Estudos de microsatélites em humanos: aplicações na identificação de indivíduos, genética de populações, datação de mutações e diagnóstico de doenças

Os microsatélites, também chamados STRs (Short Tandem Repeat), são pequenas sequências de DNA que consistem numa sequência de repetições de um motivo que varia de um a seis pares de bases. Existem em quase todos os cromossomas humanos e podem situar-se nos exões ou nos intrões. Estes últimos são altamente polimórficos e são por isso utilizados na identificação de indivíduos em testes de paternidade e também em estudos de genética de populações. A combinação dos vários genótipos possíveis faz com que cada indivíduo possua um perfil único, que permite a sua identificação. Existem também microsatélites associados a exões ou a regiões promotoras dos genes, normalmente repetições trinucleotídicas CGG/CCG ou CAG/CTG, associados a doenças neurodegenerativas como a síndrome do X-frágil e a doença de Huntington. Neste trabalho caracterizaram-se geneticamente várias populações humanas dos arquipélagos da Madeira, Açores e Cabo Verde. A partir do estudo dos microsatélites do cromossoma Y, foram definidas idades de coalescência que permitiram concluir que as cópias do gene DAZ situado no cromossoma Y são o resultado de um processo evolutivo estando a sua evolução associada a alguns haplogrupos. Verificou-se também a ocorrência de possíveis mutações nos SNPs que definem os haplogrupos, através da comparação dos microsatélites do cromossoma Y dentro de cada haplogrupo, especialmente no haplogrupo E3b. Verificou-se existir uma associação entre o número de repetições CAG e GGC do gene Receptor de Androgénios (AR), situado no cromossoma X, e a infertilidade especialmente quando combinados os dois polimorfismos, parecendo haver um efeito protector dos alelos maiores e alguma susceptibilidade para os alelos menores. Quando se estudou o número de repetições GGC do gene FMR1 em doentes com suspeita de síndrome de X-frágil observaram-se diferenças significativas quando comparadas com a população em geral e com um grupo de sobredotados. Essa diferença deveu-se principalmente à presença do alelo 29 em quase todos os indivíduos do primeiro grupo o que por si só não constitui um factor de risco mas poderá ser uma indicação da associação deste alelo com outra mutação no mesmo gene que possa ser responsável por este fenótipo.

Avaliação do perfil urinário de biomarcadores do stress oxidativo e a sua correlação com as doenças cardiovasculares

Com a realização deste trabalho pretendeu-se estabelecer o perfil urinário de níveis de biomarcadores do stress oxidativo (5-HMU; UAc; MDA; 8-OHdG) em indivíduos saudáveis (grupo controlo) comparando com o de doenças cardiovasculares (grupo CVD) de modo a avaliar o seu potencial como possíveis biomarcadores da possibilidade de ocorrência de CVD. A extração dos compostos alvos foi realizada por recurso a uma nova técnica extrativa - microextração com adsorvente empacotado em seringa (MEPS) controlada digitalmente (eVol). A análise dos biomarcadores foi efetuada por cromatografia líquida de ultra eficiência (UHPLC) utilizando como coluna analítica a HSS T3 (100 mm × 2,1 mm, 1,7 μm de tamanho da partícula) e com um sistema deteção de fotodiodos (PDA). Otimizaram-se os parâmetros experimentais com influência no processo extrativo, nomeadamente no que se refere ao tipo de adsorvente, á influência do pH, ao volume de amostra, ao número de ciclos extrativos, lavagem e ao volume de eluição. Foram ensaiadas diferentes condições experimentais e selecionadas as que corresponderam a uma maior eficiência extrativa, expressa pela área total relativa dos analitos e reprodutibilidade. Os melhores resultados foram obtidos usando como adsorvente C8, o pH da amostra ajustado a 6, o adsorvente foi carregado com 5x50 μL de amostra e a eluição com 1x50 μL de 0,01% ácido formico e 3x50 μL de 20% metanol. Para a separação cromatográfica dos analitos usou-se uma fase móvel binária (0,01% ácido fórmico:20% metanol), em modo isocrático e um fluxo de 250 μL min-1. O método analítico foi validado em termos de seletividade, linearidade, limite de deteção (LOD), limite de quantificação (LOQ), efeito matriz, exatidão e precisão (intra e interdias) e aplicada a determinação de biomarcadores alvo nos dois grupos estudados, obtiveram-se bons resultados em termos seletividade e linearidade (R2>0,9906), os valores de LOD e LOQ obtidos foram baixos, variando entre 0,00005 - 0,72 μg mL-1 e 0,00023 – 2,31 μg mL-1 respetivamente. Os resultados da percentagem de recuperação (91,06 – 123,02 %), precisão intra-dia (0,95 – 8,34 %), precisão inter-dia (4,58 -6,33 %) e o efeito de matriz (60,11 – 110,29 %) deste método foram satisfatórios. A aplicação da metodologia validada aos dois grupos em estudo permitiu concluir que as concentrações de UAc e MDA entre os dois grupos, contrariamente ao 5-HMU e ao 8- OhdG cujas concentrações são estatisticamente diferentes entre o grupo controlam e o grupo CVD.

