for type II VEGFR-2 Tyr kinase inhibitors

The synthesis and biological evaluation of novel 1-aryl-3-[2-, 3- or 4-(thieno[3,2-b]pyridin-7-ylthio)phenyl]ureas 3, 4 and 5 as VEGFR-2 tyrosine kinase inhibitors, are reported. The 1-aryl-3-[3-(thieno[3,2-b]pyridin-7-ylthio)phenyl]ureas 4a-4h, with the arylurea in the meta position to the thioether, showed the lowest IC50 values in enzymatic assays (10-206 nM), the most potent compounds 4d-4h (IC50 10-28 nM) bearing hydrophobic groups (Me, F, CF3 and Cl) in the terminal phenyl ring. A convincing rationalization was achieved for the highest potent compounds 4 as type II VEGFR-2 inhibitors, based on the simultaneous presence of: (1) the thioether linker and (2) the arylurea moiety in the meta position. For compounds 4, significant inhibition of Human Umbilical Vein Endothelial Cells (HUVECs) proliferation (BrdU assay), migration (wound-healing assay) and tube formation were observed at low concentrations. These compounds have also shown to increase apoptosis using the TUNEL assay. Immunostaining for total and phosphorylated (active) VEGFR-2 was performed by Western blotting. The phosphorylation of the receptor was significantly inhibited at 1.0 and 2.5 microM for the most promising compounds. Altogether, these findings point to an antiangiogenic effect in HUVECs.

Experimental and numerical studies of hybrid PCM embedded in plastering mortar for enhanced thermal behaviour of buildings

This paper proposes a methodology for improvement of energy efficiency in buildings through the innovative simultaneous incorporation of three distinct phase change materials (here termed as hybrid PCM) in plastering mortars for façade walls. The thermal performance of a hybrid PCM mortar was experimentally evaluated by comparing the behaviour of a prototype test cell (including hybrid PCM plastering mortar) subjected to realistic daily temperature profiles, with the behaviour of a similar prototype test cell, in which no PCM was added. A numerical simulation model was employed (using ANSYS-FLUENT) to validate the capacity of simulating temperature evolution within the prototype containing hybrid PCM, as well as to understand the contribution of hybrid PCM to energy efficiency. Incorporation of hybrid PCM into plastering mortars was found to have the potential to significantly reduce heating/cooling temperature demands for maintaining the interior temperature within comfort levels when compared to normal mortars (without PCM), or even mortars comprising a single type of PCM.

In vitro and in vivo studies of temozolomide loading in zeolite structures as drug delivery systems for glioblastoma

Zeolites Y (faujasite) and MOR (mordonite) were used as hosts for temozolomide (TMZ), a current good-standard chemotherapeutic agent used in the treatment of glioblastoma brain tumors. TMZ was loaded into zeolites by liquid-phase adsorption at controlled pH. FTIR, 1H NMR, MS, SEM, UV/vis and chemical analysis demonstrated the successful loading of TMZ into zeolite hosts. The hydrolysis of TMZ in MTIC (TMZ metabolite) after the preparation of drug delivery systems (DDS) was observed in simulated body fluid. The effect of zeolites and DDS were evaluated on the viability of glioblastoma cell lines. Unloaded Y zeolite presented toxicity to cancer cells in contrast to MOR. In accordance, the best results in potentiation of the TMZ effect was obtained with MOR. We found that mordonite loaded with 0.026 mmol of TMZ was able to decrease the half maximal inhibitory concentrations (IC50) at least 3-fold in comparison to free temozolomide both in vitro and in vivo.

