DISCLOSURE DE ATIVOS E PASSIVOS CONTIGENTES NAS EMPRESAS INTEGRANTES DO ÍNDICE IBRX100 DA BM&FBOVESPA

O Disclosure tem por objetivo esclarecer informações contábeis que subsidiem os investidores no processo de tomada de decisões, buscando sua autenticidade e opinando sobre as causas. Estas informações podem ser evidenciadas por meio das demonstrações financeiras, notas explicativas e outros relatórios disponibilizados pelas organizações. Desta forma, este estudo objetivou identificar os níveis de evidenciação das informações contábeis acerca de provisões, ativos e passivos contingentes, divulgadas pelas empresas integrantes do IBrX100. Foi realizada uma pesquisa documental, com informações extraídas do banco de dados da Economática e do site da BM&FBovespa, utilizando as empresas listadas na IBrX100 entre os anos de 2014 a 2016. Os resultados revelam que o segmento do Novo Mercado, composto por 54 corporações, apresenta a maior média nos níveis de evidenciação. O segmento com menor quantidade de empresas vinculadas foi o tradicional, com 05 empresas. Os setores de atuação com maior nível de representatividade, com 14 empresas descritas, são Consumo Cíclico, Financeiro e Utilidade Pública, correspondendo a 51,90% das empresas listadas. E as empresas com menor nível de representatividade são as empresas de Móveis, contando apenas com 1 empresa, que corresponde a 1,2% do total de empresas listadas. Ao final, são apresentadas limitações e sugestões para novas pesquisas

Accelerating drug discovery for Alzheimer's disease: best practices for preclinical animal studies

Animal models have contributed significantly to our understanding of the underlying biological mechanisms of Alzheimer's disease (AD). As a result, over 300 interventions have been investigated and reported to mitigate pathological phenotypes or improve behavior in AD animal models or both. To date, however, very few of these findings have resulted in target validation in humans or successful translation to disease-modifying therapies. Challenges in translating preclinical studies to clinical trials include the inability of animal models to recapitulate the human disease, variations in breeding and colony maintenance, lack of standards in design, conduct and analysis of animal trials, and publication bias due to under-reporting of negative results in the scientific literature. The quality of animal model research on novel therapeutics can be improved by bringing the rigor of human clinical trials to animal studies. Research communities in several disease areas have developed recommendations for the conduct and reporting of preclinical studies in order to increase their validity, reproducibility, and predictive value. To address these issues in the AD community, the Alzheimer's Drug Discovery Foundation partnered with Charles River Discovery Services (Morrisville, NC, USA) and Cerebricon Ltd. (Kuopio, Finland) to convene an expert advisory panel of academic, industry, and government scientists to make recommendations on best practices for animal studies testing investigational AD therapies. The panel produced recommendations regarding the measurement, analysis, and reporting of relevant AD targets, th choice of animal model, quality control measures for breeding and colony maintenance, and preclinical animal study design. Major considerations to incorporate into preclinical study design include a priori hypotheses, pharmacokinetics-pharmacodynamics studies prior to proof-of-concept testing, biomarker measurements, sample size determination, and power analysis. The panel also recommended distinguishing between pilot 'exploratory' animal studies and more extensive 'therapeutic' studies to guide interpretation. Finally, the panel proposed infrastructure and resource development, such as the establishment of a public data repository in which both positive animal studies and negative ones could be reported. By promoting best practices, these recommendations can improve the methodological quality and predictive value of AD animal studies and make the translation to human clinical trials more efficient and reliable

Fed-Batch Production of Saccharomyces cerevisiae L-Asparaginase II by Recombinant Pichia pastoris MUTs Strain

L-Asparaginase (ASNase) is used in the treatment of acute lymphoblastic leukemia, being produced and commercialized only from bacterial sources. Alternative Saccharomyces cerevisiae ASNase II coded by the ASP3 gene was biosynthesized by recombinant Pichia pastoris MUTs under the control of the AOX1 promoter, using different cultivation strategies. In particular, we applied multistage fed-batch cultivation divided in four distinct phases to produce ASNase II and determine the fermentation parameters, namely specific growth rate, biomass yield, and enzyme activity. Cultivation of recombinant P. pastoris under favorable conditions in a modified defined medium ensured a dry biomass concentration of 31 gdcw.L−1 during glycerol batch phase, corresponding to a biomass yield of 0.77 gdcw.gglycerol-1 and a specific growth rate of 0.21 h−1. After 12 h of glycerol feeding under limiting conditions, cell concentration achieved 65 gdcw.L−1 while ethanol concentration was very low. During the phase of methanol induction, biomass concentration achieved 91 gdcw.L−1, periplasmic specific enzyme activity 37.1 U.gdcw-1, volumetric enzyme activity 3,315 U.L−1, overall enzyme volumetric productivity 31 U.L−1.h−1, while the specific growth rate fell to 0.039 h−1. Our results showed that the best strategy employed for the ASNase II production was using glycerol fed-batch phase with pseudo exponential feeding plus induction with continuous methanol feeding

