19 resultados para Polimorfismo de Nucleotídeo Único

em Universidade Federal do Rio Grande do Norte(UFRN)


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A Síndrome de Berardinelli-Seip (SBS) é um distúrbio raro do metabolismo dos lipídios, caracterizada pela ausência quase total de tecido adiposo subcutâneo, hipertrigliceridemia, hipoleptinemia e diabetes insulino resistente ou lipoatrófico. Sua etiologia envolve implicações hipotalâmicas, alterações nos receptores de insulina e mutações nos genes AGPAT2, Gng3lg, CAV1 e PTRF. O tecido adiposo secreta diversas substâncias, tais como: leptina, resistina, adiponectina, esteróides, TNF , IL-6, PAI-1, angiotensinogênio, IGF-1. Muitas delas estão associadas ao diabetes mellitus tipo 2, obesidade e hipertensão. Os PPARs são fatores transcricionais pertencentes à superfamília de receptores nucleares ligantes ativados. Sabe-se que o PPAR , é importante para o metabolismo lipídico e glicídico e que o ligante natural do PPAR é derivado do ácido graxo. Nesse sentido, foram avaliados 24 pacientes portadores da SBS, provenientes do Estado do Rio Grande do Norte, com a mediana das idades de 18,5 anos (0,55 a 47 a), sendo 9 (37,5 %) do gênero masculino e 15 (62,5 %) do gênero feminino. Quanto ao grupo étnico, foram classificados em caucasóides (brancos) 21 (87,5 %) e negróides 3 (12,5 %) pacientes. Foram feitas avaliações clínico-endocrinológica, bioquímica, hormonal, molecular e o estudo dos polimorfismos Adiponectina ADIPOQ, PPARγ2 Pro12Ala, LPL-PvuII, APOC3-SstI e LDLR-AvaII em portadores da SBS. Nesta população nós não encontramos nenhuma associação de parâmetros lipídicos e glicídicos com os polimorfismos LPL-PvuII, APOC3-SstI e LDLR-AvaII. Porém, observamos associação entre Adiponectina ADIPOQ e PPARγ2 Pro12Ala e níveis lipídicos mais elevados, sugerindo um papel biológico para estes fatores, indicando estudos mais aprofundados

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Matrix metalloproteinase-7 (MMP-7) and -9 (MMP-9) modulate important functions strictly related to the development, invasion and metastasis of several human cancers among them the squamous cell carcinoma of the tongue (SCCT). However, individual genetic factors such as the functional single nucleotide polymorphisms (SNPs) influence the pattern of protein expression of these MMPs and thus may be related to the variability observed in the clinical behavior of patients with SCCT. In this context, the present cross-sectional study aimed to evaluate the association between the frequency of the functional SNPs MMP-7 -181 A/G and MMP-9 -1562 C/T and the clinical (age, gender and metastasis) and pathological (malignancy histological grading and immunohistochemistry expression) features of SCCT cases. Genotyping of these SNPs were performed by PCR-RFLP on DNA samples from 71 cases of SCCT and 60 individuals without cancer who constitute the control group. Among the results of this research, it was observed that the frequency of the polymorphic alleles MMP-7 -181 G and MMP-9 -1562 T in SCCT patients was 28% and 12%, respectively, and the frequency of the heterozygotes A/G (PR = 2.00; p < 0.001) and C/T (PR = 1.54; p = 0.014) were significantly higher in the patient group than in the controls. The prevalence of patients carrying the combination of SNPs studied was significantly associated with SCCT cases (PR = 2.00; p = 0.011) and metastasis (PR = 2.00; p < 0.001). Furthermore, with the frequency of SNPs analyzed, the age, gender, histological grading and immunoreactivity of MMP-7 and MMP-9 formed clinical and pathological parameters relevant to the identification of population subgroups more related to the development of SCCT and metastasis. Based on these results, it is suggested that the protein expression levels of MMP-7 and -9 substantially influence the balance between their pro- and anticancer biological functions and hence the clinicopathological profile of the squamous cell carcinoma of the tongue

