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Paraquat (PQ) is an agrochemical agent commonly used worldwide, which is allied to potential risks of intoxication. This herbicide induces the formation of reactive oxygen species (ROS) that ends up compromising various organs, particularly the lungs (by the polyamine uptake system), and the brain (by dopaminergic neuronal cell loss). This study evaluated the deleterious effects of paraquat on the central nervous system (CNS) (changes in physiologic parameters, nociceptive responses, locomotor activity and motor coordination, and expression profile of some inflammatory markers), or peripherally (inflammatory cells in the blood and lungs), with special attempts to assess the putative protective effects of the selective CXCR2 receptor antagonist SB225002 on these parameters. PQ-toxicity was induced in male Wistar rats, in a total dose of 50 mg/kg, given by the intraperitoneal (i.p.) route (10 mg/kg each three days). Control animals received saline solution (10 ml/kg) at the same schedule of administration. Separate groups of animals were treated with the selective CXCR2 antagonist SB225002 (1 or 3 mg/kg, i.p.), administered 30 min before each paraquat injection. The major changes found in paraquat-treated animals were: decreased body weight and hypothermia, nociception behavior, impairment of locomotor and gait capabilities, enhanced TNF-α and IL-1β expression in the striatum, and cell migration to the lungs and blood. Some of these parameters were reversed when the antagonist SB225002 was administered, including recovery of physiological parameters, decreased nociception, improvement of gait abnormalities, modulation of striatal TNF-α and IL-1β expression, and decrease of neutrophil migration to the lungs and blood. Taken together, our results demonstrate that damage to the central and peripheral systems elicited by paraquat can be prevented by the pharmacological inhibition of CXCR2 chemokine receptors. The experimental evidence presented herein extends the comprehension on the toxicodynamic aspects of paraquat, and opens new avenues to treat intoxication induced by this herbicide.

O paraquat (PQ) ? um composto qu?mico bastante utilizado no mundo, o qual ? aliado a potenciais riscos de intoxica??o. Este herbicida induz a forma??o de esp?cies reativas de oxig?nio (ROS) que podem comprometer v?rios ?rg?os, especialmente os pulm?es (atrav?s da recapta??o de poliaminas), e o c?rebro (pela perda de neur?nios dopamin?rgicos). Este trabalho avaliou os efeitos delet?rios do paraquat frente ao Sistema Nervoso Central (SNC) (como mudan?as nos par?metros fisiol?gicos, respostas nociceptivas, atividade locomotora e coordena??o motora, e o perfil de express?o de alguns marcadores moleculares de inflama??o), e perif?rico (como c?lulas inflamat?rias no sangue e pulm?es), com o objetivo de avaliar o poss?vel papel protetor…

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Spinal voltage-gated calcium channels (VGCC) are pivotal regulators of painful and inflammatory alterations, representing attractive therapeutic targets. We examined the effects of epidural administration of the selective P/Q- and N-type VGCC blockers Tx3-3 and Phα1β, respectively, isolated from the spider P. nigriventer, on symptomatic, inflammatory and functional changes allied to cyclophosphamide (CPA)-induced hemorrhagic cystitis (HC) in mice. The effects of P. nigriventer-derived toxins were compared to those displayed by MVIIC and MVIIA, extracted from the cone snail C. magus. HC was induced by a single intraperitoneal injection of CPA (300 mg/kg). The spinal blockage of P/Q-type VGCC by Tx3-3 and MVIIC, or N-type VGCC by Phα1β attenuated nociceptive and inflammatory events associated with HC, including bladder oxidative stress and cytokine production. Moreover, CPA produced an evident increase of bladder TRPV1 and TRPA1 mRNA expression, which was virtually reversed by all the tested toxins. Noteworthy, Phα1β strongly prevented bladder neutrophil migration, besides HC-related functional alterations. Finally, the spinal co-administration of the selective NK1 receptor antagonist CP-96345 heightened Phα1β antinociceptive effects. Our results shed new lights on the role of spinal P/Q and N-type VGCC in bladder dysfunctions, pointing out Phα1β as a promising alternative for treating complications associated to CPA-induced HC.

Os canais de c?lcio voltagem-dependentes (CCVDs), ao n?vel medular, s?o um dos principais reguladores das altera??es inflamat?rias e dolorosas, representando um interessante alvo terap?utico. Com isso, avaliamos os efeitos da administra??o intratecal dos bloqueadores seletivos dos CCVD do subtipo P/Q e N, Tx3-3 e Phα1β, respectivamente, isolados do veneno da aranha P. nigriventer, nas mudan?as sintom?ticas, inflamat?rias e funcionais, relacionadas com a cistite hemorr?gica (CH), induzido pelo quimioter?pico ciclofosfamida (CPA) em camundongos. Os efeitos dos pept?deos provenientes da aranha P. nigriventer foram comparados com os exibidos pelas toxinas MVIIC e MVIIA, obtidas do caramujo C. magus. A CH foi induzida por uma ?nica administra??o intraperitoneal de CPA (300 mg/kg). O bloqueio medular dos CCVD do subtipo P/Q atrav?s da Tx3-3 e MVIIC ou, o bloqueio dos CCVD do subtipo N pela toxina Phα1β atenuou as respostas nociceptivas e inflamat?rias associadas ? CH, incluindo estresse oxidativo e produ??o de citocinas na bexiga. Al?m disso, a CPA produziu um aumento evidente na express?o do RNAm de TRPV1 e TRPA1 na bexiga, o qual foi virtualmente revertido por todas as toxinas. Notavelmente, a isoforma Phα1β reduziu a migra??o de neutr?filos para a bexiga, al?m de reverter as disfun??es da bexiga relacionadas ? CH. Finalmente, a…

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Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES

First identified in Saccharomyces ceresvisie, the sirtuins (SIRTs) are a diverse family of histones deacilases that act as deacetilases, ADP-ribosil transferases, desuccinilases and demalonilases; using nicotinamide adenine dinucleotide (NAD+) as co-substrate. Their regulatory involvement targeting histones, structural proteins and transcription factors implicate them in a broad range of biological processes and raised promising roles as therapeutic targets in apoptosis, oxidative stress and inflammation, among many others. These processes in turn, can be easily modeled in zebrafish (Danio rerio), a model organism with great developmental, genetic and economical advantages. Despite growing interest in this fresh water teleost as model organism and the regulatory and therapeutical potential of sirtuins in inflammation and associated processes, next to nothing is known about sirtuins in zebrafish. In order to contribute to this scenario and accelerate zebrafish potential as screening platform for sirtuins modulators, this work aimed to characterize sirtuins roles in a copper-induced inflammation model in zebrafish larvae. Alterations in locomotor behavior, sirtuin-related genes expression pattern and gene expression of inflammation, oxidative stress and apoptosis markers were observed after copper exposure. In order to further evaluate SIRT1 contribution to this scenario, a SIRT1 knockout line was developed using CRISPR-Cas9 technology, which showed an exarcebated inflammatory response after copper exposures. Additional studies will help to elucidate sirtuin roles in inflammation and associated processes, taking advantage of zebrafish?s translational potential.

Inicialmente identificadas em Saccharomyces cerevisie como reguladores de silenciamento de informa??o, as sirtu?nas (SIRTs) s?o uma diversa fam?lia de histonas desacilases da classe III (HDACs) que atuam como desacetilases, mono-ADP-ribosil transferases, desuccinilases e demalonilases; todas dependentes de nicotinamida adenina dinucleot?deo (NAD+). Presentes em todos os dom?nios de vida e tamb?m em v?rus, as sirtu?nas se tornaram promissores alvos terap?uticos devido seu envolvimento em diversos processos biol?gicos, incluindo apoptose, estresse oxidativo e inflama??o. Estes por sua vez s?o considerados denominadores comuns de diversas patologias e podem ser facilmente estudados utilizando os transl?cidos embri?es e larvas do zebrafish (Danio rerio) como organismo modelo. Apesar do crescente uso deste pequeno tele?steo de ?gua…

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Studies on dental caries demonstrate inflammation on dental pulp tissues following infection. Cytokines are able to activate those cells linked to inflammatory and immune response thus neutralizing potentially aggressive agents and allowing tissue repair. Some of those cytokines, denominated chemokines, could contribute to the establishment of an immunotherapy able to control those cytokines involved with the triggering of dental pulp inflammation. Research on chronic inflammation has provided some relevant insights. However, the role of certain chemokines on acute inflammation is yet not conclusive. This study attempts to unveil the role of the chemokines CCL5/RANTES, CCR5 and RANKL on initial and acute pulpal inflammation. Methods: 18 Wistar rats were subjected to anesthesia. Access was performed on their first lower molars until pulp exposure. They were divided into three experimental groups considering the solution administered: Saline, lipopolysaccharide (LPS) and lipoteichoic acid (LTA) (n=6 each group). Higid second lower molars were used as controls. The cavities were sealed with amalgam and euthanasia occurred after 48 h and the jaws were dissected for histologic evaluation. CCL5/RANTES is expressed in all groups, unlike CCR5, that was not expressed. RANKL appears only in inflammatory cells, including control group. Only RANKL could be expressed during initial pulpal inflammation, being able to detect inflammatory cell activity.