Multifunctional, self-assembling, anionic peptide-lipid nanocomplexes for targeted siRNA delivery

Formulations of cationic liposomes and polymers readily self-assemble by electrostatic interactions with siRNA to form cationic nanoparticles which achieve efficient transfection and silencing in vitro. However, the utility of cationic formulations in vivo is limited due to rapid clearance from the circulation, due to their association with serum proteins, as well as systemic and cellular toxicity. These problems may be overcome with anionic formulations but they provide challenges of self-assembly and transfection efficiency. We have developed anionic, siRNA nanocomplexes utilizing anionic PEGylated liposomes and cationic targeting peptides that overcome these problems. Biophysical measurements indicated that at optimal ratios of components, anionic PEGylated nanocomplexes formed spherical particles and that, unlike cationic nanocomplexes, were resistant to aggregation in the presence of serum, and achieved significant gene silencing although their non-PEGylated anionic counterparts were less efficient. We have evaluated the utility of anionic nanoparticles for the treatment of neuronal diseases by administration to rat brains of siRNA to BACE1, a key enzyme involved in the formation of amyloid plaques. Silencing of BACE1 was achieved in vivo following a single injection of anionic nanoparticles by convection enhanced delivery and specificity of RNA interference verified by 5' RACE-PCR and Western blot analysis of protein

DISCLOSURE DE ATIVOS E PASSIVOS CONTIGENTES NAS EMPRESAS INTEGRANTES DO ÍNDICE IBRX100 DA BM&FBOVESPA

O Disclosure tem por objetivo esclarecer informações contábeis que subsidiem os investidores no processo de tomada de decisões, buscando sua autenticidade e opinando sobre as causas. Estas informações podem ser evidenciadas por meio das demonstrações financeiras, notas explicativas e outros relatórios disponibilizados pelas organizações. Desta forma, este estudo objetivou identificar os níveis de evidenciação das informações contábeis acerca de provisões, ativos e passivos contingentes, divulgadas pelas empresas integrantes do IBrX100. Foi realizada uma pesquisa documental, com informações extraídas do banco de dados da Economática e do site da BM&FBovespa, utilizando as empresas listadas na IBrX100 entre os anos de 2014 a 2016. Os resultados revelam que o segmento do Novo Mercado, composto por 54 corporações, apresenta a maior média nos níveis de evidenciação. O segmento com menor quantidade de empresas vinculadas foi o tradicional, com 05 empresas. Os setores de atuação com maior nível de representatividade, com 14 empresas descritas, são Consumo Cíclico, Financeiro e Utilidade Pública, correspondendo a 51,90% das empresas listadas. E as empresas com menor nível de representatividade são as empresas de Móveis, contando apenas com 1 empresa, que corresponde a 1,2% do total de empresas listadas. Ao final, são apresentadas limitações e sugestões para novas pesquisas

Hypoxia-induced microRNA-424 expression in human endothelial cells regulates HIF-α isoforms and promotes angiogenesis

Adaptive changes to oxygen availability are critical for cell survival and tissue homeostasis. Prolonged oxygen deprivation due to reduced blood flow to cardiac or peripheral tissues can lead to myocardial infarction and peripheral vascular disease, respectively. Mammalian cells respond to hypoxia by modulating oxygen-sensing transducers that stabilize the transcription factor hypoxia-inducible factor 1α (HIF-1α), which transactivates genes governing angiogenesis and metabolic pathways. Oxygen-dependent changes in HIF-1α levels are regulated by proline hydroxylation and proteasomal degradation. Here we provide evidence for what we believe is a novel mechanism regulating HIF-1α levels in isolated human ECs during hypoxia. Hypoxia differentially increased microRNA-424 (miR-424) levels in ECs. miR-424 targeted cullin 2 (CUL2), a scaffolding protein critical to the assembly of the ubiquitin ligase system, thereby stabilizing HIF-α isoforms. Hypoxia-induced miR-424 was regulated by PU.1-dependent transactivation. PU.1 levels were increased in hypoxic endothelium by RUNX-1 and C/EBPα. Furthermore, miR-424 promoted angiogenesis in vitro and in mice, which was blocked by a specific morpholino. The rodent homolog of human miR-424, mu-miR-322, was significantly upregulated in parallel with HIF-1α in experimental models of ischemia. These results suggest that miR-322/424 plays an important physiological role in post-ischemic vascular remodeling and angiogenesis