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Base excision repair (BER) and nucleotide excision repair (NER) pathways play critical role in maintaining genome integrity. Polymorphisms in BER and NER genes which modulate the DNA repair capacity may affect the susceptibility and prognosis of oral cancer. This study was conducted with genomic DNA from 92 patients with oral squamous cell carcinomas (OSCC) and 130 controls. The cases were followed up to explore the associations between BER and NER genes polymorphisms and the risk and prognosis of OSCC. Four single-nucleotide polymorphisms (SNPs) in XRCC1 (rs25487), APEX1 (rs1130409), XPD (rs13181) and XPF (rs1799797) genes were tested by polymerase chain reaction – quantitative real time method. The GraphPad Prism version 6.0.1 statistical software was applied for statistical analysis of association. Odds ratio (OR), hazard ratio (HR), and their 95 % confidence intervals (CIs) were calculated by logistic regression. Kaplan-Meier curve and Cox proportional hazard model were used for prognostic analysis. The presence of polymorphic variants in XRCC1, APEX1, XPD and XPF genes were not associated with an increased risk of OSCC. Gene-environment interactions with smoking were not significant for any polymorphism. The presence of polymorphic variants of the XPD gene in association with alcohol consumption conferred an increased risk of 1.86 (95% CI: 0.86 – 4.01, p=0.03) for OSCC. Only APEX1 was associated with decreased specific survival (HR 3.94, 95% CI: 1.31 – 11.88, p=0.01). These results suggest an interaction between polymorphic variants of the XPF gene and alcohol consumption. Additionally APEX1 may represent a prognostic marker for OSCC.

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Faults in the genes responsible for repairs to the DNA can influence the onset of cancer or affect the response to treatment. This research evaluated the frequency of three single nucleotide polymorphisms (SNPs) in two repair genes DNA RAD51 172g> T (rs1801321), RAD51 135G> C (rs1801320) and XRCC3 T241M (rs861539) in individuals without cancer (n = 130) and patients with oral squamous cell carcinoma (OSC) and carcinoma oropharyngeal squamous (ORSC) (n = 126) and investigated possible relationships of these findings with clinical and pathological data and clinical outcomes: tumor response to radiotherapy and chemotherapy, disease-free survival, and overall survival. It was found that the allele and genotype frequencies were in equilibrium Hard-Weinberg equilibrium. The presence of at least one polymorphic allele in XRCC3 (rs861539) gene is associated with histological grade (WHO) higher (p = 0.007). We observed a higher recurrence rate trend (p = 0.08) and more advanced stage (p = 0.08) in the group that had at least one polymorphic allele of RAD51 gene (rs1801321). The presence of the analyzed SNPs not proved to be a risk factor for the development of CEO or CEOR; however, when combined with smoking or drinking, increased the risk of developing cancer from three to one hundred and fifty times. The tumor response to radiotherapy and chemotherapy was similar in patients with and without SNPs. No polymorphism showed statistical significance in relation to recurrence-free survival or overall survival. We conclude that the presence of at least one polymorphic allele of the SNPs rs861539 in XRCC3 gene, rs1801320 and rs1801321 in the RAD51 gene increase the risk of development of OSC and ORSC, when associated with the habit of drinking or smoking. Polymorphisms studied in XRCC3 and RAD51 genes are not associated with response to radiation therapy, relapse-free survival or overall survival.

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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.

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The aim of the present study was to analyze cardiovascular risk of women with a history of preeclampsia, as well as its follow-upin the National Health System.This is a cross-sectional quantitative research conducted at the Januário Cicco Maternity School. The study population was composed of 573 women selected from a databank belonging to the Women s Health Research Group of the Gynecology Department at Universidade Federal do Rio Grande do Norte, with a history of preeclampsia, and normotensives who gave birth at this institution five years before. The final sample consisted of 147 women, 64 in the group with a history of PE and 83 normotensives. Data were collected on a questionnaire containing the following: sociodemographic aspects, anthropometric measures, life habits, personal and family history of pregnancy-induced hypertension, family history of cardiovascular diseases and frequency of measuring current blood pressure levels. In relation to the association between cardiovascular risk and altered blood pressure (≥130x85 mmHg), the likelihood of exhibiting the latter condition was significantly higher in women with a history of preeclampsia (CI 95% 4.12-38.92), the overweight and obese (CI 95% 1.70-20.75), and in those with a family historyof CVD and personal history of PIH (CI 95% 0.78-47.07 and CI 95% 3.20-25.39) respectively. Likewise, the probability of having altered blood pressure was higher in women with fasting glycemia ≥100mg/dL (CI 95% 2.09-24.73), as well as in those with triglycerides ≥150mg/dl (CI 95% 1.72-9.66). After fitting the logistic model, diagnosis previous preeclampsia and altered triglycerides remained as explanatory variables.The women with a history of preeclampsia five years before exhibited altered blood pressure levels, clinical and laboratory manifestations suggestive of elevated risk for cardiovascular disease, as well as family and personal history of hypertension. There is no differential treatment or adequate outpatient follow-up for this population in basic health care units

