Efeito de ligantes do receptor NOP no modelo animal de mania induzido por metilfenidato

Bipolar disorder is a chronic psychopathology that reaches from 1 to 4% of the world population. This mood disorder is characterized by cyclical mood changes, in which an individual alternates between states of depression and mania. Mania is described in the literature as an abnormal state of exacerbation of humor, in which the subject presents an expansive, euphoric behavior, but with increased irritability, psychomotor agitation and a feeling of invincibility, which will contribute to risks exposure. The treatment of this psychopathology is complex and it is not effective in all cases, and it evokes many side effects. In this respect, the system of Nociceptin/Orphanin FQ (N/OFQ) can be studied as a possible therapeutic target for the treatment of bipolar disorder, due to its modulatory role on monoaminergic systems and on mood. This study aims to investigate the effect of NOP receptor ligands in an animal model of mania induced by methylphenidate. To this aim, locomotor activity was assessed in an open field, in mice treated with methylphenidate (10 mg/kg, sc, 15 min). Valproate (300 mg / kg, ip, 30 min), standard treatment of mania, prevented methylphenidate-induced hyperlocomotion. The acute treatment with the antagonist of NOP receptor UFP-101 (1-10 nmol, icv, 5 min) per se did not affect the spontaneous locomotion of mice, but it was able of attenuating hyperlocomotion induced by methylphenidate. The acute treatment with N/OFQ (1 and 0.1 nmol, icv, 5 min) did not alter the distance moved, but when tested at a dose of 1 ηmol, N/OFQ slightly reduced methylphenidate-induced hiperlocomotion. In conclusion, the administration of UFP-101 and N/OFQ produced antimanic-like actions. Furthermore, these data suggest that the system of N/OFQ performs a complex modulation of voluntary movement, and consequently on dopaminergic neurotransmission.

O teatro do oprimido e sua contribuição na formação da criança com transtorno do déficit de atenção com hiperatividade

This research investigates and reports the contributions of the Theatre of the Oppressed and its techniques as a therapeutic resource in the education of children with Attention Deficit Disorder with Hyperactivity. In the first chapter organize one studying theoretical seeking to conceptualize and understand the Learning, Attention Deficit Hyperactivity Disorder, seeking to better understand the behavior and the behavior of children with ADHD. Researching on the symptoms, causes and effects of this syndrome. Trace a relationship between familyschool- specialists in an attempt to prove the importance of family support in the teachinglearning process and treatment of these children. In the second chapter start conceptualizing theater, the relationship between work-Theatre-Education Therapy, explain the difference between the theatrical stage and the therapeutic stage. Account the importance of theater games in the classroom and its contribution to social and educational training of the child. Justify the choice of the Theatre of the Oppressed recognizing him as the primary method for this research, because it is a set of exercises, games and techniques that help the child regain equilibrium relations, developing autonomy, encourages creativity and spontaneity, freeing them from their oppression. Besides being an efficient transformation behavior, improving behavior, allowing the inclusion of children in society. It is verified the effectiveness of the method and techniques in their work with children Municipal School Professor. Antonio Severiano in Natal / RN, allowing these children develop body awareness, working senses, thought, memory, inhibition, teaching to expose your point of view, understand and deal with their emotions, respecting its limits and develop their motor and cognitive skills

Avaliação do estresse oxidativo induzido por superfícies de titânio

Commercially pure Titanium (cp Ti) is a material largely used in orthopedic and dental implants due to its biocompatibility properties. Changes in the surface of cp Ti can determine the functional response of the cells such as facilitating implant fixation and stabilization, and increased roughness of the surface has been shown to improve adhesion and cellular proliferation. Various surface modification methods have been developed to increase roughness, such as mechanical, chemical, electrochemical and plasma treatment. An argon plasma treatment generates a surface that has good mechanical proprieties without chemical composition modification. Besides the topography, biological responses to the implant contribute significantly to its success. Oxidative stress induced by the biomaterials is considered one of the major causes of implant failure. For this reason the oxidative potential of titanium surfaces subjected to plasma treatment was evaluated on this work. CHO-k1 cells were cultivated on smooth or roughed Ti disks, and after three days, the redox balance was investigated measuring reactive oxygen species (ROS) generation, total antioxidant capacity and biomarkers of ROS attack. The results showed cells grown on titanium surfaces are subjected to intracellular oxidative stress due to hydrogen peroxide generation. Titanium discs subjected to the plasma treatment induced less oxidative stress than the untreated ones, which resulted in improved cellular ability. Our data suggest that plasma treated titanium may be a more biocompatible biomaterial.