Looking for mechanisms regulating lung growth in CDH: rat and human studies

Tese de Doutoramento em Ciências da Saúde

Hormonal, metabolic and nutritional alterations in smokers: emergency for smoking abstinence

OBJECTIVE: To evaluate the biochemical and nutritional status of smokers in treatment for smoking cessation and its association with anthropometric parameters. METHODS: This is a cross-sectional study with convenience sample. Adult smokers were assessed at the start of treatment in the Interdisciplinary Center for Tobacco Research and Intervention of the University Hospital of the Federal University of Juiz de Fora (CIPIT/HU-UFJF). We evaluated the body mass index (BMI), conicity index (CI); waist circumference (WC), percentage of body fat (%BF), fasting glycemia, cortisol, insulin, total cholesterol (TC), LDL-c, HDL-c, triglycerides (TG) and metabolic syndrome (MS). RESULTS: Most participants (52.2%) had MS and high cardiovascular risk. The fasting glycemia was abnormal in 30.4%. There was a significant positive correlation between BMI and WC (r = 0.90; p = 0.0001), %BF (r = 0.79; p = 0.0001), CI (r = 0.65; p = 0.0001), glycemia (r = 0.42; p = 0.04) and TG (r = 0.47; p = 0.002). The CI presented positive correction with insulin (r = 0.60; p = 0.001), glycemia (r = 0.55; p = 0.007), TG (r = 0.54; p = 0.008) and %BF (r = 0.43; p = 0.004). Patients with longer duration of smoking had a higher risk of developing MS (OR = 9.6, p = 0.016). CONCLUSION: The smokers evaluated had increased risk for developing MS, especially those with longer duration of smoking, requiring urgent smoking cessation.

A qualidade de vida da pessoa com doença renal crónica em programa regular de hemodiálise

Dissertação de mestrado em Enfermagem

Effects of bariatric surgery on the central nervous system and eating behavior in humans: a systematic review on the neuroimaging studies

INTRODUCTION: Neuroimaging studies suggest that obese people might show hyperactivity of brain areas regarding reward processing, and hypoactivity of brain areas concerning cognitive control, when exposed to food cues. Although the effects of bariatric surgery on the central nervous system and eating behavior are well known, few studies have used neuroimage techniques with the aim of investigating the central effects of bariatric surgery in humans. OBJECTIVES: This paper systematically and critically reviews studies using functional neuroimaging to investigate changes on the patterns of activation of central areas related to the regulation of eating behavior after bariatric surgery. METHOD: A search on the databases Medline, Web of Science, Lilacs and Science Direct on Line, was conducted in February 2013, using the keywords "Neuroimaging", "Positron-Emission Tomography", "Magnetic Resonance Imaging", "Gastric Bypass", "Gastroplasty", "Jejunoileal Bypass", "Bariatric Surgery". RESULTS: Seven manuscripts were included; the great majority studied the central effects of Roux en Y gastric bypass, using positron emission tomography or functional magnetic resonance. CONCLUSIONS: Bariatric surgery might normalize the activity of central areas concerned with reward and incentive salience processing, as the nucleus accumbens and mesencephalic tegmental ventral area, as well as circuitries processing behavioral inhibition, as the dorsolateral prefrontal cortex.

Psychometric properties of assessment instruments for autism spectrum disorder: a systematic review of Brazilian studies

Objective To systematically review the scientific literature on the psychometric properties of international instruments for the assessment of autism spectrum disorder (ASD) in the Brazilian population. Methods A search of bibliographic references was conducted in six electronic databases: PsycINFO, PubMed, IndexPsi, Lilacs, Capes (theses and dissertations) and SciELO. The studies were selected by two independent researchers. Results The procedure identified 11 studies of the Brazilian population that encompassed six ASD assessment tools. Given the information provided, the adaptation of the M-CHAT, a screening instrument, was the best conducted. All steps of the adaptation process were described and the changes made to the final version of the instrument were presented, which was not addressed in other studies. In terms of reliability, all of the instruments that assessed internal consistency showed adequate values. In addition, the ADI-R and the CARS adaptations also satisfactorily contemplated inter-rater reliability and test-retest indices, respectively. Finally, all studies aiming to validate instruments showed evidence of validity and sensitivity, and specificity values above 0.90 were observed in the ASQ, ADI-R and ABC. Conclusion Considering both the psychometric aspects and the copyright information, the screening instrument that currently appears to be best indicated for clinical and research use is the M-CHAT. It was also noticed that there are still no specific ASD diagnostic tools available for use in Brazil. This lack of diagnostic instruments consists in a critical situation for the improvement of clinical practice and the development of research in this area.

