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.

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.

Effect of trypsin inhibitor from Crotalaria pallida seeds on Callosobruchus maculatus (cowpea weevil) and Ceratitis capitata (fruit fly)

GOMES, Carlos E. M. et al. Effect of trypsin inhibitor from Crotalaria pallida seeds on Callosobruchus maculatus (cowpea weevil) and Ceratitis capitata (fruit fly). Plant Physiology and Biochemistry (Paris), v. 43, n. 12, p. 1095-1102, 2005.ISSN 0981-9428. DOI:10.1016/j.plaphy.2005.11.004.

De repente, tudo mudou de lugar: refletindo sobre metamorfose urbana e gentrificação em Mossoró-RN

This study aims at solidifying the theoretical bases to provide, above all, an explanation for this phenomenon which currently happens, with a scenario of social, political, economic and cultural transformations worldwide in medium cities. Nevertheless, because it has different dimensions from its transformation axes, gentrification comes with change, but also with the introduction of a new purpose in the space using and occupation, outlining in this context the identity of places from the formation of centralities with the presence of flows with social and economic dynamicsThe current forms of geographic space appropriation show the directions of the senses and ideological profile which recreates the meanings and uses of content and materials from descriptions of a historical past. However, today there is an economic context in the urban space which refers to a search of strategies for change, i.e., the acquisition of parameter aimed at meeting the demands of the relationship between capital and labor, which ends up overriding some actions for the specification of the transformation methods within the urban space to be explained by new needs and also by the agents from the value adding to their interests and investments. Thus, we assume that the appreciation/gentrification of urban spaces may or may not result from the building of a public space, since the dialogic structure as a place of political interaction externalize conflicts and disagreements in general; it keeps segregating spaces. As new spaces are transformed, the access to them tends to happen with particular restriction, whereas some places like parks, shopping malls, high-rise and horizontal condos are the scene for major professional and family events. In this context, the gentrification process is used to designate interventions in the urban environment, in certain city spaces which are considered central to public and private investments. A historical place is permitted to be presented as a scenario, a stage full of attractions, through the transformation process. Studying gentrification consists of an analysis of the underlying interests in the transformation of these areas, and especially of the assessment of the interest level in the private sector to partner in order to modify the landscape. Gentrification results from the transformation processes of capital, which influences the efforts and investments application in order to establish and achieve optimal economic growth, focusing on a location socio-culturally centered in the urban space. Thus, the urban social structure develops in the light of some questions that relate not only the cities growth but also environmental conditions it provides in cities like Mossoro, State of Rio Grande do Norte, Brazil 2005 a 2011.

Atividade bioinseticida e mecanismo de ação de vicilinas de sementes Erythrina velutina sobre moscas-das frutas Ceratitis capitata

The fruit fly Ceratitis capitata is considered the most destructive pest of the world fruitculture. Many pest management practices, mainly based on agrochemicals, have been developed to allow the world-wide commerce of fruit. Solutions to decrease the use of synthetic insecticides in agriculture are based on the development of new target-specific compounds which cause less damage to the environment, especially vegetal proteins with insecticidal effects. The aim of this work was to evaluate the deleterious effect of a purified vicilin of E. velutina (EvV) seeds to C. capitata larvae and adult insects and to investigate the mechanisms involved in these effects. EvV was purified, characterized and its deleterious effect was tested in bioassay systems. EvV mechanism of action was determined by immunodetection techniques and fluorescence localization in chitin structures that are present in C. capitata digestory system. EvV is a glycoprotein with affinity to chitin. Its molecular weight, of 216,57 kDa, was determined by gel filtration chromatography in FPLC system. Using SDS-PAGE, it was possible to observe EvV dissociation in two main subunits of 54,8 and 50,8 kDa. When it was submitted to eletrophoresis in native conditions, EvV presented only one band of acid characteristic. The WD50 and LD50 values found in the bioassays were 0,13% and 0,14% (w/w), respectively for the larvae. EvV deleterious effects were related to the binding to chitin structures presented in peritrophic membrane and gut epithelial cells, associated with its low digestibility in C. capitata digestive tract. The results described herein are the first demonstration of the larvicidal effects of plant protein on C. capitata larvae. EvV may be part of the pest management programs, in the toxic bait composition, or an alternative in plant improvement program