Proteômica diferencial da Chromobacterium violaceum em resposta ao estresse oxidativo induzido por peróxido de hidrogênio

The β-proteobacterium Chromobacterium violaceum is a Gram-negative, free-living, saprophytic and opportunistic pathogen that inhabits tropical and subtropical ecosystems among them, in soil and water of the Amazon. It has great biotechnological potential, and because of this potential, its genome was completely sequenced in 2003. Genome analysis showed that this bacterium has several genes with functions related to the ability to survive under different kinds of environmental stresses. In order to understand the physiological response of C. violaceum under oxidative stress, we applied the tool of shotgun proteomics. Thus, colonies of C. violaceum ATCC 12472 were grown in the presence and absence of 8 mM H2O2 for two hours, total proteins were extracted from bacteria, subjected to SDS-PAGE, stained and hydrolysed. The tryptic peptides generated were subjected to a linear-liquid chromatography (LC) followed by mass spectrometer (LTQ-XL-Orbitrap) to obtain quantitative and qualitative data. A shotgun proteomics allows to compare directly in complex samples, differential expression of proteins and found that in C. Violaceum, 131 proteins are expressed exclusively in the control condition, 177 proteins began to be expressed under oxidative stress and 1175 proteins have expression in both conditions. The results showed that, under the condition of oxidative stress, this bacterium changes its metabolism by increasing the expression of proteins capable of combating oxidative stress and decreasing the expression of proteins related processes bacterial growth and catabolism (transcription, translation, carbon metabolism and fatty acids). A tool with of proteomics as an approach of integrative biology provided an overview of the metabolic pathways involved in the response of C. violaceum to oxidative stress, as well as significantly amplified understanding physiological response to environmental stress. Biochemical and "in silico" assays with the hypothetical ORF CV_0868 found that this is part of an operon. Phylogenetic analysis of superoxide dismutase, protein belonging to the operon also showed that the gene is duplicated in genome of C. violaceum and the second copy was acquired through a horizontal transfer event. Possibly, not only the SOD gene but also all genes comprising this operon were obtained in the same manner. It was concluded that C. violaceum has complex, efficient and versatile mechanisms in oxidative stress response

Análise da Expressão de APE1 após Estresse Oxidativo Induzido em Células Proficientes e Deficientes na Via de Reparo por Excisão de Nucleotídeos

Riboflavin is a vitamin very important in aerobic organisms, as a precursor of many coenzymes involved in the electron transporter chain. However, after photosensitization of riboflavin with UV or visible light, it generates reactive oxygen species (ROS), which can oxidize the DNA. The repair of oxidative lesions on DNA occurs through the base excision repair pathway (BER), where APE1 endonuclease plays a central role. On the other hand, the nucleotide excision repair pathway (NER) repairs helix-distorting lesions. Recently, it was described the participation of NERproteins in the repair of oxidative damage and in stimulation of repair function fromAPE1. The aim of this research was to evaluate the cytotoxic effects of photosensitized riboflavin (RF*) in cells proficient and deficient in NER, correlating with APE1 expression. For this propose, the cells were treated with RF* and it was performed the cell viability assay, extraction of whole proteins, cells fractionation, immunoblotting, indirect immunofluorescence and analysis of polymorphisms of BER gens. The results evidenced that cells deficient in XPA and CSB proteins were more sensitive to RF*. However, XPC-deficient cells presented similar resistance to MRC5- SV cells, which is proficient in NER. These results indicate that XPA and CSB proteins have an important role on repair of oxidative lesions induced by RF*. Additionally, it was evidenced that single nucleotide polymorphisms (SNPs) in BER enzymes may influence in sensitivity of NER-deficient cell lines. Concerning the APE1 expression, the results showed that expression of this protein after treatment with RF* only changed in XPC-deficient cells. Though, it was observed that APE1 is recruited and is bound to chromatin in MRC5-SV and XPA cells after treatment with RF*. The results also showed the induction of DNA damage after treatment with RF*, through the analysis of-H2AX, since the treatment promoted an increase of endogenous levels of this phosphorylated protein, which acts signaling double strand-break on DNA. On the other hand, in XPC-deficient cells, regardless of resistance of RF*, the endogenous levels of APE1 are extremely reduced when compared with other cell lines and APE1 is not bound to chromatin after treatment with RF*. These results conclude that RF* was able to induce cell death in NERdeficient cells, where XPA and CSB cells were more sensitive when compared with MRC5-SV and XPC-deficient cells. This last result is potentially very interesting, since XPC-deficient cell line presents low levels of APE1. Additionally, the results evidenced that APE1 protein can be involved in the repair of oxidative damage induced by RF*, because APE1 is recruited and bound strongly to chromatin after treatment.