Análise do estado da arte dos aspectos diagnóticos, periciais e jurisprudenciais das LER/DORT no contexto previdenciário das doenças do trabalho no Brasil

Objetivo: analisar o estado da arte dos aspectos diagnósticos, periciais e jurisprudenciais das LER/DORT (Lesões por Esforços Repetitivos / Distúrbios Osteomusculares Relacionados ao Trabalho) no Brasil. Materiais e Método: trata-se de pesquisa descritiva, de natureza qualitativa, com formato documental, utilizando-se a técnica de análise de conteúdo. A avaliação evolutiva da legislação previdenciária relacionada as LER/DORT foi realizada através da pesquisa no banco de dados disponibilizado pelo Governo Federal e mediante a consulta ao DATAPREV/Sislex. A avaliação dos aspectos diagnósticos foi instrumentalizada através, principalmente, de artigos científicos publicados entre 2003 e 2008, nas línguas portuguesa, inglesa, espanhola e francesa, relacionados com os métodos de diagnósticos complementares das LER-DORT (ressonância magnética, tomografia computadorizada, ultrassonografia e eletroneuromiografia). As jurisprudências foram obtidas através da busca dos julgados sobre o tema, entre 2003 e 2008, pertencentes ao Supremo Tribunal Federal, Superior Tribunal de Justiça, Tribunais Regionais Federais, Tribunal Superior do Trabalho e Tribunais Regionais do Trabalho. Resultados: foram identificados 48 artigos abordando os aspectos diagnósticos das LER-DORT, observando-se que os exames por ressonância magnética, ultrassonografia e eletromiografia demonstraram ser mais efetivos, dentro das suas especificidades, para a complementação do exame clínico de patologias relacionadas às LER-DORT. A análise das 123 jurisprudências selecionadas demonstrou, de forma geral, que as LER-DORT equiparam-se ao acidente de trabalho, devendo apresentar nexo de causalidade (atestado através de laudo médico-pericial) e, ainda, ensejam a ação por danos morais, a qual, devido à EC nº 45 passou a ser competência da Justiça do Trabalho. O Estado da arte dos aspectos periciais encontra-se representado pela vigência da Instrução Normativa n. 98/2003, a qual traz como aspecto fundamental a determinação de novos parâmetros a serem considerados na definição de um quadro de LER-DORT, dispondo, ainda, sobre a conduta ética que deve ser adotada pelo médico perito, bem como chama a atenção para a necessidade dessas doenças do trabalho serem comunicadas às autoridadades competentes, através da emissão da Comunicação de Acidente de Trabalho (CAT). Conclusão: as LER-DORT representam, hoje, um problema de importante impacto, não apenas previdenciário, mas também econômico em diversos países, nos quais o Brasil encontra-se inserido. Estudos sobre o estado da arte relacionados às LER-DORT são fundamentais para auxiliar na construção de um modelo crítico e consciente que colabore com a garantia de sustentabilidade do sistema previdenciário no Brasil

Sistemas de informação geográfica e análise espacial de dados como ferramentas para determinação de agregação espacial de doenças: a hanseníase como modelo

This work demonstrates the importance of using tools used in geographic information systems (GIS) and spatial data analysis (SDA) for the study of infectious diseases. Analysis methods were used to describe more fully the spatial distribution of a particular disease by incorporating the geographical element in the analysis. In Chapter 1, we report the historical evolution of these techniques in the field of human health and use Hansen s disease (leprosy) in Rio Grande do Norte as an example. In Chapter 2, we introduced a few basic theoretical concepts on the methodology and classified the types of spatial data commonly treated. Chapters 3 and 4 defined and demonstrated the use of the two most important techniques for analysis of health data, which are data point processes and data area. We modelled the case distribution of Hansen s disease in the city of Mossoró - RN. In the analysis, we used R scripts and made available routines and analitical procedures developed by the author. This approach can be easily used by researchers in several areas. As practical results, major risk areas in Mossoró leprosy were detected, and its association with the socioeconomic profile of the population at risk was found. Moreover, it is clearly shown that his approach could be of great help to be used continuously in data analysis and processing, allowing the development of new strategies to work might increase the use of such techniques in data analysis in health care