Estudos de c?rie demonstraram aspectos inflamat?rios nos tecidos pulpares decorrentes de infec??o estabelecida. Citocinas seriam capazes de ativar c?lulas ligadas ? resposta inflamat?ria e imune no sentido de neutralizar potenciais agentes invasores e permitir o reparo dos tecidos pulpares. Algumas destas, denominadas quimiocinas, poderiam contribuir no estabelecimento de uma imunoterapia capaz de bloquear aquelas citocinas respons?veis pelo processo inflamat?rio. Na inflama??o cr?nica estas pesquisas j? possuem resultados satisfat?rios. Na inflama??o aguda, os estudos ainda est?o inconclusivos. Este estudo teve como objetivo testar as quimiocinas CCL5/RANTES, CCR5 e RANKL na inflama??o pulpar aguda. M?todos: 18 Ratos Wistar foram anestesiados. Foram feitas cavidades at? a exposi??o pulpar nos primeiros molares inferiores. Eles foram divididos em tr?s grupos onde se administrou solu??o salina est?ril, lipopolissacar?deo (LPS) e ?cido lipoteic?ico (LTA) (n= 6 por grupo). Os segundos molares inferiores h?gidos foram utilizados como controle. As cavidades foram seladas com am?lgama e a eutan?sia foi realizada ap?s 48h. As mand?bulas foram dissecadas para exame histol?gico e da imunoexpress?o das quimiocinas em estudo. Obteve-se como resultados: CCL5/RANTES ? expressa em todos os grupos, ao contr?rio do CCR5, que n?o foi expressa. RANKL aparece apenas em c?lulas inflamat?rias. Somente a express?o…

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Depression is a serious and recurrent disease characterized by anhedonia, loss of interest in daily activities, appetite, and sleep disturbances, reduced concentration and psychomotor agitation. Antidepressant drugs currently used have a very slow onset of action, with that comes the need for fast-acting treatments. Therefore, there is a growing interest in NMDA antagonists as a target for the development of new antidepressant drugs. Considering that the purinergic and dopaminergic systems are involved in anxiety, depression, and sleep, we characterize the role of these signaling pathways on antidepressant effects induced by MK-801 in zebrafish. The animals treated with MK-801 at 5, 10, 15, and 20 ?M during 15, 30, and 60 minutes showed higher permanence in the top area of the tank, in comparison with the control group, indicating an antidepressant effect induced by this drug. The animals treated with MK-801 remained within 2 hours in the top of the tank when treated with 5 ?M MK-801 and 4 hours when treated with 20 ?M MK-801, returning to basal levels 24 hours after exposure.The repeated treatment did not induce cumulative effects, since animals treated daily for seven days showed the same pattern of behavioral response observed from the first day until the 7th day. In order to investigate the action of agonists and antagonists of A1 and A2A receptors and the influence of modulation on adenosine levels in antidepressant effects induced by MK-801, animals were pretreated with Caffeine, DPCPX, CPA, ZM 241385, CGS 21680, AMPCP, EHNA, dipyridamole, and NBTI before the exposure to MK-801 for 30 minutes. The nonselective adenosine receptor antagonist Caffeine (50 mg/kg) and the selective A1 adenosine receptor antagonist DPCPX (15 mg/kg) blocked the behavioral changes induced by MK-801. Dipyridamole (10 mg/kg), a selective inhibitor of nucleoside transport (NT), exacerbates the behavioral changes induced by MK-801. Dopamine receptor antagonists (sulpiride and SCH23390) did not induce changes on the behavioral alterations induced by MK-801. Our results have shown that the antidepressant effects induced by MK-801 in zebrafish are mediated by the activation by A1 adenosine receptor.

A depress?o ? uma doen?a grave, recorrente, caracterizada por anedonia, perda de interesse em atividades di?rias, dist?rbios do apetite e do sono, concentra??o reduzida e agita??o psicomotora. Os f?rmacos antidepressivos utilizados atualmente t?m um in?cio de a??o muito lento, com isso, surge a necessidade de tratamentos de a??o r?pida. Portanto, h? um interesse crescente em antagonistas de receptores NMDA como um alvo para o…

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Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES

Conselho Nacional de Pesquisa e Desenvolvimento Cient?fico e Tecnol?gico - CNPq

Funda??o de Amparo ? Pesquisa do Estado do Rio Grande do Sul - FAPERGS

Neonatal exposure to lipopolysaccharides (LPS) generates a stressful stimulus capable of affecting the development of important systems, which causes lasting behavioral and neuroendocrine alterations. The aim of this study is to evaluate the response to an inflammatory stimulus in Balb/c mice exposed to LPS-induced neonatal stress at different ages and genders. Mice underwent intraperitonial injections on postnatal days 3 and 10 with either LPS (100ug/Kg) or saline solution. After 21 or 60 days of age, either saline solution was injected or an inflammatory stimulus was induced by the injection of 1% carrageenan. Inflammatory cytokines, reactive oxygen species and NETs production were measured in the peritoneal lavage. Our findings indicate that LPS-induced neonatal stress can reduce inflammatory cytokines in young animals, males and females. In adults, however, only females showed the same response pattern. In nLPS group, an increase in NETs production was observed in animals that were 60-days-old when compared to 21-days-old in both genders, which indicates an effect of neonatal stress on the ontogeny of NETs formation. The production of ROS was not affected by neonatal stress, even though an increased production was found among adults regardless of neonatal intervention. The results shown here indicate that LPS-induced neonatal stress can alter cytokine production in response to inflammatory stimuli at different ages, in a gender dependent way. Moreover, it seems like the formation of NETs throughout life is also influenced by alterations undergone during the neonatal period.

A exposi??o neonatal ao lipopolissacar?deo (LPS) gera um estimulo estressor capaz de afetar o desenvolvimento de importantes sistemas, dando origem a altera??es comportamentais e neuroend?crinas duradoras. O objetivo desta disserta??o ? avaliar a resposta a um est?mulo inflamat?rio em camundongos Balb/c submetidos ? estresse neonatal por LPS em diferentes idades e sexos. Os camundongos receberam, no 3? e 10? dias de vida, inje??o i.p. de LPS (100?g /Kg) ou solu??o salina. Ap?s 21 ou 60 dias de vida, os mesmos foram submetidos ? inje??o de solu??o salina ou a um est?mulo inflamat?rio atrav?s da inje??o de carragenina 1%. Foram mensurados no lavado peritoneal citocinas inflamat?rias, esp?cies reativas de oxig?nio e produ??o de Redes Extracelulares de Neutr?filos (NETs). Os resultados encontrados…

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Endodontic aims to prevent and treat diseases of the pulp and periapical tissues. Although the maintenance of pulp vitality is of paramount importance, conservative treatments are not commonly recommended for teeth with pulp exposure by caries. In these situations, conservative treatment is usually indicated for young teeth with open apex. For all the other cases a radical treatment is indicated, the root canal treatment. The reluctance in performing a conservative treatment in a permanent tooth with exposed pulp by caries is due to the difficulty of an accurate diagnosis, as to the condition of pulp inflammation (reversible or irreversible) and in the absence of a compound that promote this tissue to return to homeostasis . Thus, the present study evaluated histologically the effects of Emdogain ? (EMD) and its vehicle, propylene glycol alginate (PGA), in rat infected dental pulp.For this, the pulp chambers of the right lower molars of 24 male Wistar rats were perforated and the cavities were left open to the oral environment for 24 h. Then, the exposed pulp surfaces were direct capped with either EMD or its carrier PGA (n=6), and the cavities were restored with glass-ionomer cement. After the experimental period of 48 hours and 30 days, the animals were euthanized and the dissected mandibles were histologically evaluated. The results showed that a hard tissue barrier was absent in the EMD and PGA groups in the two evaluation periods. At 48 h the groups exhibited similar pulp behavior. At 30 days, the group capped with EMD showed a reduced inflammatory process limited to the exposed area, and degenerative changes on the pulp tissue throughout the length of the root canals. Thus, our results suggest that EMD was not effective on the providing proper wound healing of infected rat molar pulp

A Endodontia tem como objetivo a preven??o e o tratamento das doen?as da polpa e dos tecidos periapicais. Embora a manuten??o da vitalidade pulpar seja de fundamental import?ncia, tratamentos conservadores n?o s?o comumente indicados para dentes com polpa exposta por c?rie. Nestas situa??es, o tratamento conservador costuma ser indicado somente para dentes jovens com ?pice aberto. Para os demais casos indica-se o tratamento radical, a endodontia. A relut?ncia em se realizar um tratamento conservador em um dente permanente com polpa exposta por cavidade profunda de c?rie est? na dificuldade de um diagn?stico preciso quanto ? condi??o pulpar de inflama??o revers?vel e irrevers?vel e na falta de uma subst?ncia que possa fazer esse tecido retornar a homeostase.Neste sentido, o presente estudo avaliou histologicamente os efeitos do Emdogain? (EMD) e o seu ve?culo, propileno glicol alginato (PGA) em polpas dent?rias infectadas de ratos. Para isto foram utilizados 24 molares inferiores de ratos Wistar machos com 8 semanas de idade. A c?mara pulpar…