Proteômica comparativa de linhagens celulares humanas expostas a estresse oxidativo induzido por riboflavina fotossensibilizada

Reactive oxygen species (ROS) are continuously generated and can be derived from cellular metabolism or induced by exogenous factors, in addition, have the capacity to damage molecules like DNA and proteins. BER is considered the main route of DNA damage oxidative repair, however, several studies have demonstrated the importance of the proteins participation of other ways to correct these injuries. NER enzymes deficiency, such as CSB and XPC, acting in the damage recognition step in the two subways this system influences the effectiveness of oxidative damage repair. However, the mechanisms by which cells deficient in these enzymes respond to oxidative stress and its consequences still need to be better understood. Thus, the aim of this study was to perform a proteomic analysis of cell lines proficient and deficient in NER, exposed to oxidative stress, in order to identify proteins involved, directly or not, in response to oxidative stress and DNA repair. For this, three strains of human fibroblasts, MRC5-SV, CS1AN (CSBdeficient) and XP4PA (XPC-deficient) were treated with photosensitized riboflavin and then carried out the differentially expressed proteins identification by mass spectrometry. From the results, it was observed in MRC5-SV increase expression in most of the proteins involved in cellular defense, an expected response to a normal cell line subjected to stress. CS1AN showed a response disjointed, it is not possible to establish many interactions between the proteins identified, may be one explanation for their sensitivity to treatment with riboflavin and other oxidants and increased cell death probably by induction of pro-apoptotic pathways. Already XP4PA showed higher expression of apoptosis-blocking proteins, as there was inhibition or reduced expression of others involved with the activation of this process, suggesting the activation of an anti-apoptotic mechanism in this lineage, which may help explain the high susceptibility to develop cancers in XPC individuals. These results also contribute to elucidate action mechanisms of NER in oxidative damage and the understanding of important routes in the oxidative stress correlation, repair and malignant tumors formation

Distúrbios do sono em pacientes com transtorno depressivo

To evaluate sleep disorder complaints in outpatients with depressive disorder from a general hospital. Methods: An observational, cross-sectional study was carried out with a study sample composed of 70 patients (44 women and 26 men) with diagnosis of depressive disorder, according to the DSM-IV criteria. The patients were interviewed and evaluated by the Identification Questionnaire, the Sleep Habits Questionnaire and the Beck Depression Inventory (BDI). Results: In this study, 50 (71.3%) patients had recurrence of sleep disorder complaints. Mean BDI score was 35.83+8.85, with significant differences between patients with (38.50+8.70) and without (29.60+7.80) recurrence (p<0.05) and among patients with 1, 2, 3 and >3 episodes (p<0.05). In this study, 49 (70%) patients had insomnia and 21 (30%) had subjective excessive sleepiness. Significant differences were observed between the mean duration in months of the sleep disorders (7.16+2.10) and the depressive disorder (6.12+1.90) (p<0.05). Discussion: In the study sample, recurrence of sleep disorder complaints was high and significantly associated with severe depression. Insomnia was prevalent and the mean duration of sleep disorders was higher in relation to depressive disorder

Interações comunicativas entre uma professora e um aluno com transtorno invasivo do desenvolvimento na escola regular