Cultural studies as the new humanities

The purpose of this study is to argue that Cultural Studies may be regarded as the new humanities. Cultural Studies focus on ethnic, post-colonial, communication, anthropological, ethnographic and feminist studies, and only ‘very marginally’ have they shown an interest in literature and literary studies (Aguiar & Silva, 2008). But those fields, which ‘Social Science’ rather than the ‘Arts’ have invested in (Ibid., p. 254), are the touchstone of modernity. Today, the concept we have of humankind is, to a large extent, played out in these areas. The questioning of both humankind and modernity has as backdrop the technologically-driven shift of culture from word to image (Martins, 2011 a). My proposal takes into account this debate, while underscoring how Cultural Studies are engaged in what is current and contemporary, which means, in the present and everyday life.

Cognitive-behavioral therapy for anxiety disorders in children and adolescents: a systematic review of follow-up studies

Objective To conduct a systematic review about the long-term response to cognitive-behavioral therapy (CBT) for anxiety disorders (ADs) in children and adolescents. Methods The PubMed and ISI Web of Science databases were consulted. Search in the databases was performed in November 2012 and included cohort studies after CBT for ADs in children and adolescents with a follow-up period over 12 months. Results A total of 10 papers met the inclusion criteria. The follow-up period ranged from 12 months to 13 years and the results generally showed maintenance of the short-term benefits with CBT. However, the studies presented limitations, especially regarding methods, such as lack of a control group and losses to follow-up. Conclusion The long-term benefits of CBT were identified, however it would be interesting to conduct other studies with more frequent assessment periods, in order to minimize losses to follow-up, in addition to evaluating children and adolescents in the various stages of their development.

Fundamental studies on natural deep eutectic solvents: physico-chemical, thermal and rheological properties

When combined at particular molar fractions, sugars, aminoacids or organic acids a present a high melting point depression, becoming liquids at room temperature. These are called Natural Deep Eutectic Solvents – NADES and are envisaged to play a major role on the chemical engineering processes of the future. Nonetheless, there is a significant lack of knowledge of its fundamental and basic properties, which is hindering their industrial applications. For this reason it is important to extend the knowledge on these systems, boosting their application development [1]. In this work, we have developed and characterized NADES based on choline chloride, organic acids, amino acids and sugars. Their density, thermal behavior, conductivity and polarity were assessed for different compositions. The conductivity was measured from 0 to 40 °C and the temperature effect was well described by the Vogel-Fulcher-Tammann equation. The morphological characterization of the crystallizable materials was done by polarized optical microscopy that provided also evidence of homogeneity/phase separation. Additionally, the rheological and thermodynamic properties of the NADES and the effect of water content were also studied. The results show these systems have Newtonian behavior and present significant viscosity decrease with temperature and water content, due to increase on the molecular mobility. The anhydrous systems present viscosities that range from higher than 1000Pa.s at 20°C to less than 1Pa.s at 70°C. DSC characterization confirms that for water content as high as 1:1:1 molar ratio, the mixture retains its single phase behavior. The results obtained demonstrate that the NADES properties can be finely tunned by careful selection of its constituents. NADES present the necessary properties for use as extraction solvents. They can be prepared from inexpensive raw materials and tailored for the selective extraction of target molecules. The data produced in this work is hereafter importance for the selection of the most promising candidates avoiding a time consuming and expensive trial and error phase providing also data for the development of models able to predict their properties and the mechanisms that allow the formation of the deep eutectic mixtures.

Optimization of low-cost nutritional supplementation for lignocellulosic ethanol fermentation

[Excerpt] Bioethanol from lignocellulosic materials (LCM), also called second generation bioethanol, is considered a promising alternative to first generation bioethanol. An efficient production process of lignocellulosic bioethanol involves an effective pretreatment of LCM to improve the accessibility of cellulose and thus enhance the enzymatic saccharification. One interesting approach is to use the whole slurry from treatment, since allows economical and industrial benefits: washing steps are avoided, water consumption is lower and the sugars from liquid phase can be used, increasing ethanol concentration [1]. However, during the pretreatment step some compounds (such as furans, phenolic compounds and weak acids) are produced. These compounds have an inhibitory effect on the microorganisms used for hydrolysate fermentation [2]. To overcome this, the use of a robust industrial strain together with agro-industrial by-products as nutritional supplementation was proposed to increase the ethanol productivities and yields. (...)