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Temperament can be regarded as the basis of mood, behavior and personality. It has a strong biological basis, manifested early in the development of the individual, guiding the formation of habits and is relatively stable over time. Although it is known that there are environmental influences, the relationship of temperament with biological markers and social environment is not well defined. Evidence suggests that the temperament and personality traits predict psychiatric disorders and that most of them are recurrent and chronic. Thus, this study aims to investigate the biological and social basis of behavior and in animal models of traits to assess the relationship of temperament with hyperucemia and with self-report of having been bullied in humans. To study the neurobiological basis of this trait, we selected mice with high and low exploration of a central object in an open field. Out of one hundred mice tested, the ten mice with higher (HE) and lower exploratory (LE) activity were evaluated with gene expression (Genechip Mouse Gene 1.0 ST Array Affymetrix) in the striatum and frontal cortex. The results showed 118 and 86 differentially expressed genes (DEGs) in the striatum and frontal cortex, respectively. Through analysis of DEGs biological processes were significantly more enriched in nervous system were development and function and cell-to-cell signaling, particularly in the striatum. These results suggest the involvement of translational and post-translational processes as well as striatal synaptic elements in the trait differences of exploratory behavior. Human studies were conducted with the data collected in a large web-survey on psychological and psychiatric measures (BRAINSTEP). In the study of biological basis of behavior we analyzed temperament in 7.155 males (5.1% hyperuricemic) and 25.225 women (1.8% hyperuricemic). Hyperuricemic subjects scored higher in anger and lower in inhibition and control, but hyperuricemic women also showed a higher emotional sensitivity and a lower degree of volition and coping. Subjects with hyperuricemia present more more externalizing and unstable emotional traits and affective temperaments In the study of the social bases of temperament assessed bullying during childhood and adolescence, through a question on time of exposure to bullying (none, <1 year, 1-3 years and> 3 years). Emotional traits and affective temperaments were evaluated with The Affective and Emotional Composite Temperament Scale (AFECTS). About half of the sample reported exposure to bullying and 10% reported being victimized by peers for longer than 3 years. Longer exposure to bullying was associated with lower Volition, Coping and Control. Bullying victimization was also associated with a much lower proportion of euthymic and hyperthymic types in both genders, which was compensated by an increase mainly in the…

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According to data from the World Health Organization (WHO), stress affects more than 90% of the world's population and is considered a global epidemy. Stress has become an integral part of human life and organisms are constantly subjected to stressful stimuli that change various physiological processes, representing a risk factor for many diseases, such as cancer, cardiovascular, metabolic, infectious and gastrointestinal deseases and depression. The zebrafish (Danio rerio) has many similarities with mammalian in terms of overall organization and the functioning of their stress regulatory systems. The zebrafish hypothalamic-pituitary-interrenal (HPI), analogous to the mammalian hypothalamic-pituitary-adrenal (HPA), has been found in zebrafish and the activation of this pathway is essential for the maintenance of vital functions in response to stressful events. Despite extensive knowledge regarding stress responses in mammals, data on the relationship between chronic unpredictable stress and its effects on purinergic signaling is limited. Purinergic signaling is mediated by ATP and adenosine receptor activation through P2 and P1, respectively. The catabolism of extracellular ATP to adenosine is promoted by the ectonucleotidases, such as Ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDases) and ecto-5 '-nucleotidases (E-5?NT). Adenosine is deaminated by adenosine deaminase (ADA) producing inosine. Thus, these enzymes control the levels of extracellular nucleotides and nucleosides, exerting an influence on purinergic signaling. Considering some models of stress can affect the signalling systems, the objective of this study was to verify whether the unpredictable chronic stress changes ectonucleotidases and adenosine deaminase activities in zebrafish brain. In addition, we analyzed the metabolism of ATP as well as the expression of genes related to ADA, ada1, ada2.1, ada2.2, adaL, adaasi and the effects of agonists and antagonists of adenosine receptors in an unpredictable chronic stress model in zebrafish. Our results demonstrated that there are no changes on ATP (P = 0.1499), ADP (P = 0.3615) and AMP (P = 0.8987) hydrolysis in zebrafish brain membranes submitted to unpredictable chronic stress. In contrast, ecto-ADA activity significantly decreased (26.8%; 8,164 ? 0.78 NH3 min − 1 mg− 1 of protein; p 0.05; n = 5 <) in brain membranes of animals exposed to the unpredictable chronic stress when compared to the control group (11.15 ? 2.16 NH3 min − 1 mg − 1 of protein; p 0.05; n = 5). However, the activity of cytosolic ADA was not changed after the unpredictable chronic stress. Quantitative analysis by RT-qPCR did not show significant changes after chronic unpredictable stress exposure on gene expression in the genes ada1, ada2.1, ada2.2, adaL, adaasi. ATP metabolism in brain membrane preparations of…

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This study investigated whether the spinal or systemic treatment with the lipid resolution mediators resolvin D1 (RvD1), aspirin-triggered resolvin D1 (AT-RvD1) and resolvin D2 (RvD2) might interfere with behavioral and neurochemical changes in the mouse fibromyalgia-like model induced by reserpine. Acute administration of AT-RvD1 and RvD2 produced a significant inhibition of mechanical allodynia and thermal sensitization in reserpine-treated mice, whereas RvD1 was devoid of effects. A similar antinociceptive effect was obtained by acutely treating animals with the reference drug pregabalin. Noteworthy, the repeated administration of AT-RvD1 and RvD2 also prevented the depressive-like behavior in reserpine-treated animals, according to assessment of immobility time, although the chronic administration of pregabalin failed to affect this parameter. The induction of fibromyalgia by reserpine triggered a marked decrease of dopamine and serotonin (5-HT) levels, as examined in total brain, spinal cord, cortex and thalamus. Reserpine also elicited a reduction of glutamate levels in total brain, and a significant increase in the spinal cord and thalamus. Chronic treatment with RvD2 prevented 5-HT reduction in total brain, and reversed the glutamate increases in total brain and spinal cord. Otherwise, AT-RvD1 led to a recovery of dopamine levels in cortex, and 5-HT in thalamus, whilst it diminished brain glutamate contents. Concerning pregabalin, this drug prevented dopamine reduction in total brain, and inhibited glutamate increase in brain and spinal cord of reserpine-treated animals. Our data provide novel evidence, showing the ability of D-series resolvins AT-RvD1, and mainly RvD2, in reducing painful and depressive symptoms allied to fibromyalgia in mice.

O presente estudo investigou o poss?vel efeito do tratamento central ou sist?mico com os mediadores lip?dicos de resolu??o da inflama??o, Resolvina D1 (RvD1), RvD1 ativada pela aspirina (AT-RvD1) e Resolvina D2 (RvD2) sobre mudan?as comportamentais e neuroqu?micas em um model de fibromialgia induzido por reserpina em camundongos. A administra??o aguda de AT-RvD1 e RvD2 produziu um efeito inibit?rio significativo sobre a alod?nia mec?nica e a hipersensibiliza??o t?rmica nos animais tratados com reserpina, sendo que nenhum efeito foi observado quando os animais foram tratados com RvD1. A administra??o aguda de pregabalina, f?rmaco de refer?ncia para o tratamento da fibromialgia, apresentou um efeito antinociceptivo similar ?quele observado para AT-RvD1 e RvD2. Interessante, a administra??o repetida e sist?mica de AT-RvD1 e RvD2 tamb?m preveniu o comportamento depressivo nos animais que receberam reserpina, de acordo com a avalia??o do tempo de imobilidade, enquanto que a administra??o cr?nica de pregabalina n?o apresentou efeito sobre esse par?metro. A indu??o de fibromialgia pela…

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Disturbances in glutamatergic signaling have been proposed as the cause of many diseases of the nervous system. The zebrafish has been considered as an efficient model in the investigation of the neurochemical basis of various disorders, such as schizophrenia and epilepsy. Several neurotransmitter systems have been characterized in zebrafish, including the glutamatergic system. Moreover, a vast repertoire of behavioral responses to drugs has been characterized in particular in adults. However, little information is available about the ability to generate response to classic drugs of glutamatergic action in the early stages of development in zebrafish. Throughout development, ionotropic glutamate receptors have an orderly variability between the subunits that compose them, giving them different pharmacokinetic properties and degree of affinity for their ligands. In this way, we analyzed the locomotor/behavioral profile of zebrafish in response to the glutamate receptor antagonist, MK-801, in different doses in 30, 60, 120 days post-fertilization (dpf) and 2 years post-fertilization animals, as well the effect of caffeine pre-exposure on MK-801 action. Additionally, we analyzed the expression profile of subunits that comprise the NMDA receptor in whole brain of zebrafish during development. Locomotor/behavioral response to kainic acid (KA) was evaluated in different doses at ages 7, 15 and 30 dpf. Also, the pre-exposure to kainic acid in 24 hours post-fertilization (hpf) and 7 and 15 dpf animals was challenged by a second exposure to kainic acid at 2 months post-fertilization The results demonstrated that zebrafish has an age-dependent response to MK-801 and kainic acid, at least on the locomotor/behavior aspects. The peak of locomotor response to MK-801 occurred at 60-120 days post-fertilization, which was partially prevented by caffeine and able to alter the time on upper zone of aquarium as a measure of anxiety. Analysis of gene expression of NMDA receptor subunits in zebrafish brain demonstrated that NR2C and NR2D subunits have later expression in comparison to subunits NR1, NR2A and NR2B. The animals that were exposed to KA showed alterations in locomotor activity without displaying classic convulsive characteristics. However, pre- exposure to 7dpf KA was able to partially prevent the seizure events in response to KA injection (6 mg / K) at 2 months post- fertilization.