Avaliação dos parâmetros hematológicos e imunofenotípicos de pacientes com doenças linfoproliferativas crônicas no Rio Grande do Norte

Chronic lymphoproliferative disorders (DLPC) are lymphoid system diseases characterized by the abnormal proliferation of mature lymphocytes that affect B cells, T lymphocytes and NK cells. The aim of the study was to demonstrate the relevance of immunophenotyping by flow cytometry in patients with prolonged lymphocytosis and / or cytomorphological changes compatible with lymphoproliferative diseases. In this study 460 patients (244 men and 216 women) with DLPC were evaluated. Were analyzed by flow cytometry with a panel of monoclonal antibodies consisting of CD3, CD4, CD5, CD8, CD10, CD19, CD22, CD23, CD25, CD38, CD45, CD16/CD56, and HLADR heavy and light chains of immunoglobulins. It also examines information regarding age, gender of patients and laboratory data as leucocytes, cytomorphological analysis, platelet count and hemoglobin determination. The results showed 398 cases of chronic lymphoproliferative disorders and 62 of DLPC B cell lymphoproliferative diseases T. B showed the following distribution : 253 cases of chronic lymphocytic leukemia (CLL), 42 cases of multiple myeloma ( MM ), 37 cases of lymphoma non - Hodgkin lymphoma in leukemic phase (NHL) , 17 cases of pro- B lymphocytic leukemia ( B -PLL), 15 cases of mantle cell lymphoma (MCL ), 12 cases of plasma cell leukemia ( PCL), 9 cases of lymphoma Burkitt (Linf B), 8 cases of leukemia villous cells ( LCV), 3 cases of splenic lymphoma with villous cells (LECV), a case of follicular lymphoma (LF) and a Waldenströn macroglobulinemia ( MW). The diseases source NK / T were 23 cases of peripheral T cell lymphoma (LCTP), 14 cases of T prolymphocytic leukemia (T -PLL), 10 cases of leukemia T of large granular lymphocytes (LGL -T) 9 cases of leukemia cells of adult T (LCTA), 5 cases of Sezary syndrome (SS) and a case of large granular NK leukemia (LGL -NK) lymphocytes. In conclusion, the combined use of the monoclonal antibody panel careful cytomorphological analysis was shown to be essential in immune diagnosis and classification of chronic lymphoproliferative disorders. This study was approved by the IRB - HUOL under number 356 / 09

Serviço de atendimento móvel de urgência (SAMU) e a assistência às urgências psiquiátricas

The objective of this work which is characterized as an applied research, with a qualitative exploratory approach and has case study character has been the analysis of the conceptions and dealings of health professionals of SAMU in Natal RN about the attendance of psychiatric urgencies. The information was collected between the months of March and April of 2010, by means of semi-structured interviews, performed with 24 health professionals integrating of SAMU-Natal as well as the usage of direct observation technique, performed in the institution's medical regulation room. Both the number of professionals involved in the interviews and the bringing about of the observations, were determined by saturation methods in qualitative research's information collecting. The interviews and observations were transcribed and submitted to contents analysis technique , more specifically, to thematic analysis, which made possible to reach the deepest levels, that go beyond what has simply been manifest in the speech of the interviewed, getting to the relations among the categories and social structures of the issue of the research. Keeping this in mind, three analysis categories have been built, namely: conceptions and concepts of psychiatric urgencies shared by health professionals in SAMU-Natal; attendances to psychiatric urgencies in SAMU-Natal; and the Brazilian Psychiatric Reformation under the view of the SAMU-Natal's health professionals. Reflection about the analyzed information revealed discussions pertaining to the stigma and prejudice on mental illness, and also, pointed out to some hindrances which impair the attendance to individuals in mental suffering in SAMU-Natal. The interviewed health professionals' conceptions on the individual in psychical crisis involve concepts of unpredictability, aggressiveness and risk, stigmatizing elements and historically associated to the social hazard ideology and need for mentally sicks' segregation. The predominance of these conceptions, seen in health professionals speech, had identifiable reflexes on assistance to psychiatric demands performed by SAMU-Natal, namely: indiscriminate request for military police's presence during psychic crisis intervention, neglect about occasions that involve mental health patients, as well as repetitive assisting practice directed on physical contention, and transportation to psychiatric hospital. Associated to it, the professionals have shown distorted and reductionist understanding about Brazilian Psychiatric Reformation, and, in the majority, haven't lent credibility to present model of attention to mental health, based on psycho-social treatment, pointing their speech to a need for psychiatric patient's internment. In this sense, we notice that the hospital-centered and excluding model conceived by classical psychiatry still remains alive in these health professionals' mentality as a reference to psychiatric urgency's assistance. Therefore, the research revealed a sequence of elements, that make us think about the challenges that health sector and society must face to realize Brazilian Psychiatric Reformation's principles and guidelines

