Made available in DSpace on 2015-04-14T13:35:39Z (GMT). No. of bitstreams: 1 447914.pdf: 1273209 bytes, checksum: bc6f4a88f17be9566f98a33586d6f9a5 (MD5) Previous issue date: 2013-03-22 / Epilepsy affects 1% of the world population and 30% of these patients are refractory to available medication. Stem cells host hope in the treatment of epilepsy. Given their ability to proliferate, differentiate and production of factors which may activate endogenous mechanisms to restore the injured brain. Knowing that the administration of bone marrow mononuclear cells (BMMC) in animals have therapeutic potential in an experimental model of epilepsy, the aim of this study is to investigate the mechanisms by which administered cells exert their beneficial. In order to better understand the mechanisms of action of transplanted cells, a comparative study was done to detect the expression of trophic factors as brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), nerve growth factor (NGF), transforming growth factor beta (TGF-R) and vascular endothelial growth factor (VEGF) in hippocampi of each experimental groups by ELISA. Experimental model of epilepsy was induced by pilocarpine injection (320 mg/kg; ip). Seizures were scored by Racine s scale. The duration of SE was controlled with diazepan (10mg/kg; ip; 90 minutes after SE onset). Twenty-two days after SE, rats were randomly assigned into groups: Control, Pilo, Pilo+BMMC evaluated in periods 3, 7 and 14 days after transplant. BMMC groups received cell transplantation (obtained from EGFP C57BL/6 mice) via tail vein (1x107 cells, 100L). While control animals received saline instead of pilocarpine. Pilocarpine-treated animals were monitored for the presence of spontaneous seizures for 22 days (7 days prior to cell transplant). Our results showed that there was a change in the protein expression of BDNF, GDNF, NGF, TGF-R and VEGF in the hippocampus of epileptic animals treated with BMMC compared to untreated epileptic animals and control, with variations in the expression of each factor at different times after transplantation. The expression of BDNF, GDNF, NGF and VEGF was high and TGF-R1 reduced after transplantation of BMMC compared to untreated epileptic animals. However, there was no difference in the expression of these factors in untreated epileptic animals compared to control animals, except TGF-R1, which proved to be high in the group of untreated epileptic animals compared to control animals. The results of this study provide additional data on the potential benefit of BMMC as well as provide insight into the mechanism by which BMMC promote functional recovery in epileptic rats. / A epilepsia atinge cerca de 1% da popula??o mundial, sendo que aproximadamente 30% desses pacientes n?o respondem ao tratamento medicamentoso. Por sua vez, as c?lulas-tronco t?m sido consideradas uma esperan?a de tratamento da epilepsia, visto que t?m grande capacidade de prolifera??o, diferencia??o e produ??o de fatores, podendo ativar mecanismos de restaura??o end?gena no c?rebro lesado. Sabendo-se que a administra??o de c?lulas mononucleares da medula ?ssea (CMMO) apresenta potencial terap?utico em um modelo experimental de epilepsia, o objetivo deste estudo ? investigar se o transplante das CMMO em ratos com epilepsia cr?nica modula a express?o de fatores tr?ficos. Com o intuito de melhor compreender os mecanismos de a??o das c?lulas transplantas foi realizada a detec??o da express?o de fatores tr?ficos como o fator neurotr?fico derivado do c?rebro (BDNF), fator neurotr?fico derivado da glia (GDNF), fator de crescimento neural (NGF), fator de crescimento transformador R1 (TGF-R1) e fator de crescimento endotelial vascular (VEGF) em diferentes per?odos ap?s transplante das CMMO nos hipocampos dos grupos experimentais atrav?s da t?cnica de ELISA. A pilocarpina (PILO) foi administrada nos animais (320 mg/kg i.p.,) para indu??o do modelo de epilepsia cr?nica. As crises comportamentais foram classificadas de acordo com a escala de Racine e a dura??o do SE foi controlada com diazepam (10 mg/kg, i.p., 90 minutos). Ap?s 22 dias, o total dos animais foi dividido em grupos: Controle, Pilo e Pilo+CMMO avaliados nos tempos de 3, 7 e 14 dias ap?s o transplante. Os grupos CMMO receberam transplante de c?lulas da camada mononuclear da medula ?ssea, obtidas de camundongos EGFP C57BL/6, via veia caudal (1x107 c?lulas, 100L). Os animais controle receberam solu??o salina nas mesmas condi??es do grupo transplantado. Os animais tratados com pilocarpina foram v?deo-monitorados durante sete dias pr?