Interação de microorganismos na solubilização de fósforo e potássio de rochas para produção de biofertilizantes

he present model of agriculture is based on intensive use of industrial inputs, due to its rapid response, but it brings harmful consequences to the environment, and it is necessary the use of modern inputs. And an alternative is the use of rock biofertilizers in agriculture, a product easy to use, with higher residual effect and does not harm the environment. The objective of study was to evaluate the inoculation and co-inoculation of different microorganisms in the solubilization of rock phosphate and potash ground microbial evaluating the best performance in the production of biofertilizers comparing with rocks pure in soil chemical properties and, verify effect of inoculation of the bacterium Paenibacillus polymyxa in the absorption of minerals dissolved in the development of cowpea (Vigna unguiculata [L.] Walp.). The first bioassay was conducted in Laboratory (UFRN) for 72 days in Petri dishes, where the rock powder was increased by 10% and sulfur co-inoculated and inoculated with bacterial suspension of Paenibacillus polymyxa grown in medium tryptone soy broth, Ralstonia solanacearum in medium Kelman, Cromobacterium violaceum in medium Luria-Bertani and Acidithiobacillus thiooxidans in medium Tuovinen and Kelly,and fungi Trichoderma humatum and Penicillium fellutanum in malt extract. Every 12 days, samples were removed in order to build up the release curve of minerals. The second bioassay was conducted in a greenhouse of the Agricultural Research Corporation of Rio Grande do Norte in experimental delineation in randomized block designs, was used 10 kg of an Yellow Argissolo Dystrophic per pot with the addition of treatments super phosphate simple (SS), potassium chloride (KCl), pure rock, biofertilizers in doses 40, 70, 100 and 200% of the recommendation for SS and KCl, and a control, or not inoculated with bacteria P. polymyxa. Were used seeds of cowpea BRS Potiguar and co-inoculated with the bacterial suspension of Bradyrhizobium japonicum and P. polymyxa. The first crop was harvested 45 days after planting, were evaluated in the dry matter (ADM), macronutrients (N, P, K, Ca, Mg) and micronutrients (Zn, Fe, Mn) in ADM. And the second at 75 days assessing levels of macro end micronutrients in plants and soil, and the maximum adsorption capacity of P in soil. The results showed synergism in co-inoculations with P. polymyxa+R. solanacearum and, P. polymyxa+C. violaceum solubilizations providing higher P and K, respectively, and better solubilization time at 36 days. The pH was lower in biofertilizers higher doses, but there was better with their addition to P at the highest dose. Significant reduction of maximum adsorption capacity of phosphorus with increasing dose of biofertilizer. For K and Ca was better with SS+KCl, and Mg to pure rock. There was an effect of fertilization on the absorption, with better results for P, K and ADM with SS+KCL, and N, Ca and Mg for biofertilizers. Generally, the P. polymyxa not influence the absorption of the elements in the plant. In treatments with the uninoculated P. polymyxa chemical fertilizer had an average significantly higher for weight and number of grains. And in the presence of the bacteria, biofertilizers and chemical fertilizers had positive values in relation to rock and control. The data show that the rocks and biofertilizers could meet the need of nutrients the plants revealed as potential for sustainable agriculture

Atividades educativas aos portadores de periodontite crônica: escuta e troca de saberes no autocuidado em saúde bucal