Reinternações psiquiátricas no Rio Grande do Norte: implicações e impacto das novas estratégias de atenção à saúde mental

The Brazilian Psychiatric Reform based on the desinstitucionalization of the assistance, translated to the emphasis on community/territorial treatment and in the social inclusion of the mental suffering, promoted advances in the psychiatric restructuring. In the Rio Grande do Norte (RN), we can enumerate as advances of the Brazilian Psychiatric Reform the expansion of the mental health care chain and the implementation of some strategies that, together, aims to further the psychosocial attention of the individual with psych suffering and to reduce the indices of psychiatrics readmissions in the state. In the current Brazilian‟s mental health situation we were interesting in answered the following question: what the impact of the substitutes services‟ extension in the revolving door phenomenon? This search aims to analyze the revolving door phenomenon occurrences based on the news strategies of mental health care in the Rio Grande do Norte. This is a descriptive-exploratory study with a qualitative approach, oriented by the theoretical framework of critical-dialectical approach about the Brazilian Psychiatric Reform and using the thematic oral history as method of information collects. The search was realized on the Hospital João Machado (HJM), estate reference in psychiatric treatment, and the participants was 20 professionals that work on it. The collection of information had started after the approval of the UFRN Research Ethics Committee with the opinion number 216/2011 and CAAE number 0021.0.051.000-11 and was realized using the direct observation and semi-structured interview. The study‟s results were categorized in two categories and five subcategories of analysis. CATEGORY 1) Current situation of the mental health care chain in the RN, with the subcategories: 1.1 Impact of the new services of mental health care in the revolving door phenomenon in the RN; 1.2 Implications of the new services of mental health care in assisting user to the HJM; 1.3 Issues the permeate the mental health care chain in the RN. CATEORY 2) Main causes of the revolving door phenomenon in HJM, with the categories: 2.1 Family problems; 2.2 Lack of assistance after discharge from psychiatric hospital. In summary, we conclude that the extension of the mental health care chain contributed for the reduction of the psychiatrics re-hospitalization‟s indices in RN. However, we realized that territorial services of mental health care are not the only responsible for the revolving door phenomenon. Factors as family problems and the disarticulation of the assistance after the discharge from hospital influence on the perpetuation of hospitalizations and re-hospitalizations in the local scenario. To study the revolving door phenomenon that occur in the psychiatrics‟ assistance considering the news strategies of mental health care allowed us to approach the advances and challenges brought by the RPb and by the desinstitucionatization in the state, indicating the need for further discussions and problem-solving strategies of psychosocial care.

Atuação do enfermeiro na estratégia de atenção integrada às doenças prevalentes na infância

This study aimed to describe nurses' actions in the strategy of Integrated Management of Childhood Illness in the city of Natal, Rio Grande do Norte. This is a qualitative study with descriptive approach. The universe consisted of nurses from the Family Health Strategy, totaling 16 participants. For the research project was submitted for approval by the Ethics Committee of the Universidade Federal do Rio Grande do Norte, obtaining Opinion No. 187/2012. Data were obtained in two ways: a questionnaire survey to profile the training of nurses and an interview guided by a structured interview. Interviews were treated in the light of analysis of thematic category Bardin. The results showed the central thematic study "Integrated Management of Childhood Illness in the context of nursing activities" category and three analyzes: "Understanding the Integrated Management of Childhood Illness", "Difficulties invibializam use IMCI "and" Working conditions for nurses in the Integrated Management of Childhood Illness. " It is observed that nurses consider the Integrated Management of Childhood Illness useful, effective and important to keep sick children within the logic curative. However disregard the character of health promotion and disease prevention thereof. It was found that the participants still hold the attendance of crinaças within the biomedical model and that these same professionals are subjected to increasingly precarious working conditions and unhealthy due to lack of human and material resources. It was found that the interviewees do not follow the protocols of strategy because of barriers related to prescription medications by nurses, the medical, the lack of incentives, training and supervision by the municipal health and the Regional Nursing Council