-transplante para observa??o de crises espont?neas recorrentes (CERs). Nossos resultados mostraram que houve altera??o da express?o proteica de BDNF, GDNF, NGF, TGF-R1 e VEGF nos hipocampos dos animais epil?pticos tratados com as CMMO em rela??o aos animais epil?pticos n?o tratados e controle, havendo varia??es da express?o de cada fator em diferentes tempos ap?s o transplante. A express?o dos fatores BDNF, GDNF, NGF e VEGF mostrou-se elevada e do TGF-R1 reduzida ap?s o transplante das CMMO em rela??o aos animais epil?pticos n?o tratados. Por?m, n?o houve diferen?a na express?o destes fatores nos animais epil?pticos n?o tratados em rela??o aos animais controle, exceto o TGF-R1, o qual se mostrou elevado no grupo de animais epil?pticos n?o tratados em rela??o aos animais controle. Os resultados deste estudo fornecem dados adicionais sobre o benef?cio do potencial das CMMO, bem como fornecer uma vis?o sobre o mecanismo pelo qual as CMMO favorecem a recupera??o funcional em ratos epil?pticos.

Made available in DSpace on 2014-12-17T15:32:18Z (GMT). No. of bitstreams: 1 EmelineNAL.pdf: 2548007 bytes, checksum: d30f88fa3814f13a0bc3ee25b49d05fb (MD5) Previous issue date: 2010-02-18 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Bone marrow transplantation (BMT) is currently the best therapeutic option for patients with hematologic diseases, solid tumors or autoimmune disorders. It is characterized by intravenous infusion of hematopoietic stem cells in order to restore marrow function. However, this procedure requires concomitant immunosuppression treatment, which favors the development of certain complications, often manifested in the oral cavity. This study aimed to evaluate the incidence of oral changes in patients undergoing BMT and to correlate these results with clinical aspects related to the patients and the transplants performed. This is a prevalence study, with cross-sectional design, carried out in a BMT service at the Institute of Onco-Hematology of Natal (ION) and Natal Hospital Center. Data collection was based on questionnaires, clinical examination of the oral cavity and consultation in the medical records. The sample consisted of 51 patients undergoing BMT. After the analysis, was found a general status with good health conditions and presence of oral changes in about half of patients who composed the sample. The manifestations observed were, in decreasing order of frequency: mucositis; gingival alteration and thrombocytopenic purpura; mucosal pigmentation; lichenoid reaction and candidiasis. The oral changes were observed more frequently in cases of allogeneic TMO, in different periods post-transplant, without significant differences related to the source of cells. It was found statistically significant association between the presence of graft-versus-host disease (GVHD) and oral changes (p < 0,001). Therefore, it is concluded that there is a relatively high incidence of changes in oral cavity of patients receiving bone marrow transplantation, a fact which confirms the need to consider this site for examination, diagnosis, treatment and prognosis of possible complications of BMT / O transplante de medula ?ssea (TMO) atualmente constitui a melhor op??o terap?utica para pacientes com doen?as hematol?gicas, tumores s?lidos ou desordens autoimunes. Caracteriza-se pela infus?o intravenosa de c?lulas progenitoras hematopo?ticas com o objetivo de restabelecer a fun??o medular. No entanto, esse procedimento requer tratamento concomitante de imunossupress?o, o que favorece o desenvolvimento de determinadas complica??es, as quais freq?entemente se manifestam na cavidade oral. Este estudo objetivou avaliar a incid?ncia de altera??es orais em pacientes submetidos ao TMO e correlacionar esses resultados com aspectos cl?nicos referentes aos pacientes e aos transplantes realizados. Trata-se de um estudo de preval?ncia, com desenho do tipo seccional, realizado no servi?o de TMO do Instituto de Onco-Hematologia