Efeitos in vivo e in vitro de agonistas parciais do receptor NOP: implicações para o tratamento da ansiedade, depressão e mania

Introduction: This study aimed to investigate the effects of the two peptide NOP partial agonists (UFP-113 and [F/G]N/OFQ(1-13)NH2) and the non peptide NOP partial agonist (AT-090) in the mouse emotional behavior as well as in the intracellular transduction pathways following the receptor binding. Methods: Male Swiss or CD-1 mice were used in this study together with NOP(+/+) and NOP(-/-) mice. The elevated plus maze (EPM) was used to evaluate the effects of compounds on anxiety-like behaviors. Diazepam and the NOP agonists, N/OFQ and Ro 65-6570, were used as positive controls in the EPM. NOP(+/+) and NOP(-/-) mice were used to evaluate the selectivity of those compounds that induced anxiolytic-like behaviors. The forced swim test (FST) was used to evaluate the effects of compounds on depressive-like behaviors. Nortriptyline and the NOP antagonists, UFP-101 and SB-612111, were used as positive controls in the FST. The effects of N/OFQ, UFP-101, SB-612111, UFP-113, [F/G]N/OFQ(1-13)NH2, and AT-090 were assessed in the methylphenidate-induced hyperlocomotion (MIH) test; in this assay valproate was used as positive control. The G protein and β-arrestin 2 transduction pathways of NOP receptor agonists (N/OFQ and Ro 65-6570), antagonist (UFP-101), and partial agonists (UFP-113, [F/G]N/OFQ(1-13)NH2, and AT-090) were also evaluated using an innovative assay that measures a bioluminescence resonance energy transfer process. For this, cell lines permanently co-expressing the NOP receptor coupled to luciferase (energy donor), and green fluorescent protein (energy acceptor) coupled to one of the effector proteins (G protein or β-arrestin 2) were used. Results: Diazepam (1 mg/kg), N/OFQ (1 nmol), Ro 65-6570 (0.1 mg/kg), and AT-090 (0.01 mg/kg) induced anxiolytic-like effect in mice in the EPM. The effects of Ro 65-6570 and AT-090 were selective to NOP receptor. UFP-113 (0.01-1 nmol) and [F/G]N/OFQ(1-13)NH2 (0.1-3 nmol) were inactive in the EPM. In the FST, nortriptyline (30 mg/kg), UFP-101 (10 nmol), SB-612111 (10 mg/kg), UFP-113 (0.01 and 0.1 nmol), and [F/G]N/OFQ(1-13)NH2 (0.3 and 1 nmol) induced antidepressant-like effects, while AT-090 (0.001-0.1 mg/kg) was inactive in this assay. The effects of UFP-113 and [F/G]N/OFQ(1-13)NH2 were selective to NOP receptor. Valproate (400 mg/kg) counteracted methylphenidate (MPH, 10 mg/kg)-induced hyperlocomotion in mice in the open field. N/OFQ (1 nmol), UFP-113 (0.01-0.1 nmol), and [F/G]N/OFQ(1-13)NH2 (1 nmol) were also able to reduce the MPH-induced hyperlocomotion, without changing the locomotor activity per se. The effect of UFP-113 was selective to NOP receptor. The UFP-101 (10 nmol), SB-612111 (10 mg/kg), and AT-090 (0.001-0.03 mg/kg) did not change the hyperlocomotor effect of methylphenidate. In vitro, N/OFQ and Ro 65-6570 behaved as NOP full agonists for G-protein and β-arrestin 2 pathways. AT-090 behaved as NOP receptor partial agonist for both transduction pathways, while UFP-113 and [F/G]N/OFQ(1-13)NH2 behaved as partial agonists and antagonists of NOP receptor for NOP/G protein and NOP/β-arrestin 2, respectively. UFP-101 behaved as NOP receptor antagonist for both transduction pathways. Conclusion: NOP ligands producing same effects on NOP/G protein interaction (partial agonism), but with opposite effects on β-arrestin 2 recruitment (partial agonism vs antagonism), can promote different in vivo effects on anxiety and mood as it was observed in the behavioral tests. This work corroborates the potential of NOP receptor as an innovative pharmacological target for the treatment of emotional disorders.

Mudança dos processos de negócios e adequação da TI nas empresas em decorrência da implantação do sistema público de escrituração digital SPED: um estudo de casos múltiplos

Companies have always been organized by processes, often imperceptible to its employees. With the advancement of technology, organizational processes currently run an organization through computers, and thus generate immediate information that is available to each sector. With the objective of seeking business information in real time, the government created the SPED - Public System of Digital, which involves three subsystems, which are the Electronic Invoice, Digital Accounting Bookkeeping and Digital Tax Bookkeeping. This system is revolutionizing the business structures when gathering, in an innovative way, all information and interlinked business processes. For the implementation of SPED, a revision in the organizational processes is required, since the information is generated and is sent online to the government, without mistakes. Thus the study aimed to analyze the change brought about by the implementation of the Public System of Digital SPED in the main business processes. In order to do so, we have performed a multiple case study involving three companies in the state of Para, two operate in wholesale and one explores agribusiness. The Data collection was performed by accounting professionals, IT and managers. According to the results obtained, it was found that in two companies, the IT infrastructure was capable of deploying the new system without major problems, while one company had more difficulties to cope with the new system. However, all companies had to examine its processes to make the customizations needed to fit. It was also observed that there is no IT Governance in two companies. Therefore, we recommend the use of an appropriate model, not only for the implementation of SPED, but as a way to manage and extract better results from investment in information technology

Práticas interdisciplinares no ensino superior: a experiência do curso de graduação em administração da UNAMA - Pará