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Existem fortes evidências de que os programas de rastreamento baseados em citologia resultaram em diminuição significativa da incidência e mortalidade por câncer do colo do útero, no entanto, um excesso substancial de tratamento de lesões intraepiteliais de baixo grau que dificilmente progrediriam para carcinoma cervical resulta da baixa especificidade do tradicional rastreio citológico. A detecção precoce das lesões através do rastreamento citológico e a avaliação do grau histológico em espécimes cervicais são fundamentais, entretanto não permitem identificar quais pacientes terão maior probabilidade de progressão para lesões de alto grau e carcinoma invasivo. A busca de potenciais marcadores de prognóstico; objetivando o entendimento da progressão das lesões intraepiteliais é de suma importância. Acredita-se que fatores imunoregulatórios, imunogenéticos e proteínas do ciclo celular estejam intimamente envolvidos no processo de carcinogênese. Considerando o exposto, a proposta do projeto foi inicialmente avaliar a eficácia da citologia oncológica no rastreamento do câncer cervical, foi investigado ainda o polimorfismo do gene do fator de transcrição FOXP3 e a expressão da proteína do ciclo celular P63 (P63) associados respectivamente a diagnóstico e prognóstico das lesões cervicais. Em um primeiro momento foi realizado estudo transversal que envolveu 3194 mulheres. As participantes foram submetidas à citologia e biópsia de colo dirigida por colposcopia e os resultados foram comparados para verificar-se a acurácia do teste de Papanicolaou na detecção de lesões intraepiteliais e câncer cervical. Posteriormente, realizou-se estudo comparativo do tipo observacional estratificado em três grupos: Grupo 1: 16 casos com diagnóstico histopatológico de metaplasia/cervicite, considerados normais, Grupo 2: 11 casos com lesão de baixo grau (LSIL) e Grupo 3: 15 casos com lesão de alto grau (HSIL) ou carcinoma epidermoide de colo. Um total de 42 participantes respondeu a um questionário epidemiológico padronizado sobre as características demográficas, hábitos pregressos, história reprodutiva e de comportamento sexual. Após exame colposcópico, foram coletados fragmentos de espécimes cervicais para a pesquisa da expressão proteica da P63 por imunohistoquímica. Amostras de sangue periférico foram coletadas para extração do DNA e detecção do polimorfismo do gene FOXP3. No primeiro estudo em que se avaliou a acurácia do teste de Papanicolaou, encontrou-se sensibilidade de 0,83, valor preditivo positivo (VPP) de 0,77 e especificidade de 0,23 no rastreamento das lesões cervicais e câncer de colo. viii Melhores resultados foram observados quando se avaliou a acurácia diagnóstica para lesões de alto grau e carcinoma com VPP de 0,99 e especificidade de 0,84.No estudo subsequente onde se comparou a expressão da proteína P63 observou-se maior número de núcleos marcados no grupo com lesões intraepiteliais de alto grau e câncer quando comparado ao grupo com biópsias negativas (p=0,0004). No último estudo pesquisou-se a associação do polimorfismo do gene FOXP3 com lesões intraepiteliais cervicais sendo evidenciada maior prevalência do genótipo heterozigoto, CT, no grupo com lesões de colo na histopatologia (p=0,027). Mulheres com lesões intraepiteliais de baixo ou alto grau e câncer de colo de útero apresentam maior expressão da proteína P63 e maior prevalência de genótipo heterozigoto do gene FOXP3 em comparação com as sem lesões cervicais. A associação da pesquisa da expressão da proteína e do polimorfismo do gene pode tornar os exames utilizados atualmente para a avaliação diagnóstica e prognóstica das lesões de colo uterino mais efetivos em detectar quais as mulheres com maior risco para progressão para câncer

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

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The work has objective to present actions of Physiotherapy, developed by SUS in the State of Rio Grande do Norte; discuss under the humanization point of view such actions of health; discuss the importance of physioterapy to the Norte-Riograndense, or maybe its role in the perpetuation of actions of health centered in the binomial cause/efect. The study was done in the State of Rio Grande do Norte. The data were obtained through public sources gathered in the health secretrary ship of this State. The collected data talks about physiotherapy sections developed by SUS in several areas of the State; such data was collected and analysed after the aproval of Ethic and Resarch Committee of Federal University of Rio Grande do Norte. Concerning the physiotherapy, along with the State Health Secretaryship of the State fo Rio Grande do Norte, there were only records of attending based on cure/rehabillitation, not being observed during the curse of study, any record or action of prevention, promotion and protection towards health. It s possible to notice that there is a highligth to the interventions focusing on the treatment of illness of rheumatic origin and general complaints related to the vertebral column. Such research evidenced that the Physiotherapy in the SUS in the State priorizes the individualized attending centered in the carteziano health/illness model, where the developde actions are turned to the curative and rehabilliting attention, with role fo some or no highligth in the primary attention