Dist?rbios na sinaliza??o glutamat?rgica s?o propostos como a causa de in?meras patologias do sistema nervoso. O peixe-zebra tem sido considerado um eficiente modelo na investiga??o das bases neuroqu?micas de diversos transtornos, tais como a esquizofrenia e a epilepsia. Diversos sistemas de neurotransmiss?o j? foram caracterizados em peixe-zebra, incluindo o sistema glutamat?rgico. Al?m disto, um vasto repert?rio de respostas comportamentais a f?rmacos j?…

Submitted by Setor de Tratamento da Informa??o - BC/PUCRS ([email protected]) on 2015-05-20T12:50:04Z No. of bitstreams: 1 469018 - Texto Completo.pdf: 1309740 bytes, checksum: 2aed89fbf06476e1b1522282c9325099 (MD5)

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The ethanol exposure during early embryonic development can cause morphological and behavioral changes even when ingested in low doses. Growth retardation, microcephaly and mental retardation are some of the features observed in children with FAS (fetal alcohol syndrome) whose mothers ingested ethanol during pregnancy. The mechanisms by which ethanol affects embryonic development and cause such changes have not been fully elucidated. The increase in the extracellular adenosine levels after chronic and acute exposure to ethanol indicates that the purinergic system has an important role in this situation. Adenosine is a neuromodulator that acts through the activation of metabotropic receptors type P1 (A1, A2A, A2B and A3) and can act as an endogenous neuroprotector. In the extracellular space, adenosine can be produced by sequential hydrolysis of adenosine triphosphate (ATP) held by ectonucleotidases, a cascade of a family of enzymes located on the cell surface, which the key process to hydrolyze to adenosine is performed by ecto-5'-nucleotidase. The use of zebrafish in toxicology studies and development offers a number of advantages. Its size and breeding allow the maintenance of a large quantity of fish in a relatively small space. The production of a large number of eggs and the development occurs rapidly, and progresses through well-defined steps. Recent studies have employed the zebrafish as a model for fetal alcohol syndrome and demonstrated that embryonic exposure to ethanol results in phenotypes comparable to those observed in other vertebrate models. The objective of this study was to evaluate the role of adenosine metabolism in the morphological and locomotor parameters of zebrafish larvae exposed to ethanol. The results showed that in addition to morphological damage already known, there is a change in the enzymatic activity of ecto-5'-nucleotidase in larvae of seven days, in both treatments, acute and chronic, independent of gene expression form, which in time was not changed. Pre-treatment with AOPCP, an inhibitor of ecto-5'- nucleotidase, was unable to prevent the morphological damage in a relevant way, although statistically there was a slight prevention. Pre-treatment with dipyridamole, an adenosine transport blocker further worsened the effects caused by ethanol. Considering the changes that occur in extracellular levels of adenosine after exposure to ethanol and the involvement of the purinergic system in early stages of development, our results suggest that there is a combined action of the enzyme ecto-5'-nucleotidase and nucleoside transporters in this rising of extracellular…

Submitted by Setor de Tratamento da Informa??o - BC/PUCRS ([email protected]) on 2015-06-19T11:36:44Z No. of bitstreams: 1 470792 - Texto Completo.pdf: 1695613 bytes, checksum: bfea5d57cf26d524d5b14d7d3ac84cdc (MD5)

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Melanoma is one of the most aggressive malignant tumors, and its incidence has been increasing steadily in recent years. Usually in the early stages, treatment for melanoma is local surgery with reasonable efficiency. However, treatments such as chemotherapies for advanced melanoma have limited benefits, prolonging the patient's life in a few months. Thus the search for more effective therapies for melanoma is necessary. More recent studies suggest that tumor immune response conducted by subtypes of CD4+ T helper cells subsets have an important role in cancer control. According to tumor infiltrating Th17 and Treg cellsand the cytokines they secrete the tumor microenvironment profile may be suggested anti or pro-tumor activities or exerted by these cells. In this study, we investigated the transcriptional markers of CD4+Foxp3+ T cells and CD4+ROR?t+ T cells in draining lymph nodes of animals throughout the melanoma tumor growth and evaluate whether the combined action of cisplatin (cis-diamino-dichloro-platin, CDDP) and TLR2 (peptidoglycan) or TLR3 (acid-Polyribosilic Polyribocytidilic) or TLR4 (lipopolysaccharide) agonists, can change these parameters. The animals were injected with melanoma cell line B16F10 and according tumor progression the tumor draining lymph node (TDLN) were excised for analysis of Treg and Th17 cells by flow cytometry. Furthermore, we analyzed the survival of animals treated with combined therapies. We found an increase in the percentage and absolute number of Th17 and Treg cells in TDLN according tumor progression, which was consistent with previous studies. Our results indicate that treatment with cisplatin promotes tumor growth by increasing Treg and Th17 cells. Treatment with CDDP plus TLR2 agonist significantly decreases the percentage of Th17 cells in TDLN. We demonstrated here, that combinated CDDP and TLR3 or TLR4 agonist therapy impairs tumor growth and modulate the frequency of these cells by decreasing the percentage of CD4+Foxp3+ T cells. In addition, this combination also showed a modest increase insurvivalof the melanoma bearing mice. These results showed that TLRs agonists may be used in combination with cisplatin as a potential adjuvant capable impair tumor growth in melanoma bearing mice.

Melanoma ? um dos tumores malignos mais agressivos, e sua incid?ncia vem aumentando continuamente nos ?ltimos anos. Geralmente em est?gios iniciais, o tratamento para melanoma ? local, por cirurgia, com razo?vel efic?cia. Contudo, os tratamentos para melanoma em est?gios avan?ados por quimioterapia t?m benef?cios limitados, prolongando a vida do paciente em poucos meses.…

Submitted by Setor de Tratamento da Informa??o - BC/PUCRS ([email protected]) on 2016-02-12T17:10:17Z No. of bitstreams: 1 TES_JULIANO_BUSETTI_COMPLETO.pdf: 4728791 bytes, checksum: 9cc2c815f6f8eda49ba630d9796f6ea8 (MD5)

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Regeneration of lost tissues can be obtained in a predictable way by using the Guided Bone Regeneration (GBR) concept. The development of such concept is based on the observation that to regenerate a certain type of tissue, specific cells with the ability to reconstruct such kind of tissue must repopulate the wound. GBR was applied to heal different type of bone defects and the isolation of it by using resorbable and nonresorbable membranes resulted in a predictable healing through the formation of new bone. Nowadays the GBR concept is used for the treatment of multiple clinical situations in dentistry, even with dental implants. Osteoporosis is the most common chronic bone disease and may interfere in the healing of regenerative procedures. The increase in life expectancy results in a larger number of elderly patients referred for bone regeneration and dental implants. Osteoporosis is associated with aging, menopause and chronic use of some types of drugs. Regenerative protocols must be postulated taking into account this category of patients. Limited scientific evidence suggests that osteoporosis can negatively influence bone healing as well as the osseointegration of dental implants. In addition to disease, the use of drugs for its prevention and treatment may affect healing of GBR procedures. Bisphosphonates (BP) are the most frequently used drugs for treatment and prevention of osteoporosis. The drug acts mainly in the inhibition of bone resorption by its action on osteoclasts. Among the commercially prescribed BP, zoledronic acid (ZA) is known to be the most potent of all. In the first paper of this thesis osteoporosis was induced in rats and these animals were submitted to regenerative procedures comparing samples with and without osteoporosis as well as with and without the use of ZA. To assess GBR, critical size defects (CSD) were made in the animals? calvarial bone. Microporous non-resorbable PTFE (polytetrafluorethylene) membranes were used to promote GBR in healthy, osteoporotic and osteoporotic animals treated with ZA. Forty-eight Wistar rats with 6 months of age were included in the study. Experimental osteoporosis was induced by ovariectomy (OVX) associated with hipocalcic diet in 32 animals. Sixteen OVX rats received a single dose of ZA (OZ) while the other 16 osteoporotic rats received no treatment (O). The remaining 16 animals were SHAM operated; the ovaries were exposed but not removed, being considered the control group (C). Six weeks after osteoporosis induction, each animal from the OZ group received a single dose of ZA. One week latter (7…

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Lateral amyotrophic sclerosis (ALS) is a neurodegenerative disease characterized by the selective loss of both lower and upper motoneurons in the spinal cord, brain stem and motor cortex. Loss of motoneurons leads to progressive paralysis, and death in 2 to 5 years. Treatment is based on symptomatic measures and pharmacological therapy available is not curative. Thus, it is of great importance to develop new therapeutic strategies to manage this disease. Alternatively, stem cells to replace could be used to replace degenerating neurons or to stop/delay neuronal death. The aim of this study was to verify if bone marrow mononuclear cells (BMMC) have therapeutic potential in transgenic mice superexpressing SOD1G93A. These animals phenotypic and physiopathological characteristics mimic those of ALS. Seventy-day-old or 110-day-old mice were administered with 107 BMMC in the tail vein. BMMC were obtained from C57BL/6-EGFP or SOD1G93A donors. Control animals received saline. In order to determine disease onset and progression, animals were evaluated in the Rotarod test, by electromyography and had their body weight measured. Survival was also evaluated. Tissue samples were collected for PCR analysis of cell migration. Additional groups of animals were euthanized at 120-days-old for histological analysis and the alkaline comet assay. Our results indicate that EGFPBMMC transplantation in 70-day-old mice (pre-symptomatic) mice prolong survival, preserve motor function and preserve motoneurons in the ventral horn of the spinal cord. However, for mSOD1BMMC the observed effect is intermediary. Furthermore, in 110-day-old (symptomatic) mice, only EGFPBMMC prolonged survival. This effect was more discrete than the one observed for pre-symptomatic-treated animals. Finally, systemically administered BMMC migrate into the spinal cord where fragments of their DNA were identified by PCR. There were no differences between the experimental groups in the electromyographical evaluation or DNA integrity measured by the alkaline comet assay. Our results suggest that BMMC have therapeutic potential in ALS since we observed improved motor performance and prolonged survival in animals that received the transplant. Nonetheless, outcomes were better when intervention was early and the transplanted cells did not express the mutated SOD1. Thus, our data represent a step forward in making cell-based therapy available for ALS patients. However, questions associated to the time of intervention and the source of the cells should be carefully addressed.