Trajetos no labirinto: história de vida dos portadores de doenças oncológicas em uso de transfusões sanguíneas na cidade de Natal/RN

The studies paths in the maze: life story of individuals with oncological diseases into use of blood transfusion in Natal has the hemotherapy as a primordial procedure to review the relationship between users of oncological health and the due ramifications. The hemotherapy looks for supply the organic needs through blood transfusion, which acquires vital function to the ones that have cancer, because it might reestablish the functionality of the organism throughout the raising of blood components. The impact over the transfusion affects emotionally and physically the users life. Aiming to reflect on these impacts, this study tried, through narratives of lives, rescue their experience since their knowledge of the disease until the time of blood transfusion using. It s about an exploratory-descriptive study, where the qualitative approach uses the theoretical-methodological reference of the oral life history to analyze a colony consisting of five users of health diagnosed with cancer, with achievement of at least three blood transfusions, the clinic Núcleo de Hematologia e Hemoterapia - UFRN, in Natal-RN. The network, in turn, was composed by employees of both sexes, regardless of age, who voluntarily agreed to participate in the study. The data collection, with approval of the Ethics Committee in Research, Liga Norte Riograndense Contra o Cancer, on the number 001/001/2012, occurred through semi-structured interviews, recorded individually in the home context that was previously chosen by employees. The methodological procedure occurred with the transcription of the interviews and their transcreations, and analysis of reports by thematic content analysis. At the reading orientation and interpretation of the employees stories, were discussed three categories of analysis: the impact on psychological REVIEW; impact on socialization and group membership, the environment and the impact of blood transfusion on treatment. Based on the narrative of the life histories of employees, we conclude that the experiences and feelings, hope and sorrow, pain and faith, even when facing a disease like cancer, bring lots of teaching and learning to health professional that deposits humanization health and reinstate hemotherapy forms of clinical critical

Assistência de enfermagem às urgências e emergências psiquiátricas no serviço de atendimento móvel de urgência em Mossoró-RN

This study aims to identify the concepts of professional nursing team on assistance in urgency and psychiatric emergencies in SAMU in Mossoró/RN, identifying the difficulties in implementing an emergency assistance to the user in psychiatric distress in this service and point strategies in pursuit of consolidation and expansion of comprehensive health care to the public. It is a descriptive research with qualitative and exploratory approach. The subjects were employees of the nursing staff of SAMU of that mentioned municipality. Semi-structured interviews are applied as tool for data collection. It was counted on the consent of the institution where the study was developed and approval by the Ethics Committee in Research of UFRN with CAAE No 17326513.0.0000.5537, besides signing the Informed Free Consent Term by the participants. Data analysis was done by means of thematic analysis proposed by Bardin. Thus , as a result of the research produced the following categories: mechanistic practice; dehumanization of care; need for qualification, barriers to assistance in urgency and psychiatric emergency and strategies in pursuit of comprehensive care, which proceeded in preparing two articles entitled "Nursing care to the emergency room and psychiatric emergencies in the mobile emergency care service" and "Barriers for emergency service and psychiatric emergencies in the mobile emergency care service". In the studied reality it was identified that nursing care offered to users in situations of urgency and psychiatric emergency is made based primarily on the use of chemical and physical restraints, as well as transportation to the general hospital, constantly using the police force support, which meets the guidelines of the Psychiatric Reform and thereby undermining the provision of an effective and humane care. This scenario is worsened by the lack of an organized network of services in mental health, where after the service the user is taken to a general hospital, considering that there is no ready or appropriate psychiatric emergency service as a Center of Psychosocial Care - CAPs III to reference it, thereby precluding the realization of a resolute and comprehensive care. Thus, it is concluded that nursing care is based on biologicist and medicine-centered model advocated by classical psychiatry, and that despite all the advances in psychiatric reform, still guides the mental health care, so the lack of service network organized in hierarchical and mental health, where the user in urgency and emergency service can be watched in full and the guidelines of the psychiatric reform can be realized in practice