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This work has a study object the main thinking work of Johan Kaspar Schmidt well known as Max Stirner (1806-1856) - originally titled (in German), Der Einzige und sein Eigentun, and translated into Portuguese by the Portuguese publisher Antígona in 2004, under the title The Unique and its Ownership. This book was known in 1844 although its publication dated 1845 seen that the censor of that time rejected the publication request in that year - saying that ( ) in concrete passages of that work, not only God, Christ, the church and the religion are usually object of proposal blasphemy, but also because all social order, the state and the government are defined as something that should not exist simultaneously as one justifies the lie, perjury, the murder and suicide and denies the ownership right. After this first attack and rejection by its bearing the unique come to be others target, due practically to all the philosophical political thinkers its time including thinkers like Ludwig Feuerbach and Karl Marx & Friedrich Engels in spite of, on the other hand, having inspired formulations and reformulations of many of those thinkers that were against then in their times, as well as those thinkers that came after then such as Nietzsche himself. Even though this work was be victim of powerful attempts of erasing it of history, it has shown a great repercussion power and that is the main reason that led us to ask the following questions what is its big originality? , how could his author arrive at a so impactant perspective? What is its most legitimate political place? We endeavored in elaborate answers to those questions trough the exegesis of its text, taking in account both the scholarship environment where the author produced his intellectual life set - and the detailed reading of texts linked to discussion in focus, where this reading is always based upon the meaning and senses traced by the texts and its contexts as a precaution against the limits and the traps of the readings which shed light markedly on strict letter of the phrases constructs. Ours conclusions point at to the idea that a work like this , that subverts the characteristic ways of thought of the modernity, completely, continues being a utter odds, without rank in the history of thought and the moderns political practices, finding parallel possibility only, in a very special way, with a certain autharchic perspective of Ancient Greece

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This research aims to analyze, in the view of students, the pedagogic project of undergraduate nursing course, of UFRN, and its articulation with the SUS, in an attempt to understand the issues that permeate the teaching and learning of nursing. This is a qualitative study that used the focus group technique as a tool to collect empirical data. There were three meetings, where we had the collaboration of 23 graduating students from the eighth period of the semester 2009.1. For the analysis of information, we use a theoretical framework based on curriculum guidelines and basic principles of the SUS, making the analogy of the results with the metaphor of Greek mythology, Ariadne's thread, in dialogue with authors who discuss education as a transformative practice. Thus, the texture of the yarn was built of five thematic fields: joint the pedagogic project with the SUS; the teaching/service and theory/practice relation; interdisciplinarity or transdisciplinarity; didactic/methodological and relational approaches; and co-participation of students in the pedagogic project. According to the discussions, we find many difficulties in the teaching and learning process of undergraduate nursing in UFRN to strengthen the SUS, including: dislocation of educational institutions with services, professionals, managers and community; dichotomy between theory and practice; reality of services as a learning field and working process in health; posture adopted by professionals, teachers and other subjects included in the process of health education; decontextualization and fragmentation of teaching with the practice in health and nursing; excessive use of very illustrative methodologies, but little problem-solving; difficult and precarious situation in the relations between teachers and between teachers/students, regarding the acceptance of differences; absence of participation of students in the evaluation process and conduct of the educational project in progress. In this sense, we understand the need an auto-reflexive act of teaching and conducting collective pedagogical course with a view to achieving the SUS. Thus, it is necessary to support practices motivated by the polyphonic dialogue and the exercise of symbiosis and autopoiesis of subjects/actors jointly responsible for the ongoing process of learning for life.