Inclusion of students with autism in regular education settings is a topic that has not been much explored by the national scientific literature. This matter is complex and, due to the extent of various aspects involved, it is essential to delimitate a focus of investigation. The direction taken by this study was to evaluate the effects of an intervention program in the communicative interactions between a student with autism and his teacher in a regular classroom. Data were collected in an elementary private school, located in the city of Natal, Rio Grande do Norte during the 2010 academic school year. The study included a teacher and a non-vocal, 10-year-old student diagnosed with autism. A quasi-experimental A-B research design was employed. During the intervention program the teacher was trained to use Naturalistic Teaching Strategies and Alternative and Augmentative Communication (AAC) resources to increase the frequency of interactions with the student during three classroom routines (entry time, snack and pedagogical activity). The results indicated qualitative and quantitative changes in the interactions of the dyad after the implementation of the intervention program. The student began to use pictograms to communicate with the teacher in two of the three routines investigated. The frequency of AAC use was also observed in the teacher‟s repertoire, especially when the student failed to understand gestures and words. The teacher positively evaluated the intervention program

Análise dos efeitos de um plano educacional individualizado no desenvolvimento acadêmico e funcional de um aluno com transtorno do espectro do autismo

Given the paradigm of inclusive education, the presence of students with autism spectrum disorder in regular schools has become more significant in recent years. Studies have revealed, however, deficits in academic participation of these students in these settings. Among the factors contributing to this phenomenon include poor teacher training and the lack of strategies to promote curriculum access. The aim of this study was to develop an instrument that would promote academic inclusion of a student with autism through procedures that could simultaneously empower the teacher. In this perspective, the study aimed to analyze the effects of an Individualized Educational Plan (IEP), developed collaboratively with teachers, on the academic and functional development of a student with autism in an early childhood education setting. Data were collected in a private school located in the city of Natal in Rio Grande do Norte, in the course of the academic year 2012. In addition to the student with autism, one teacher, a specialized educator, and four teacher aides participated in the study. The research used a single subject quasi-experimental design (AB) as well as qualitative methods of data analysis. The study was conducted in three phases: characterization, baseline and intervention. The first comprised interviews with the child´s parents and teachers, as well as the identification of two routines focus of intervention. In the second phase, the amount of time the student spent engaged in the selected routines during baseline was analyzed. In the third phase, the researcher prepared, collaboratively with the teachers, an individualized educational plan (IEP) for the student. Finally, the IEP was implemented by the teachers. The results indicated qualitative and quantitative changes in student´s participation in academic and functional tasks after the intervention program

A prática pedagógica de professores de alunos com transtorno de déficit de atenção/hiperativadade

This study is inserted at the Line of Strategical Research of Thinking and Knowledge production which scientific projects about the relation of thinking and knowledge production are realized. The accomplishment of this dissertation involved an empiric research at a school of the municipal district of Natal RN. Our purpose was to investigate the practice of the staff working with students who present Disabilities and Attention Deficit Hyperactivity (DADH) at regular classes due to the organization of thinking in pedagogical strategies. The object of this study is presented at the center of the questions which involves the conscious analysis of the problems and needs that emerge at the school. Considering the specialty of the theme, we choose a methodology whose focus is the dialogue and the sharing of meanings with the partners of this research through the observation of the activities developed at class/school and interviews/conversations with six teachers of first and second cycles of primary education. According with the study, some theoretician presumptions of Mr. Freire (2001), Mr. Nóvoa (1995), Mr. Bohm (2005) and son on. The results reveled at the research indicate the fragility of a continuous formation directed to the development of critical-reflexive thinking of the teachers.The teachers revel conceptions due to formation, pedagogical practices and the relation with the parents and coordinators, through their performances and speeches, allowing us to identify some pedagogical strategies used. We identified some negative response about the process of learning-developing of these pedagogical strategies such as the one we call unconcern . The strategy of sitting the student at the front row chairs can have positive and negative responses depending on the way the teacher act and follow the student. Other strategies identified as positive response bringers at the learning-developing process and that should be reinforced by the staff are the playful and the group assignments . At this perspective, the school needs to develop a collective project between the pedagogical team and teachers to overcome the needs of all students, and as a consequence, of the staff and improve the positive strategies, minimizing the negative ones and allowing the organizations of new strategies that promotes the improvement of learning-teaching process of the students with DADH

A influência da estimulação transcrâniana por corrente contínua nos parâmetros de dano muscular induzido pelo exercício