de Natal (ION) e Natal Hospital Center. A coleta de dados baseou-se em aplica??o de question?rio, exame cl?nico da cavidade oral e consulta de informa??es nos prontu?rios m?dicos. A amostra foi constitu?da por 51 pacientes submetidos ao TMO. Ap?s a an?lise, constatou-se quadro geral com boas condi??es de sa?de e presen?a de altera??es orais em aproximadamente metade dos pacientes que compunham a amostra. As manifesta??es observadas foram, em ordem decrescente de frequ?ncia: mucosite; altera??o gengival e p?rpura trombocitop?nica; pigmenta??o da mucosa; rea??o liquen?ide e candid?ase. As altera??es orais foram mais frequentes em casos de TMO alog?nico, em diferentes per?odos p?s-transplantes, sem diferen?a significativa quanto ? origem das c?lulas. Constatou-se associa??o estatisticamente significante entre a presen?a de doen?a do enxerto contra hospedeiro (DECH) e altera??es orais (p < 0,001). Portanto, conclui-se que h? uma incid?ncia relativamente alta de altera??es na cavidade oral de pacientes transplantados de medula ?ssea, fato que confirma a necessidade de se considerar a import?ncia desse s?tio para exame, diagn?stico, tratamento e progn?stico de poss?veis complica??es do TMO

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-03-20T22:18:32Z No. of bitstreams: 1 IsabelleCamposDeAzevedo_DISSERT.pdf: 1420654 bytes, checksum: bdfaecb12b12b0811c4b71d4ba2dfdac (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-03-23T21:22:49Z (GMT) No. of bitstreams: 1 IsabelleCamposDeAzevedo_DISSERT.pdf: 1420654 bytes, checksum: bdfaecb12b12b0811c4b71d4ba2dfdac (MD5) / Made available in DSpace on 2017-03-23T21:22:49Z (GMT). No. of bitstreams: 1 IsabelleCamposDeAzevedo_DISSERT.pdf: 1420654 bytes, checksum: bdfaecb12b12b0811c4b71d4ba2dfdac (MD5) Previous issue date: 2016-12-13 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / O Transplante de C?lulas-Tronco Hematopo?ticas (TCTH) ? utilizado como estrat?gia de tratamento para uma s?rie de agravos malignos e n?o malignos herdados ou adquiridos, com possibilidade de cura ou aumento da sobrevida livre da doen?a. O presente estudo objetivou caracterizar o perfil cl?nico e epidemiol?gico dos pacientes que realizaram TCTH em um servi?o de refer?ncia no estado do Rio Grande do Norte (RN), estimar a sobrevida global dos transplantados e identificar as terapias que favorecem o aumento da sobrevida global. A primeira parte ocorreu junto ao servi?o de refer?ncia do estado do RN para realiza??o do TCTH. Trata de um estudo de abordagem quantitativa, do tipo coorte retrospectiva, descritivo e anal?tico, de base hospitalar que abordou 272 pacientes que realizaram TCTH. Os dados foram coletados no Servi?o de Arquivo M?dico e Estat?stica entre os meses de mar?o e setembro de 2016 por meio dos prontu?rios registrados entre os anos de 2008 e 2015, oito anos de execu??o do procedimento. Para a an?lise descritiva foi utilizado software livre estat?stico R vers?o 3.0.0 e para o c?lculo das probabilidades de sobrevida foi empregado o m?todo Kaplan-Meier por meio do Statistic Package for Social Sciences (SPSS) vers?o 22.0. Para o c?lculo da probabilidade de associa??o entre as caracter?sticas analisadas e os ?bitos foi utilizado o teste do Qui-quadrado de tend?ncia. A segunda parte do estudo se deu pela constru??o de uma Revis?o Sistem?tica (RS) da literatura sobre as terapias que favorecem o aumento a sobrevida de pacientes que realizaram o TCTH. O Protocolo de Pesquisa foi aprovado em seus aspectos ?ticos e metodol?gicos pelo Comit? de ?tica em Pesquisa da Universidade Federal do Rio Grande do Norte, com aprova??o em 01 de julho de 2015, sob o parecer no. 1.132.720 e CAAE no. 46202715.7.0000.5537. Dos 272 prontu?rios analisados houve predom?nio do sexo masculino 52,94%, com m?dia de 38,69 anos, 18,38% eram pardos e 47,06% casados. De acordo com as caracter?sticas cl?nicas, 23,16% apresentou como diagn?stico principal o Mieloma M?ltiplo, as toxicidades mais desenvolvidas foram as gastrointestinais (93,38%), todos os pacientes receberam tratamento por meio de antineopl?sticos, o TCTH realizado com maior frequ?ncia foi o alog?nico (54,78%), com c?lulas do sangue perif?rico (77,94%) e doador aparentado (71,81%). Cerca de 9% dos pacientes realizaram mais de um TCTH, 4,04% desenvolveu a