A esclerose lateral amiotr?fica (ELA) ? uma doen?a neurodegenerativa caracterizada por uma perda seletiva de neur?nios motores na medula espinhal, tronco encef?lico e c?rtex motor. A perda de motoneur?nios d? in?cio a uma paralisia progressiva, levando o paciente a ?bito em 2 a 5 anos. O tratamento se baseia…

Submitted by Setor de Tratamento da Informa??o - BC/PUCRS ([email protected]) on 2016-08-22T16:27:06Z No. of bitstreams: 1 TES_FERNANDA_FRANCINE_ZIMMERMANN_COMPLETO.pdf: 4145272 bytes, checksum: e7185015e9927f4db21344a6bf065ef8 (MD5)

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Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES

Several psychiatric and neurological diseases are characterized by impairments in social function, such as autism spectrum disorders (ASD) and schizophrenia (SCZ). In this study, we conducted a behavioral screening at different times of zebrafish development at 6, 30, 70 and 120 dpf (postfertilization days) to establish a social interaction deficit model induced by valproic acid (VPA) at 48 ?M concentration to investigate social behavior, locomotion, aggression and anxiety. To analyze the social behavior of each fish was placed in an experimental tank. On one side of the experimental tank, an empty fish tank was placed; on the other side, a tank of identical size held 15 zebrafish, which were designed the ?stimulus fish?. We quantify the time of the experimental fish from the side of the tank "fish stimulus" in relation to empty tank. The locomotion of the animals was assessed by evaluating the following parameters: distance traveled, average speed, number of crossings and the time spent in each tank position (bottom vs. upper levels) was considered an index of anxiety. To analyze the aggression the animals were individually placed in an experimental tank. A mirror was placed at the side of the tank at an angle of 22.5? to the backwall of the tank so that the left vertical edge of the mirror touched the side of the tank and the right edge was further away.Thus, when the experimental fish swam to the left side of the tank, their mirror image appeared closer to them. indicating preference for the opponent.Our results showed that exposure to VPA induced changes on locomotor activity and anxiety in different periods of development in zebrafish. In addition, VPA-treated animals presented a deficit in social interaction to 70 dpf and 120 dpf. Exposure to VPA did not affect aggression in the adult stage after 70 dpf and 120 dpf. This study also investigated the purinergic signaling in a model of embryonic exposure to VPA, which induced deficit in social interaction in adult zebrafish. This study demonstrates the first evidence that exposure to VPA in embryonic zebrafish in 120 dpf can modulate the hydrolysis of nucleotide and nucleoside and adenosine deamination in zebrafish brain membranes. In addition, we analyzed the effects of oxytocin, the oxytocin receptor agonist (carbetocin) and oxytocin receptor antagonist (L-368,899) on the reversal of behavioral effects induced by MK-801 in zebrafish regarding behavior social, such as, changes in social interaction and aggression. These results support the…

Submitted by Setor de Tratamento da Informa??o - BC/PUCRS ([email protected]) on 2016-11-10T16:14:13Z No. of bitstreams: 1 TES_MARIA_DAS_GRACAS_VILLELA_RODRIGUES_COMPLETO.pdf: 3711034 bytes, checksum: 8599c9dfdb61b14f16b029441393ea84 (MD5)

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The investigation stems from the realization of the importance that the computer science area exerts a process of integration with the Health Sciences in that it offers mimicry possibilities station bodily functions which provides technology to support scientific research. As these research in the areas of Health Sciences can not always be carried out with humans for ethical reasons and even the use of animals has been restricted, technological innovations make it ever more necessary to advance such research. Thus, this thesis aims to determine whether the image display as vector digital methodology results in more efficiency and wider use compared to the analog image. The methodology used, with the participation of 210 travel volunteer medical students of PUCRS three class members. In each class, students were randomized into two groups of 35 students, the control group was exposed to an analog image sciatic nerve in the rat division, while the test group was exposed to the same nerve imaging, but vectored in Inkscape program, compared to a division of the sciatic nerve photograph captured by a scanning electron microscope. Each group viewed the received image, comparing it with the electron microscope image, identifying this picture the names of the nerves that are part of the division of the sciatic nerve. Later the control group viewed digital images to a post-test and with the test group answered a questionnaire of receptivity of the methodology. We used the comparison and statistical method to perform the analyzes which confirmed the greater efficiency of digital images with respect to the analog images, validating the use of digital images and digital methods.

A investiga??o surge da constata??o da import?ncia que a ?rea de Ci?ncias da Computa??o exerce num processo de integra??o com as Ci?ncias da Sa?de na medida em que oferece possibilidades de mimetiza??o de fun??es org?nicas posto que propicia recursos tecnol?gicos para o apoio das pesquisas cient?ficas. Como estas pesquisas nas ?reas das Ci?ncias da Sa?de nem sempre podem ser realizadas com seres humanos por raz?es ?ticas e mesmo a utiliza??o de animais tem sido restringida, as inova??es tecnol?gicas fazem-se sempre mais necess?rias para o avan?o de tais pesquisas. Assim, esta tese tem por objetivo determinar se a visualiza??o de imagem vetorizada como metodologia digital resulta em mais efici?ncia e mais ampla utiliza??o em compara??o com a imagem anal?gica. A metodologia utilizada, contou com a participa??o de 210 alunos volunt?rios do curso de medicina da PUCRS, integrantes de tr?s…

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The effects on kinin B1 receptor (B1R) deletion were examined on bone regeneration in streptozotocin (STZ)-type-1 diabetic mice, subjected to a model of femoral critical-size defect. Diabetes induction in wild-type C57/BL6 (WT C57/BL6) mice was allied to decrease of body weight and hyperglycemia, in relation to the non-diabetic group of the same strain. The lack of B1R did not affect STZ-elicited body weight loss, although it partially prevented hyperglycemia. Type-1 diabetic mice presented a clear delay in bone regeneration, with large areas of loose connective tissue within the region corresponding to the defects, when compared to wide areas of newly-formed woven bone in non-diabetic WT C57/BL6 mice. Notably, either non-diabetic or diabetic B1R knockout (B1RKO) mice displayed bone regeneration levels comparable to that seen in control WT C57/BL6 mice. The improved bone regeneration in animals lacking B1R was further confirmed by analysis of collagen contents. WT C57/BL6 STZ-diabetic mice presented a marked reduction of collagen contents within the bone defect gap, whereas diabetic B1RKO displayed collagen levels comparable to those observed in non-diabetic WT C57/BL6 or B1RKO mice. The enhanced bone regeneration in diabetic mice lacking B1R does not seem to be associated to lessened osteoclast activity, as no prominent difference was detected in the levels of tartrate-resistant acid phosphatase (TRAP) positivity, or even in the immunolabeling for the proteins of the RANK/RANKL/OPG system thoughout all the experimental groups. Data brings novel evidence on the relevance of B1R under type-1 diabetes, especially concerning its role in bone regeneration after surgical procedures

Os efeitos da dele??o g?nica do receptor B1 das cininas na regenera??o ?ssea foram avaliados em camundongos com diabetes tipo 1 induzida por estreptozotocina, submetidos a um modelo de defeito cr?tico no f?mur. Como resultado da indu??o de diabetes nos camundongos wild-type C57/BL6, houve um decr?scimo do peso corporal e hiperglicemia em rela??o ao grupo n?o-diab?tico da mesma cepa. Os animais diab?ticos, com aus?ncia do receptor B1 apresentaram perda do peso corporal e, uma preven??o parcial da hiperglicemia. Camundongos diab?ticos do tipo 1 tiveram um atraso na regenera??o ?ssea, apresentando um tecido conectivo desorganizado na regi?o correspondente ao defeito cr?tico, quando comparados a extensas ?reas de tecido ?sseo rec?m-formado em camundongos WT C57/BL6 n?o diab?ticos. Camundongos B1R nocaute, diab?ticos ou n?o diab?ticos, exibiram n?veis de regenera??o ?ssea semelhantes aos observados no grupo controle WT C57/BL6. A melhora na regenera??o ?ssea nos animais sem o receptor B1 foi confirmada pela an?lise da quantidade de col?geno. Camundongos WT C57/BL6 diab?ticos apresentaram uma redu??o acentuada da distribui??o de col?geno na regi?o do defeito…

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Introduction : The prenatal period is critical for the development and maturation of several organ systems essential. Objective : To evaluate the effects of prenatal stress on behavioral responses, as well as possible structural changes and standard cell lung in an experimental model with Balb/c. Materials and Methods : We used female Balb/c primiparous. After identification of pregnancy, the animals were divided into 3 groups: CTLE (control), PNS 1 (stress every other day from the 8th day of pregnancy) and PNS 2 (stress from day 15 of pregnancy until birth). The prenatal stress was accomplished through containment. The animals were weighed at birth, weaning and day 10 (day 21). As adults, we analyzed the behavior of fear/anxiety through field tests (AC) and elevated plus maze (EPM) was performed and bronchoalveolar lavage (BAL) and lung histopathology. Results : No differences were found in relation to animal weight among the three groups. Behavioral analysis of the males in the test AC and EPM, showed no significant difference between groups PNS 1 and PNS 2 relative to CTLE. In the analysis of the test AC, females PNS 1 group showed a decrease in the total distance covered (P <0.001) increased time on the periphery (p <0.001) and decreased time the center (p <0.001) compared to the group CTLE. The test EPM in females was not significantly different among the three groups. The analysis of the cellular profile in BAL and lung histology, there were no differences between groups. Conclusion : The prenatal stress induces changes in the behavior of fear/anxiety only in Balb/c mice and the stress model from the eighth day of pregnancy, suggesting that the effects of the programming are possible in this model. On the other hand, prenatal stress caused no alterations in basal lung.