This research aimed at evaluating oral health education activities for Periodontitis carriers, emphasizing the motivation for self-care and understanding the cultural aspects involved. This was a qualitative and quantitative study. Based on the qualitative referential, 20 interviews were done, in which differences between scientific and popular explicative models of the health-illness process were verified, besides the increased knowledge and motivation in relation to the use of preventive measures and also the fails in the understanding of the chronic character of periodontitis, enhancing frustration and guilty feelings in the patients. Two groups were structured: intervention and control. The intervention group was submitted to clinical attendance and education activities, while the control group undergone the traditional clinical attendance only. The sample consisted of 51 participants of intervention group and 47 of control group. Structured interviews were conducted at the beginning and at the end of the treatment in order to evaluate the knowledge and motivation for self-care in both groups. For comparison between the previous and post moments in both groups, there were applied McNemar tests with a probability of p < 0.05. In intervention group there was an increase in knowledge related to the name, the causes and related factors of the disease (p < 0.05). In control group there wasn t a rise in the understanding of the diseases chronic character, unlike in intervention group. However, in what concerns self-care, a greatest frequency in medium and high scores was observed in both groups. By this study, it is conclude that there is a common sense knowledge about the importance of preventive techniques and poor oral health as causing periodontitis; clinical interventions for bearers of chronic Periodontitis do not add values to the patients, regarding the illness, its causes and its chronic character; popular beliefs stay in their imagination, and the patients have a increased motivational capacity for self-care

A evolução do emprego formal industrial nas cidades médias do estado do Ceará (Juazeiro do Norte, Crato e Sobral) no período de 1990 a 2010

The work consists in a discussion of the evolution of formal employment in the industrial cities of Ceará state averages from 1990 to 2010, since this period was marked by important changes. It is emphasized that in order to achieve this aim, the present study was based on a survey of relevant literature on the subject, as well as the use of the Annual Report of Social Information (RAIS), published by the Ministry of Labour and Employment (MTE) and the Brazilian Institute of Geography and Statistics (IBGE). The central question to be considered in this study is how we evolved formal employment industry in medium-sized cities (Juazeiro do Norte, Crato and Sobral) of Ceará? The assumption that guides this work is that given the economic policies of the 1990 and 2000 these policies encouraged the relocation, thus implying significant growth in the formal manufacturing employment in these cities. Regarding the results obtained in the survey, it was found that the industrial sector of these cities, showed considerable dynamism in what refers to the expansion of establishments. When observed in percentage terms medium-sized cities (345.5%) had the highest growth in number of establishments in the 1990s with rates higher than the Northeast region (285.9%) and Brazil (167.5%). The highlight was the city of Juazeiro, with the highest concentration of micro and small footwear companies in the state. Regarding the number of formal jobs created in medium-sized cities, it went from 6.596 in 1990 to 41.660 million formal jobs in 2010, with a growth rate of 532%. The sector contributed most to employment generation was the footwear. Although the levels of minimum wages, the 1990 recorded the lowest levels. In the 2000, there were real gains in levels of minimum wages in all cities, however, it may be noted that over the decades there has been significant momentum. However, this momentum was not enough to prevent the end of the study period CMs-Ceará present low wages

Corpo e saúde: reflexões sobre o quadro "Medida Certa"

The present scenario is permeated by different comprehensions about the body and health. These are the result of a historical process experienced by men in different times and social contexts through which were being built. Faced this scenario, we emphasize the media as a powerful means of information and training ideas regarding the body and health of theses. The media also as a means of mediating information we present characteristics of the social scenario where is inserted. In our research we bring reflects about the comprehensions, knowledge and practices propagated by the way the body and health under "Medida Certa" of the program Fantastico the broadcaster Globo Telecommunications, in order to identify how Physical Education, has contributed the construction of knowledge disseminated. Therefore, we focus our analysis to the table "Medida Certa" exhibited by Fantastico in the months of April, May and June of 2011.The data for analysis were collected through the videos shown live in Fantastic and the information provided in the blog that table. Thus, we had 14 videos shown live, 16 videos posted on the blog, 97 posts in blog. As technique of analysis of the datas used of content analysis of the Bardin (2011). About body obtained as analytical categories: body as operating system; biological body; fragmented body exterior to the subject; body trailer quantified to patterns; subject body. How to health we analyze the categories of health existential: health existential based in biological indices of normality; health existential associated with weight loss and aesthetic patterns; health existential associated with physical activity and nutritional control; and finally we propose a comprehension of health existential. Therefore, from the analysis of the data evidenced a predominance of comprehensions, knowledge and practices about the body and health guided the biological constituents of the body, quantification and classification in medium and normal patterns on pervasive forms of care, in the linear association among physical activity and nutritional control with health, evidenced that Physical Education has contributed to these constructions, through some of his discourses with emphasis on biological aspects. Thus, in our study we advocate an understanding of not only the body as object, but also as a subject clipped by organic, cultural, historical and social elements, a living body, feeling, desire and above all expresses itself, and health viewed as something body, interlaced through the biological, cultural, historical and emotional aspects of this body that coexist in this society