A estimulação transcraniana por corrente contínua (ETCC) é uma técnica não invasiva que apresenta características anti-fadigante e analgésica. Com o objetivo de testar seus efeitos sobre a diminuição da força e do aparecimento da dor muscular de início tardio (DMIT), apresentados após um evento de dano muscular induzido pelo exercício (DMIE), foi utilizado um estudo clínico de caráter experimental, controlado, randomizado e duplo-cego. A amostra foi composta por 24 jovens do sexo masculino, aparentemente saudáveis (19,7±1,8 anos; 23,6±3,65 IMC), os quais foram alocada, de forma aleatória e estratificada, nos seguintes grupos: G1: grupo controle; G2: grupo de estimulação após o dano e G3: grupo com estimulação antes e após o dano muscular. Os dados foram submetidos à estatística descritiva e análise de variância ANOVA, adotando-se um nível de significância de 5%. O aumento nos níveis séricos de CK (56.18%) e LDH (24,15%) comprovou a ocorrência do DMIE. Em contrapartida, após a análise de variância para comparação dos tratamentos aplicados, pode-se observar que não houve diferenças significativas nos níveis de CK (p= 0,3514) e força muscular (p= 0,9702). A DMIT transcorreu como esperado, mas sem diferença significativa entre os grupos (p= 0,4861). Estes dados demonstraram que a ETCC não foi capaz de modular a DMIT e a diminuição da força muscular após o DMIE em jovens aparentemente saudáveis

Efeitos do treinamento aeróbio sobre sinais precoces do remodelamento do ventrículo esquerdo induzido pelo diabetes Mellitus experimental

Our aim was to investigate the effects of an aerobic training program on adverse and early left ventricle (LV) remodeling, using an experimental model of short-term type 1 diabetes (T1D). Wistar rats were divided in 4 groups: sedentary control (SC), trained control (TC), sedentary diabetic (SD) and trained diabetic (TD). T1D was induced by streptozotocin (45 mg/kg). The training program consisted of 4 weeks running on a treadmill (13 m/min, 60 min/day, 5 days/week). At the end of the experiments, hearts were collected for analysis of morphology and transcriptional profile of LV, by focusing on its remodeling. Deaths were recorded during the 4-week period. We verified high mortality among animals of DS group, whereas it was significantly reduced in DT group. DS group also showed an increase in cross-sectional area of cardiomyocytes and fibrosis. TD group exhibited reduction in measures of cardiac trophism, but with respect to collagen content, it was similar to CS group. Analysis of gene expression related to cardiac remodeling revealed decreased expression of collagen I and III, as well as low expression of MMP-2 in DS group. TD group showed decreased levels of mRNA for MMP-9, and unchanged gene expression of MMP-2 when compared with the CS group. The expression of MMP-2 and TGF-1 were increased in CT group. The ratio between gene expression of collagen I and III was increased in the CT group and decreased in diabetic groups. These results establish early changes of the structure and transcriptional profile of LV myocardium. Moreover, they indicate that aerobic exercise training plays specific protection against mechanisms responsible for cardiac damage observed in T1D

Efeito da crioterapia e da laserterapia na resposta ao dano muscular induzido pelo exercício excêntrico: ensaio clínico e randomizado

Exercise-induced muscle damage mainly affects individuals who returned to physical activity after a time without practicing it or had some kind of exhaustive exercise, particularly eccentric exercise. To evaluate the effect of cryotherapy and laser therapy in response to muscle damage induced by eccentric exercise on the biceps muscle. This was a randomized clinical trial consisting of 60 female subjects. All subjects initially underwent an evaluation consisting of perimetry, measurement of pain sensation (via algometry and visual analogue scale), electromyography and dynamometry. Then the subjects performed an exercise protocol on the isokinetic dynamometer consisting of 2 sets of 10 eccentric elbow flexors contraction at 60 °/s. Completed this protocol, an intervention was held according to a previously random group distribution: control group (no intervention), cryotherapy group and laser therapy group. Finally, subjects were re-evaluated immediately and 48 hours after the intervention protocol, except for Visual Analogue Scale (VAS), which was also evaluated 24 hours after exercise. The circumference of the limb, the pain sensation (VAS and algometry), the muscle activation amplitude (via Root Mean Square - RMS), median frequency, peak torque normalized per body weight, average peak torque, power and work were analyzed. The median frequency immediately after the intervention protocol on the cryotherapy group was the only variable that showed inter and intra-group differences; the remaining variables showed only intragroup differences. The perimetry values did not change immediately after the protocol on the groups which underwent cryotherapy and laser therapy, however, there was an increase after 48 hours; algometry values decreased in all groups for 48 hours and the VAS values increased 24 and 48 hours also for all groups. Regarding RMS no significant change was observed. For dynamometry, peak torque normalized per body weight and average peak torque had a similar behavior, with a reduction in the post protocol that has remained after 48 hours. For the power and work, a decrease was observed immediately after the protocol with a further reduction after 48 hours. Cryotherapy and laser therapy does not alter the muscle damage response, except for the perimetry values immediately after exercise.