Introdu??o : O per?odo pr?-natal ? de suma import?ncia para o desenvolvimento e a matura??o de diversos sistemas e ?rg?os essenciais. Objetivo : Avaliar os efeitos do estresse pr?-natal sobre as respostas comportamentais, assim como poss?veis altera??es estruturais e do padr?o celular no pulm?o em um modelo experimental com camundongos Balb/c. Materiais e M?todos: Foram utilizadas f?meas Balb/c prim?paras. Ap?s a identifica??o da prenhez, os animais foram divididos em 3 grupos: CTLE (controle), PNS 1 (estresse em dias intercalados a partir do 8? dia da prenhez) e PNS 2 (estresse a partir do 15? dia da prenhez at? o nascimento). O estresse pr?-natal foi realizado atrav?s de conten??o. Os animais foram pesados ao nascimento, dia 10 e no desmame (dia 21). Quando adultos, foram analisados o comportamento de medo/ansiedade por meio dos testes de campo aberto (CA) e labirinto em cruz elevada (LCE) e foi realizado lavado broncoalveolar (LBA) e an?lise histopatol?gica do pulm?o. Resultados : N?o foram encontradas diferen?as em rela??o ao peso dos animais entre os…

Submitted by Setor de Tratamento da Informa??o - BC/PUCRS ([email protected]) on 2015-07-16T11:47:41Z No. of bitstreams: 1 472323 - Texto Parcial.pdf: 121966 bytes, checksum: 2381428855b2dc0b8ef271a500527bef (MD5)

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Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES

Introduction: The exposure to early life stress (ELS) has been associated with different psychopathologies in adulthood such as mood- and anxiety-related behaviors. In animal research, the maternal separation paradigm has been widely used to investigate the longterm effects of ELS. Considering the negative effects of ELS on development, evidences suggesting that exercise could attenuate or even reverse such effects are beginning to emerge. This article aimed to investigate the impact of physical exercise on anxiety-like behavior and spatial memory in mice exposed to maternal separation. Method: Litters were assigned to one of 4 groups: The MS animals were subjected to a procedure where pups were separated from their dams daily for 180 minutes, from postnatal days (P) 2 to 15. The exercise protocol was performed at P24 and consisted of one week of habituation to treadmill and 3 weeks of exercise, with 60 min of duration at 10 m/min for 5 days a week. The performance in an open field test was evaluated to assess locomotor activity and anxiety-like behavior. Object recognition was also performed to investigate the effects of MS and exercise on spatial memory. Results: Both maternal separation and exercise increased locomotor activity in the open field. However, anxiety-like behavior was not affected by MS or exercise. In object recognition, all groups presented the same exploratory behavior. However, MS impaired the capability to recognize the new object, suggesting impairment in spatial memory. In time, MS mice that exercised were able to reverse the negative effects of MS, showing a performance similar to the control group (AFR). Taken together, our results suggest that the disruption of the normal development course?here via maternal separation paradigms?is harmful to a good development and may result in cognitive and behavioral difficulties in adulthood. Furthermore, the early engagement in a program of exercise can be effective in reversing the impairments of ELS.

Introdu??o: A exposi??o ao estresse no in?cio da vida est? associada com diferentes psicopatologias na fase adulta como transtornos de humor e ansiedade. Em pesquisas com modelos animais, o paradigma de separa??o materna ? amplamente utilizado para investigar os efeitos de longo prazo do estresse no in?cio da vida. Considerando os efeitos negativos do estresse no desenvolvimento, come?am a surgir evid?ncias que o exerc?cio poderia atenuar ou at? mesmo reverter os efeitos delet?rios do estresse. Este trabalho se prop?s a investigar o impacto do…

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Coordena????o de Aperfei??oamento de Pessoal de N??vel Superior (CAPES)

Conflitos entre ativistas e pesquisadores da comunidade biom??dica, como o incidente envolvendo o resgate dos beagles do Instituto Royal, em 2013, envolvem quest??es ??ticas e cient??ficas significativas. O estudante e o profissional de Ci??ncias Biol??gicas e da Sa??de (Bioci??ncias), ao exercer atividades docentes, t??cnicas ou de pesquisa, deve ser capaz de posicionar-se criticamente e tomar decis??es socialmente respons??veis frente a essas quest??es que est??o intimamente ligadas as suas pr??ticas profissionais e pessoais. A presente disserta????o tem como objetivo investigar as dimens??es axiol??gicas e cient??ficas na forma????o de profissionais das Bioci??ncias com ??nfase na prepara????o para tomada de decis??es socialmente respons??veis em rela????o ao modelo animal ainda bastante utilizado em atividades cient??ficas, bem como propor alguns princ??pios de design que podem ser assumidos como bases para a constru????o inicial de interven????es educacionais com esse foco. Nesse sentido, caracterizamos a problem??tica do uso de animais em atividades cient??ficas como uma quest??o sociocient??fica que requer uma aten????o especial. Abordamos a perspectiva curricular Ci??ncia, Tecnologia e Sociedade (CTS) como modo de contextualizar o ensino das Bioci??ncias e contribuir para o desenvolvimento da capacidade de tomar decis??es socialmente respons??veis dos estudantes. Al??m disso, realizamos uma an??lise das potencialidades da ??tica animal consequencialista como conte??do axiol??gico desses processos formativos, a partir da sua caracteriza????o e das cr??ticas oriundas de perspectivas ??ticas ???concorrentes???. No que tange a dimens??o cient??fica, tratamos das quest??es relacionadas ??s contribui????es da teoria evolutiva darwinista, em especial a de descend??ncia comum, na forma????o para tomada de decis??o em rela????o ao uso do modelo animal no fazer e ensinar ci??ncias.

Clashes between activists and researchers in the biomedical community as the incident involving the rescue of the beagles from the Royal Institute, in 2013, involving ethical and scientific issues significant. The student and the professional of Biological Sciences and Health Issues (Bioscience), to undertake teaching activities, technical or research, should be able to position themselves critically and make socially…

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This research was conducted at the Federal Institute of Education, Science and Technology of Amap? (IFAP / Macapa Campus) in 2013 with eighteen students from the Food Technology Course, in high school level, in the modality of Education Program for Young People and Adults/ PROEJA, which were attending the third module. The teacher-researcher was part of the group studied and aimed to investigate how experimentation fosters student learning of vocational education in the form of Education for Young People and Adults, using as theme the concept of chemical kinetics. The framework of this research was based on Ausubel's meaningful learning. To check whether there was success in learning not only due to the generating theme in question using experimentation, but also by the ability to articulate the (re)constructed knowledge in contextualization. The research was characterized as an ethnographic case study as it was based on both of qualitative and quantitative methodology, questionnaires, registration and description of dialogues. After analysis and discussion of the results, we found that learning occurred significantly and allowed students to correlate Chemistry not only to their academic trainings, but also to their citizenship practices, serving as a basis for later knowledge acquisition.

Esta pesquisa foi realizada no Instituto Federal de Educa??o, Ci?ncia e Tecnologia do Amap? (IFAP/Campus Macap?) em 2013 com dezoito alunos do Curso T?cnico em Alimentos, de n?vel m?dio, na modalidade da Educa??o Jovens e Adultos/PROEJA que cursavam o terceiro m?dulo do curso. A professora-pesquisadora fez parte do universo pesquisado e tinha como objetivo pesquisar como a experimenta??o favorece a aprendizagem dos estudantes da educa??o profissionalizante na modalidade da Educa??o Jovens e Adultos, usando como tema gerador o conceito de cin?tica qu?mica. A base referencial desta pesquisa foi a aprendizagem significativa de Ausubel. Para verificar se houve ?xito na aprendizagem dos alunos n?o apenas pelo tema gerador em quest?o utilizando a experimenta??o, mas tamb?m pela capacidade de articular os saberes (re) constru?dos utilizando-se da contextualiza??o. A pesquisa caracterizou-se como um estudo de caso etnogr?fico tendo como natureza a utiliza??o da metodologia quali-quantitativa, com aplica??o de question?rio, registro e descri??o dos di?logos ocorridos. Ap?s a an?lise e discuss?o dos resultados obtidos verificamos que a aprendizagem ocorreu de forma significativa e permitiu aos alunos correlacionassem a qu?mica n?o apenas a sua forma??o acad?mica, mas a sua forma??o como cidad?o servindo como base para…

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Different approaches have been advocated for implementation of conservative treatment of the pulp tissue, usually employing inflammation control and the application of compounds with therapeutic potential on the pulp. The Resolvin E1 (RvE1) is a lipid mediator capable of regulating inflammatory routes that do not involve the blockage of enzymatic intermediates. The aim of this study was to evaluate the effect of the topical application of RvE1 on dental pulps exposed to the oral environment. To this end, 42 male Wistar rats (n=6 per group/period) had the pulps of the right mandibular first molars assessed and then left exposed to the oral environment for 24 hours. After this period, topical medication either with 0.1% ethanol (vehicle of RvE1), RvE1 or a corticosteroid was applied onto the pulp tissue, and the teeth were then sealed with silver amalgam. The effects of the tested protocols were assessed by histology after 24 and 72 hours. Untouched teeth were used as reference for relative analysis and grading of the alterations observed in test groups. RvE1 induced significant reduction and containment of pulp inflammation with less extensive damage compared to either 0.1% ethanol or corticosteroid (P<0.05). Within the conditions tested none of the tested drugs promoted identical pulp tissue features compared to the observed in untouched teeth (P<0.01). The results presented herein have uncovered protective roles for RvE1 in pulp inflammation, suggesting that it may be a candidate for a novel therapeutic strategy for preservation of its vitality.