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One of the Ministry of Health s attempts at contributing to making collective health more appealing to health students is the Experience and In-Service Training within the Reality of the Unified Health Service Project (VER-SUS). Hence, the object of this investigation is to survey learners views on the teaching of nursing based in the experiences they have lived through in the VER-SUS. Its purpose is to analyze the views and lived-through experiences of nursing students on how the VER-SUS contributed to their professional education. This is a study of the descriptiveexploratory type with a qualitative approach. Eighteen undergraduate students from the nursing program at the Federal University of Rio Grande do Norte (UFRN), former VER-SUS participants, took part in this study, from 2006 to 2009. Information was collected using focus group techniques guided by a set of questions and semistructured interview with open and closed questions. The information collected was analyzed using content analysis technique, of the thematic analysis type. The UFRN Research Ethics Committee approved of the survey pursuant to Report Opinion number 223/2010 and CAAE number 0105.0.051.000-10. Lived-through experiences and in-service training gathered from the VER-SUS have contributed meaningfully to health education, as they helped understand the role of the university and of a health and nursing education within the hegemonic model of education. According to the views and lived-through experiences of nursing students who took part in the SUS project it was extremely relevant to use active methodologies in the teaching-learning process and have the facilitators act as liaisons for the SUS. It follows from this study that the VER-SUS does contribute to a health-nursing education and brings the students close to the reality of the community

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The number of applications based on embedded systems grows significantly every year, even with the fact that embedded systems have restrictions, and simple processing units, the performance of these has improved every day. However the complexity of applications also increase, a better performance will always be necessary. So even such advances, there are cases, which an embedded system with a single unit of processing is not sufficient to achieve the information processing in real time. To improve the performance of these systems, an implementation with parallel processing can be used in more complex applications that require high performance. The idea is to move beyond applications that already use embedded systems, exploring the use of a set of units processing working together to implement an intelligent algorithm. The number of existing works in the areas of parallel processing, systems intelligent and embedded systems is wide. However works that link these three areas to solve any problem are reduced. In this context, this work aimed to use tools available for FPGA architectures, to develop a platform with multiple processors to use in pattern classification with artificial neural networks

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The phylogeny is one of the main activities of the modern taxonomists and a way to reconstruct the history of the life through comparative analysis of these sequences stored in their genomes aimed find any justification for the origin or evolution of them. Among the sequences with a high level of conservation are the genes of repair because it is important for the conservation and maintenance of genetic stability. Hence, variations in repair genes, as the genes of the nucleotide excision repair (NER), may indicate a possible gene transfer between species. This study aimed to examine the evolutionary history of the components of the NER. For this, sequences of UVRA, UVRB, UVRC and XPB were obtained from GenBank by Blast-p, considering 10-15 as cutoff to create a database. Phylogenetic studies were done using algorithms in PAUP programs, BAYES and PHYLIP package. Phylogenetic trees were build with protein sequences and with sequences of 16S ribosomal RNA for comparative analysis by the methods of parsimony, likelihood and Bayesian. The XPB tree shows that archaeal´s XPB helicases are similar to eukaryotic helicases. According to this data, we infer that the eukaryote nucleotide excision repair system had appeared in Archaea. At UVRA, UVRB and UVRC trees was found a monophyletic group formed by three species of epsilonproteobacterias class, three species of mollicutes class and archaeabacterias of Methanobacteria and Methanococci classes. This information is supported by a tree obtained with the proteins, UVRA, UVRB and UVRC concatenated. Thus, although there are arguments in the literature defending the horizontal transfer of the system uvrABC of bacteria to archaeabacterias, the analysis made in this study suggests that occurred a vertical transfer, from archaeabacteria, of both the NER genes: uvrABC and XPs. According the parsimony, this is the best way because of the occurrence of monophyletic groups, the time of divergence of classes and number of archaeabacterias species with uvrABC system

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This work shows the professional staff of the Family Health Program (PSF) in Santana do Matos City perceive the Unified Health System (SUS). Their discourse and recognition of the advances of SUS, as well as their participation on the implementation of the system, are analyzed. The Brazilian Ministry of Health instituted it in 1994 in order to rebuild the health politics on a new basis, substituting the traditional model. The city-centered implementation of SUS was instituted on May 27, 1992 by the act nº 631/92 and today it experiences a Full Management of Basic Attention. In July 2001 the PSF program was started in the city with 5 teams: 2 in the urban zone and 3 in the rural one. The methodology was developed with the combination of qualitative and quantitative research with the employment of a questionnaire with both open and closed inquiries to 31 members of the program. The study appointed that, no matter how positive and enlarged be the staff s concept of health and SUS, they dont s have on understanding of the total chain of the system on its integrality, hierarchy and regionality what hinders the system performance close to the users. The PSF incorporates and reaffirms the basic principles of the SUS; however, on its everyday employment it has not yet abandoned totally the curative model, which is reinforced by the hospital-centered and physiscian-centerend culture