Aplicação da metodologia seis sigma em uma empresa de médio porte do setor têxtil

The Six Sigma methodology has received considerable attention in the last two decades. This is due to its great potencial to reduce processes variability, through the use of accurate data, facts and statistical techniques. The methodology seeks to improve the quality of products and services, maximizing the company s financial performance. Specifically, its implementation and results in medium-sized textile enterprises is unknow, although there are signs that the methodology can be applied with success. Considering this scenario, the goal of this research is to describe the application of the Six Sigma methodology in a médium-sized textile company specialized in the production of male shirts in the satate of Rio Grande do Norte, Brazil. First, we present a literature review, seeking to highlight the themes of quality, Six Sigma and its methodology for improvement. Then, we show the implementation of the project selected, depicting the steps and procedures that must be performed. The results confirm the efficiency of Six Sigma in providing significant gains to companies. It is observed substantial improvements in the speed of product development and the flexibility of the parts produced, reducing the process lead time from 12.5 to 6.2 days, which means a performance improvement of over 50%. This leads also to cultural and behaviour change, creating motivation for implementation of new projects and a continuous search for knowledge

Desenvolvimento de um Sistema de Automação e Supervisão de Máquinas Dispensadoras Através da Internet

This paper aims to design and develop a control and monitoring system of vending machines, based on a Central Processing Unit with peripheral Internet communication. Coupled with the condom vending machines, a data acquisition module will be connected to the original circuits in order to collect and send, via internet, the information to the healthy government agencies, in the form of charts and reports. In the face of this, such agencies may analyze these data and compare them with the rates of reduction, in medium or long term, of the STD/AIDS in their respective regions, after the implementation of these vending machines, together with the conventional preventing programs. Reading the methodology, this paper is about an explaining and bibliography research, with the aspect of a qualitative-quantitative methodology, presenting a deductive method of approach and an indirect documentation technique research. About the results of the tests and simulations, we concluded that the implementation of this system will have the same success in any other type of dispenser machine

Evolução morfotectônica do maciço estrutural pereiro, província Borborema

The Northeast relief was described by the Pediplanation Model. This action discards the theoretical basis of post-Cretaceous tectonic evolution of the landscape. Through this model the Massif Pereiro - MP, Borborema Province, was established as part of the Tablelands Area Residual Sertanejos. The present work aims to establish the post- Cretaceous morphotectonic evolution of the MP by geomorphological and geological mapping using Geographic Information System, Remote Sensing and dating of sediments by Single Aliquot Regenerative-dose (SAR). The MP is contained in the core semi-arid, annual precipitation of 600-800 mm / year. The MP is NE-SW, is limited by Shear Zone Jaguaribe (ZCJ) and Portalegre Shear Zone (ZCPa), the same attitude, and crossed by several other shear zones. These shear zones show evidence of brittle Cenozoic reactivation, mostly as normal faults and shallow crustal level. The Quaternary sedimentation around the MP focuses on fault escarpments in a general pattern cascade, where ages decrease from the summits of the steep foothills. The ages of 51 sediment samples indicate a correlation with global climate following pulses: Last Interestadial-UI, the Last Glacial Maximum - LGM and the transition Pleistocene / Holocene, while the latter focus on 18 of 51 samples dated. This study also finds evidence of a new quaternary basin, here called Merejo Basin. Through these results it is concluded that no evidence of post-Cretaceous tectonic evolution of morphological MP, as their retreat along the fault scarps, invariably following the trend of the shear zones. The erosion of cliffs in large time scale is controlled by weakness zones generated by faults on the other hand the erosion of cliffs in short time, with the formation of deposits and colluvial horizons pedogenizados, has climate control. It was also found that in the study area there is a preponderance of past and current tectonic erosion processes on the morphological evolution