Why do we need randomized and epidemiological studies on cardiovascular disease? Evidence-based cardiology VII

Over the last two decades the results of randomized clinical studies, which are powerful aids for correctly assessing therapeutical strategies, have consolidated cardiological practice. In addition, scientifically interesting hypotheses have been generated through the results of epidemiological studies. Properly conducted randomized studies without systematic errors and with statistical power adequate for demonstrating moderate and reasonable benefits in relevant clinical outcomes have provided reliable and strong results altering clinical practice, thus providing adequate treatment for patients with cardiovascular disease (CVD). The dissemination and use of evidence-based medicine in treating coronary artery disease (CAD), heart failure (HF), and in prevention will prevent hundreds of thousands of deaths annually in developed and developing countries. CVD is responsible for approximately 12 million deaths annually throughout the world, and approximately 60% of these deaths occur in developing countries. During recent years, an increase in mortality and morbidity rates due to CVD has occurred in developing countries. This increase is an indication that an epidemiological (demographic, economical, and health-related) transition is taking place in developing countries and this transition implies a global epidemic of CVD, which will require wide-ranging and globally effective strategies for prevention. The identification of conventional and emerging risk factors for CVD, as well as their management in high-risk individuals, has contributed to the decrease in the mortality rate due to CVD. Through a national collaboration, several multi-center and multinational randomized and epidemiological studies have been carried out throughout Brazil, thus contributing not only to a generalized scientific growth in different Brazilian hospitals but also to the consolidation of an increasingly evidence-based clinical practice.

Production and extraction of polysaccharides and oligosaccharides and their use as new food additives

Polysaccharides and oligosaccharides can improve quality and enhance nutritional value of final food products due to their technological and nutritional features ranging from their capacity to improve texture to their effect as dietary fibers. For this reason, they are among the most studied ingredients in the food industry. The use of natural polysaccharides and oligosaccharides as food additives has been a reality since the food industry understood their potential technological and nutritional applications. Currently, the replacement of traditional ingredients and/or the synergy between traditional ingredients and polysaccharides and oligosaccharides are perceived as promising approaches by the food industry. Traditionally, polysaccharides have been used as thickening, emulsifying, and stabilizing agents, however, at this moment polysaccharides and oligosaccharides claim health and nutritional advantages, thus opening a new market of nutritional and functional foods. Indeed, their use as nutritional food ingredients enabled the food industry to develop a countless number of applications, e.g., fat replacers, prebiotics, dietary fiber, and antiulcer agents. Based on this, among the scientific community and food industry, in the last years many research studies and commercial products showed the possibility of using either new or already used sources (though with changed properties) of polysaccharides for the production of food additives with new and enhanced properties. The increasing interest in such products is clearly illustrated by the market figures and consumption trends. As an example, the sole market of hydrocolloids is estimated to reach $7 billion in 2018. Moreover, oligosaccharides can be found in more than 500 food products resulting in a significant daily consumption. A recent study from the Transparency Market Research on Prebiotic Ingredients Market reported that prebiotics' demand was worth $2.3 billion in 2012 and it is estimated to reach $4.5 billion in 2018, growing at a compound annual growth rate of 11.4% between 2012 and 2018. The entrance of this new generation of food additives in the market, often claiming health and nutritional benefits, imposes an impartial analysis by the legal authorities regarding the accomplishment of requirements that have been established for introducing novel ingredients/food, including new poly- and oligosaccharides. This chapter deals with the potential use of polysaccharides and oligosaccharides as food additives, as well as alternative sources of these compounds and their possible applications in food products. Moreover, the regulation process to introduce novel polysaccharides and oligosaccharides in the market as food additives and to assign them health claims is discussed.

Reactivity studies on chromene derivatives

Dissertação de mestrado em Medicinal Chemistry