Diferentes abordagens t?m sido advogadas para implementa??o do tratamento conservador do tecido pulpar, usualmente empregando o controle da inflama??o e a aplica??o de compostos com potencial terap?utico sobre a polpa. A Resolvina E1 (RvE1) ? um mediador lip?dico capaz de regular rotas inflamat?rias que n?o envolvem o bloqueio de intermedi?rios enzim?ticos. O objetivo deste estudo foi avaliar o efeito t?pico da RvE1 sobre polpas dentais expostas ao meio oral. Para esta finalidade, 42 ratos machos Wistar (n = 6 por grupo/per?odo), tiveram as polpas dos primeiros molares inferiores direitos acessadas e deixadas expostas ao meio oral por 24 horas. Ap?s este per?odo, medica??o t?pica com etanol 0.1% (ve?culo da RvE1), RvE1 ou corticoster?ide foi aplicada sobre o tecido pulpar e os dentes foram selados com am?lgama de prata. Os efeitos dos protocolos testados foram avaliados histologicamente ap?s 24 e 72 horas. Dentes intactos foram utilizados como refer?ncia para an?lise das altera??es verificadas nos grupos experimentais. RvE1 induziu significativa redu??o e conten??o da inflama??o com danos pulpares menos extensos em compara??o ao etanol 0.1% ou corticoster?ide (P<0.05). Nenhum dos f?rmacos testados promoveu caracter?sticas pulpares id?nticas ?s observadas nos dentes intactos (P<0.01).…

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This study deals with the category of Experience (Erfahrung) in the writings of Walter Benjamin. To this end, it initially investigates the context lived by the author in the modern period with its technological and scientific changes and the influences that he received from the philosopher Franz Rosenzweig, aspects that decisively will mark his own understanding about that category. Secondly, it searches out to highlight the understanding of Benjamin on the subject and the constellation of elements that are related to it, among which we can point the question of time, narrative, tradition, memory and thresholds situations. Still showing the impoverishment of the very notion of Experience against the advent of modernity and the impacts of World War I, as well as its consequent reduction of the scope of experiment occurred in that period. Also adding to this, an instrumental conception of language and philosophy which is now used only as a guide to scientific knowledge. Such point also involves a criticism of the theory of knowledge of Immanuel Kant and the interpretations of it carried out by the school of Marburg. That?s the reason why it discusses, finally, the urgent need to recognize the poverty of Experiences in which we live and the requirement to recover the Experience to its fullest to the speech, especially the philosophical, in order to resume the expressive character of philosophy itself, once consigned to oblivion, as well as its ability to think in temporality.

O presente estudo versa sobre a categoria de Experi?ncia (Erfahrung) no pensamento de Walter Benjamin. Para tanto, investiga inicialmente o contexto vivido pelo autor no per?odo moderno com suas transforma??es tecnol?gicas e cient?ficas e as influ?ncias por ele recebidas do fil?sofo Franz Rosenzweig, aspectos que de forma determinante ir?o marcar a sua pr?pria compreens?o a respeito de tal categoria. Num segundo momento, busca destacar, ent?o, a compreens?o de Benjamin sobre o tema, bem como a constela??o de elementos que a este est?o relacionados, dentre os quais se podem apontar a quest?o do tempo, da narrativa, da tradi??o, da mem?ria e das situa??es limiares. Evidenciando ainda o empobrecimento da pr?pria no??o de Experi?ncia frente ao advento da modernidade e aos impactos da Primeira Guerra Mundial, assim como sua consequente redu??o ao ?mbito do experimento ocorrida nesse per?odo. Agregando a isso tamb?m uma concep??o instrumental da linguagem e da filosofia que passa a ser utilizada exclusivamente como guia para o conhecimento cient?fico. Ponto que envolve ainda uma cr?tica ? teoria do…

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CAPES

Este memorial, intitulado Eu, o outro e tantos n??s: experimenta????es liter??rias no Ensino Fundamental, apresenta os resultados do projeto de interven????o aplicado na Escola S??nia Regina de Souza, situada no munic??pio de Cama??ari, cujo objetivo foi discutir as diversidades e as quest??es identit??rias, a fim de promover a toler??ncia e o respeito dentro e fora do contexto escolar, al??m de fomentar a autonomia e a autoria dos sujeitos envolvidos. Em aten????o ao problema que se apresentou ?? pesquisa - a saber: mutila????o dos sujeitos sociais, que resistiam ??s pr??ticas de produ????o escrita em sala, mas escreviam com desenvoltura em di??rios, grafites, desenhos espalhados pelos cadernos e carteiras - foram elaboradas duas oficinas de cria????o, intituladas, respectivamente, 1- Eu e o outro e 2- Tantos n??s, atrav??s das quais os estudantes se expressaram por meio de linguagens diversas. A Literatura no campo expandido, a escrita de si e a autoria foram pilares para a pesquisa, ancorada nos estudos de Andruetto (2012), Aguilar e C??mara (2017), Salles (2006), Pato (2012), Quilici (2014), Rosa (2013), Josso (2012) e (2007), Machado (2009) e (1998), Krauss (1984) e Cesar (2002). Os dados desta pesquisa autoetnogr??fica foram apresentados a partir de rodas de conversa, produtos das oficinas de cria????o e dos di??rios escritos pelos alunos. Os resultados alcan??ados demonstram que os sujeitos da pesquisa d??o sentido ?? produ????o escrita em linguagens diversas quando s??o oportunizados momentos de cria????o e cuidado, despertando mem??rias e afec????es de corpos falantes, escreventes e criativos, que t??m aprendido a se enxergar no outro e a dizer muito sobre si.

This memorial, titled ???Me, the Other one and so many of Us: literary experiments in Elementary school???, presents the results of the intervention project applied at school S??nia Regina de Souza, situated in Cama??ari, whose objective was to discuss the diversity and identity issues, in order to promote tolerance and respect inside and outside the school context, and promote the autonomy and authorship of the subjects involved. In response to the problem presented to the research: mutilation of social subjects, who resisted to the practices of writing in classroom, but have been writing with ease in diaries, graffiti,…

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This dissertation presents the development and evaluation of a prototype for the stimulus of the olfactory system, which will be employed in the study of neuroimages gathered by functional magnetic resonance image (fRMI). Basic requirements for the prototype include: safety, human physiology and environmental compatibility, homogeneous release of aerosolized stimuli, accurate control of pressure and flow conditions, support for up to three distinct substances, and substance mixing capability. Digital image processing techniques were used in evaluation process through the usage of Matlab in order to better assess the reliability and reproducibility in the evaluation of the of the samples released under controlled constant pressure of 3.5+/- 0.3 kgf/cm?, different flows (4 l/min, 6 l/min, 8 l/min and 10 l/min), and different duration periods (10s, 15s, 20s, 30s, 60s and 90s). Charts with the image profiles, histograms and statistical data were generated and analyzed. The delay in the system, important information for any study in fRMI, was measured using an oxygen sensor and custom software solution. Experiments for the determination of the amount of substance required and the real capability of mixing substances were performed with parameters based on the results from the digital image processing analysis.

Esta disserta??o de mestrado apresenta o desenvolvimento e a avalia??o de um prot?tipo para estimular o sistema olfativo, o qual ser? empregado em estudos de neuroimagens obtidas pela modalidade de resson?ncia magn?tica funcional. Para o desenvolvimento do prot?tipo foram definidos requisitos b?sicos que o sistema deveria possuir: seguran?a, compatibilidade com o ambiente e com as caracter?sticas fisiol?gicas humanas, dispensar amostra aerossolizada, precis?o para controlar e regular vaz?o e press?o, capacidade para tr?s subst?ncias distintas e possibilidade de mistur?-las. A avalia??o utilizou t?cnicas de processamento de imagens digitais com a utiliza??o do software Matlab com a finalidade de estudar a confiabilidade e reprodutibilidade na quantifica??o da amostra dispensada utilizando press?o fixa de 3,5 +/- 0,3 kgf/cm? e as vari?veis fluxo (4 l/min, 6 l/min, 8 l/min e 10 l/min) e tempo (10s, 15s, 20s, 30s, 60s e 90s). Os resultados foram analisados atrav?s de gr?ficos de perfil dos pixels, histogramas e dados estat?sticos das imagens. O atraso do sistema, dado fundamental para pesquisas em resson?ncia magn?tica funcional, foi medido com a utiliza??o de um sensor de oxig?nio e um software desenvolvido em LabVIEW. Experimentos para medir o consumo e a possibilidade de misturar as amostras foram realizados utilizando os resultados obtidos com a valida??o por processamento de imagens digitais.