This work addresses the study of interdisciplinarity in higher administration education, a topic of great relevance in the present context, due to guidelines issued by Ministry of Education through the National Curriculum Guidelines -NCGs for undergraduate courses in Management. The attention on the subject emerges from the gained experience of a researcher and teacher working as manager of an undergraduate course in Business Administration who set up interdisciplinarity through interdisciplinary projects in a management course pedagogical project at a private university in State of Pará/Brazil. The work rebuilds and reports experiences, and studies the practice of lecturers involved in those interdisciplinary actions. The study aimed to identify changes in pedagogical practices of teachers involved in the searched interdisciplinary experience. To address the questions that directed the work and achieve proposed objectives, from a qualitative approach, a significant bibliographical and documentary work was conducted on the topic. In the survey carried out on secondary sources such as publications of major authors and scientific papers reporting interdisciplinary experiences in higher administration education, it was found that interdisciplinarity for its ambiguous character is still poorly understood by teachers, and reports on its application in administration teaching are incipient. This study also used data collected from primary sources, from dialogues through interviews with educational fellows - teachers and officers of the institution that served as locus of the research, who had the opportunity to experience the studied interdisciplinary experience. Data were processed and analyzed using content analysis technique. Research results showed that teachers of the institution of research have a good understanding of meaning of interdisciplinarity as a link between disciplines; it was also found substantial evidence of changes in teaching practices and actions of such teachers based on their participation in interdisciplinary projects. Although the experience studied can be considered innovative and challenging, much needs to be done in the course management for achievement of interdisciplinary actions in the course, particularly regarding to the removal of institutional, methodological, psychosocial, epistemological obstacles in operationalizing interdisciplinary practices, with emphasis on the need of a process of continuous and specific training aiming at developing skills for interdisciplinary acting, to the extent that these education professionals do not perceive themselves able to act as interdisciplinary lecturers

Avaliação ambiental de manguezais adjacentes aos campos petrolíferos de Macau e Serra (RN), como subsídio às medidas mitigadoras ao processo erosivo

Among the various effects caused by the climate change and human intervention, the mangrove ecosystem changes through of the years has been worth mentioning, which hasn t known which are the pros and cons for the adjacent coastal and estuarine environments yet. It happens due to the present dynamism in these areas, besides of the difficult understanding of the processes associated with evolution. This study aimed to environmentally evaluate adjacent mangroves from the Macau and Serra oil fields, located on Rio Grande do Norte northern coast, to support the mitigating actions related to the containment of the erosive process, as well as, according to the principles of the Clean Development Mechanism (CDM), to assess the amount of atmospheric carbon sequestered by the studied ecosystem. An inventory was conducted through mangrouve mapping which has supplied this research, especially regarding to the structural characterization of mangrove areas. To understand the local mangrove behavior in a greater level detail, techniques of remote sensing, GIS and GPS were used to make an analogy between the current and past states of the mangrove studied, allowing to make anticipated projections for the future impacts or changes in that region. This study combined data from multispectral LANDSAT 5 TM, Landsat 7 ETM+ with radar microwave data from SAR RADARSAT-1, which increased the interpretation capacity of the data from optical sensor systems. The interpretations have been supported by the data field, representing a better and innovative methodology for the environmental and taxonomic characterization of mangrove forests considered. The results reveal that mangroves of the Ponta do Tubarão Sustainable Development Reserve are biologically representative areas and providing a variety of benefits, especially for local communities, constituting the priority sites for actions development aimed at conservation. They also have been showing the necessity to make mitigating measures in order to recover degraded areas through reforestation or creating new areas of mangrove, as currently 7.1% of the mangrove forests studied are dead or in an advanced state of decomposition. The amount of atmospheric carbon sequestered proved very significant when analyzed for the whole area, which is able to sequester atmospheric 4,294,458 Ton CO2 per year

Obtenção de álcool alílico (PROP-2-EN-1-OL) a partir da glicerina derivada do biodiesel de óleo de mamona

In this work, biodiesel was produced from castor oil that was a byproduct glycerin. The molar ratio between oil and alcohol, as well as the use of (KOH) catalyst to provide the chemical reaction is based on literature. The best results were obtained using 1 mol of castor oil (260g) to 3 moles of methyl alcohol (138g), using 1.0% KOH as catalyst at a temperature of 260 ° C and shaken at 120 rpm. The oil used was commercially available, the process involves the reaction of transesterification of a vegetable oil with methyl alcohol. The product of this reaction is an ester, biodiesel being the main product and the glycerin by-product which has undergone treatment for use as raw material for the production of allyl alcohol. The great advantage of the use of glycerin to obtain allyl alcohol is that its use eliminates the large amount of waste of the biodiesel and various forms of insult to the environment. The reactions for the formation of allyl alcohol was conducted from formic acid and glycerin in a ratio 1/1, at a temperature of 260oC in a heater blanket, being sprayed by a spiral condenser for a period of 2 hours and the product obtained contains mostly the allylic alcohol .. The monitoring of reactions was performed by UV-Visible Spectrophotometer: FTIR Fourier transform, the analysis showed that these changes occur spectrometer indicating the formation of the product allylic alcohol (prop-2-en-1-ol) in the presence of water, This alcohol was appointed Alcohol GL. The absorption bands confirms that the reaction was observed in (υ C = C) 1470 -1600 cm -1 and (υ CO), 3610-3670 attributed to C = C groups and OH respectively. The thermal analysis was carried out in a thermogravimetric analyzer SDT Q600, where the mass and temperature are displayed against time, that allows checking the approximate rate of heating. The innovative methodology developed in the laboratory (LABTAM, UFRN), was able to treat the glycerine produced by transesterification of castor oil and used as raw material for production of allyl alcohol, with a yield of 80%, of alcohol, the same is of great importance in the manufacture of polymers, pharmaceuticals, organic compounds, herbicides, pesticides and other chemicals