Caracterização comportamental e distribuição de neurônios inibitórios em um modelo animal de autismo induzido por ácido valpróico

Autism comprises a heterogeneous group of neurodevelopmental disorders that affects the brain maturation and produces sensorial, motor, language and social interaction deficits in early childhood. Several studies have shown a major involvement of genetic factors leading to a predisposition to autism, which are possibly affected by environmental modulators during embryonic and post-natal life. Recent studies in animal models indicate that alterations in epigenetic control during development can generate neuronal maturation disturbances and produce a hyper-excitable circuit, resulting in typical symptoms of autism. In the animal model of autism induced by valproic acid (VPA) during rat pregnancy, behavioral, electrophysiological and cellular alterations have been reported which can also be observed in patients with autism. However, only a few studies have correlated behavioral alterations with the supposed neuronal hyper-excitability in this model. The aim of this project was to generate an animal model of autism by pre-natal exposure to VPA and evaluate the early post-natal development and pre-puberal (PND30) behavior in the offspring. Furthermore, we quantified the parvalbumin-positive neuronal distribution in the medial prefrontal cortex and Purkinje cells in the cerebellum of VPA animals. Our results show that VPA treatment induced developmental alterations, which were observed in behavioral changes as compared to vehicle-treated controls. VPA animals showed clear behavioral abnormalities such as hyperlocomotion, prolonged stereotipies and reduced social interaction with an unfamiliar mate. Cellular quantification revealed a decrease in the number of parvalbumin-positive interneurons in the anterior cingulate cortex and in the prelimbic cortex of the mPFC, suggesting an excitatory/inhibitory unbalance in this animal model of autism. Moreover, we also observed that the neuronal reduction occurred mainly in the cortical layers II/III and V/VI. We did not detect any change in the density of Purkinje neurons in the Crus I region of the cerebellar cortex. Together, our results strengthens the face validity of the VPA model in rats and shed light on specific changes in the inhibitory circuitry of the prefrontal cortex in this autism model. Further studies should address the challenges to clarify particular electrophysiological correlates of the cellular alterations in order to better understand the behavioral dysfunctions

Compreendendo a experiência de pessoas portadoras de transtorno mental: histórias de vidas severinas repletas de possibilidades

This study aims to understand the experience of people suffering from mental disorder. The patients are enrolled in a mental health ambulatory clinic in the city of Natal (RN). Mental disorders are growing rapidly in the contemporary world and are a source of intense mental suffering. Besides patients being strongly marked by a history of isolation and prejudice, they have been the target of real atrocities committed in the name of preservation of a supposed normality. The understanding and treatment of this disorder is influenced by cultural and historical inferences, depending on the period in which it is experienced. Semi-directed Interviews were conducted with a group of users, with the emphasis on giving voice to their uniqueness and individuality, highlighting how each one perceives his or her own experience. These were recorded and later transcribed by identifying the core of meanings. The results were analyzed under the gaze of the Humanist Phenomenology Existential perspective, which aims to unravel the phenomenon, without truths from volatility, highlighting the existence of the mental disorder as a way of living, being permeated by suffering mental and influenced by social problems, assuming contours very particular to each individual. Some progress has been perceived, even by users, with respect to the change of paradigm in the way of care, but still there is a consistent emphasis on medical and drug use. The changes point to the need for offering services to replace the asylum hospital model, and in addition to accept the bearer of mental disorder as a citizen, a bearer of rights who should be accepted and respected by society. Despite the pain expressed and its close liaison with suicide, their reports are full of perspectives and attitudes of confrontation facing life, pointing to new possibilities to be, recreating itself