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The research work was carried out at the State Integrated Center of Rural Education, located in the Northwest of the state of Esp?rito Santo. CEIER is a full-time school that has as its pedagogy the education of the field. The school has the secondary education, being this integrated to the technical course in farming. The research had as a procedure bibliographical survey, documentary analysis and field research. The research was qualitative in nature, with semi-structured questionnaires being applied to the students (questionnaire applied on-line) and to the 24 final students of the year 2016. The results of the questionnaires were analyzed using the reference framework of Franco (2008). It was also carried out a survey of the work of conclusion of internship defended in the year 2010 to 2015 with the objective of verifying in which area of agriculture the majority of the works take place. The main objective of this research was to investigate and evaluate how the activities carried out in the internship and the practical activities of experimentation developed in the Work of Completion Internship contributed to a greater learning of the students and if there was also a contribution in the professional qualification of the students graduating and of the technical course in agriculture. The results indicate that the students, both the graduates and the graduates consider it important to carry out the internship for a better training in the vocational course, and that the accomplishment of the internship work contributes significantly to the understanding of the theoretical contents learned during the course, an experience with scientific work, to solve problems, contributing not only to the learning teaching process but also guaranteeing a greater self-confidence for the future agricultural technician and student of higher education

O trabalho de pesquisa foi realizado no Centro Estadual Integrado de Educa??o Rural, localizado no Noroeste do estado do Esp?rito Santo. O CEIER ? uma escola de tempo integral que tem como proposta pedagogia a educa??o do campo. A escola possui o ensino m?dio, sendo este integrado ao curso t?cnico em agropecu?ria. A pesquisa teve como procedimento levantamento bibliogr?fico, an?lise documental e pesquisa de campo. A pesquisa foi de natureza qualitativa, tendo a coleta de dados realizada atrav?s de question?rios semi estruturados aplicado aos estudantes egressos (question?rio aplicado de forma on line) e aos 24 estudantes concluintes do ano de 2016. Os resultados dos question?rios foram analisados utilizando o referencial de Franco (2008). Tamb?m foi…

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A tese aborda a quest??o da auto-educa????o a partir da perspectiva de Friedrich Nietzsche e outros pensadores, que o tomaram como refer??ncia para pensar filosoficamente possibilidades de uma aprendizagem voltada para fazer da vida uma obra de arte. A quest??o problematizada ?? como esta aprendizagem pode ocorrer de modo cada vez mais aut??nomo configurando uma arte de viver direcionada para a poetiza????o da exist??ncia. A auto-educa????o ?? pensada como parte de uma autopoiesis, um processo de subjetiva????o mais abrangente quanto aos aspectos da exist??ncia em que a aprendizagem ?? experimentada no sentido proposto por Nietzsche para fazer da vida uma obra de arte, tornando-se poeta da pr??pria exist??ncia e tomando o corpo como fio condutor desse processo. A perspectiva de Nietzsche ?? considerada juntamente com algumas outras que se apropriaram dela para formularem suas pr??prias concep????es, tais como, principalmente: Oswald de Andrade, pela Antropofagia como vis??o de mundo voltada para a apropria????o seletiva da alteridade subjetiva; Martin Heidegger, pela hermen??utica do acontecimento apropriativo na cria????o po??tica; Michel Foucault, pela genealogia dos processos de subjetiva????o, abrangendo desde a antiguidade greco-romana at?? a contemporaneidade, que o permitiu formular a quest??o da est??tica da exist??ncia; Gilles Deleuze e Felix Guattari, pela cartografia da autopoiesis como processo de subjetiva????o singularizante, modulado por paradigmas est??ticos apropriados; e Dante Galeffi, pela proposta poem??tico-pedag??gica de uma educa????o transdisciplinar para o fazer inventivo do ser-sendo, que configura a vita poem??tica. Essas e outras perspectivas foram usadas para elaborar a proposta de uma educa????o autopoi??tica do corpo criador que Nietzsche indicou como o ser pr??prio, e foi denominado nesta tese de corpoema. A educa????o autopoi??tica do corpoema ?? pensada ao longo da experimenta????o da autopoiesis em alguns campos da exist??ncia, nos quais se constitui a est??tica da exist??ncia corpo??tica: os campos de experimenta????o da habita????o do espa??o de vida, da din??mica corporal dos impulsos, das rela????es de poder, das valora????es afetivas, das linguagens de express??o e da compreens??o dos…

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Funda????o de Amparo ?? Pesquisa do Estado da Bahia (FAPESB)

O trabalho a seguir busca trazer enunciados gerais para o trabalho experimental sob a ??tica da pedagogia hist??rico-cr??tica. Entendemos que, para a utiliza????o da pedagogia hist??rico-cr??tica como referencial, o trabalho precisa ser estruturado de modo a contemplar a tr??ade forma-conte??do-destinat??rio, de maneira que nenhum desses elementos deva ser pensado separadamente. Essa tr??ade foi a base para elabora????o dos enunciados. De modo geral, esses enunciados servem como auxiliares de professores e???ou pesquisadores que trabalham com a pedagogia hist??rico-cr??tica e buscam articular a experimenta????o em sua pr??tica escolar. A experimenta????o pode ser pensada, na dimens??o da forma, como um recurso did??tico que auxilia os professores de ci??ncias. Na dimens??o do conte??do, ?? visto como um aparato que se fez presente no pr??prio processo de constru????o dos conhecimentos cient??ficos. Desse modo, podemos anunciar que um trabalho experimental, baseado na perspectiva cr??tica e nas dimens??es de forma, deve ser planejado de modo a vir a contribuir para o desenvolvimento omnilateral dos indiv??duos. Entendemos que em uma sociedade t??o esvaziada de conceitos e t??o focada na unilateralidade (como esta vem se apresentando), faz-se necess??ria uma forma????o que seja pautada nas m??ltiplas determina????es e nas m??ximas possibilidades. Na dimens??o do conte??do, ressaltamos a import??ncia do entendimento acerca dos conte??dos cl??ssicos, e at?? mesmo o pr??prio conceito de cl??ssico, de modo que anunciamos que o trabalho experimental nessa dimens??o deve ser planejado de modo que contribua para o entendimento de cl??ssico. Na dimens??o do destinat??rio, pensamos em cada n??vel do ensino b??sico, buscando aliar as especificidades de cada um deles para que a experimenta????o possa vir a caminhar junto com a educa????o escolar. Para esse fim, anunciamos que a experimenta????o deve ser planejada de maneira que contribua diretamente para o desenvolvimento da atividade principal, tanto na educa????o infantil como no ensino fundamental e m??dio. Isto, uma vez que a atividade principal ?? a atividade que mais contribui para o desenvolvimento das crian??as, afinal, cada fase apresentar?? uma atividade diferente. Entendemos que esse trabalho ?? uma primeira aproxima????o, podendo assim ser a porta de entrada para outras pesquisas nessa ??rea.

The following work seeks to bring general…

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This paper discusses the approaches and departures on the concepts of authors, professors of chemistry and middle school students about the use of inquiry in the classroom. Thus, the central problem of the following research question: What aspects approach and depart aspects in relation to the theoretical insights of Education and Science Education, Chemistry teachers and high school students on the use of inquiry in the classroom? The investigation was conducted with 38 students and 20 teachers from public and private network of Porto Alegre and Porto Alegre metropolitan area. For data collection, questionnaires were applied with research subjects and subsequently analyzed using Textual Discourse Analysis. The analysis allows us to understand how the question is present in the classroom and what the comparative between theorists, teachers and students. It was possible to identify that inquiry based teaching does not occur that investigated schools and reconstructive question was not identified in the responses to questionnaires. In conclusion, it points to the need for teacher training for this research, both theoretical and practical, work under the assumptions of Demo (2007) and consequently makes the student an active researcher, moreover, the use of reconstructive questioning.

O presente trabalho aborda os afastamentos e as aproxima??es em rela??o ?s concep??es de te?ricos, professores de Qu?mica e estudantes do Ensino M?dio a respeito do uso da pergunta em sala de aula. Assim, o problema central da investiga??o ? a seguinte pergunta: Que aspectos se aproximam e que aspectos se afastam em rela??o ?s percep??es de te?ricos da Educa??o e Educa??o em Ci?ncias, professores de Qu?mica e estudantes do ensino M?dio sobre o uso da pergunta na sala de aula? A investiga??o foi realizada com 38 estudantes e 20 professores de escolas das redes p?blica e privada de Porto Alegre e da Grande Porto Alegre. Para a coleta de dados, foram aplicados question?rios com os sujeitos de pesquisa, os quais, posteriormente, foram analisados por meio de An?lise Textual Discursiva. A an?lise permitiu compreender como a pergunta est? presente na sala de aula e comparar as percep??es de te?ricos, professores e estudantes. Foi poss?vel identificar que a educa??o pela pesquisa pouco ocorre nas escolas investigadas e que o questionamento reconstrutivo n?o foi identificado nas respostas aos question?rios respondidos. Dentre as conclus?es, aponta-se a necessidade da qualifica??o da forma??o do professor, tanto te?rica quanto pr?tica, para que tenham condi??es de trabalhar a pesquisa de acordo com os pressupostos de Demo (2007),…