Doen?a do Enxerto Contra Hospedeiro (DECH), dentre estes 54,55% apresentou o tipo cr?nico, a causa de morte mais registrada nas declara??es de ?bito foi o choque s?ptico (48,19%) e a sobrevida global dos pacientes transplantados foi de 4,03 meses, sem diferen?a estatisticamente significativa quando comparados os pacientes de acordo com o sexo (p=0,859). Quanto aos achados da RS n?o foi poss?vel identificar um consenso para definir a melhor forma de tratamento para o favorecimento do aumento da sobrevida global nos estudos revisados. A escolha da terap?utica adequada depender? especialmente das caracter?sticas cl?nicas apresentadas pelos indiv?duos. Entretanto, de forma geral, os planos terap?uticos utilizados pelo bra?o experimento dos ensaios cl?nicos analisados obtiveram melhores respostas para o aumento da sobrevida global dos indiv?duos testados. Portanto, conclui-se que h? a necessidade de realiza??o de outros estudos do tipo multic?ntricos que apresentem os perfis epidemiol?gicos e cl?nicos do TCTH no Brasil, haja vista que estes possibilitam a problematiza??o da realidade e a publica??o de evid?ncias confi?veis para atualiza??o dos conhecimentos cient?ficos. / Hematopoietic stem cell transplantation (HSCT) is used as a treatment strategy for a series of inherited or acquired malignant and non-malignant diseases, with the possibility of cure or increase in disease-free survival. The objective of this study was to characterize the clinical and epidemiological profile of the patients who underwent HSCT at a referral service in the state of Rio Grande do Norte (RN), to estimate the overall survival of transplant recipients and to identify therapies that favor increased overall survival. The first part occurred with the reference service of the state of the RN to perform the HSCT. This is a quantitative, retrospective, descriptive and analytical, hospital-based quantitative study that addressed 272 patients who underwent HSCT. The data were collected in the Medical Record and Statistic Service between March and September 2016 through medical records recorded between the years 2008 and 2015, eight years of execution of the procedure. For the descriptive analysis, statistical free software R version 3.0.0 was used and the Kaplan-Meier method was used to calculate survival probabilities using the Statistic Package for Social Sciences (SPSS) version 22.0. The trend chi-square test was used to calculate the probability of association between the characteristics analyzed and the deaths. The second part of the study was the construction of a Systematic Review (SR) of the literature on the therapies that favor the increase in the survival of patients who underwent HSCT. The Research Protocol was approved in its ethical and methodological aspects by the Research Ethics Committee of the Federal University of Rio Grande do Norte, with approval on July 1, 2015, under no. 1,132,720 and CAAE no. 46202715.7.0000.5537. Of the 272 patient charts analyzed, there was a predominance of males 52.94%, with a mean of 38.69 years, 18.38% were brown and 47.06% married. According to the clinical characteristics, 23.16% had as main diagnosis Multiple Myeloma, the most developed toxicities were gastrointestinal (93.38%), all patients received treatment with antineoplastics, the most frequently performed HSCT was (54.78%) with peripheral blood cells (77.94%) and related donor (71.81%). About 9% of the patients had more than one HSCT, 4.04% developed the Graft versus Host Disease (GVHD), of which 54.55% presented the chronic type, the most registered cause of death in the death certificates was Septic shock (48.19%) and overall survival of transplanted patients was 4.03 months, with no statistically significant difference when patients were compared according to sex (p = 0.859). Regarding the SR findings, it was not possible to identify a consensus to define the best form of treatment to favor the increase in overall survival in the reviewed studies. The choice of appropriate therapy will depend especially on the clinical characteristics presented by individuals. However, in general, the therapeutic plans used by the experimental arm of the analyzed clinical trials obtained better answers to increase the overall survival of the individuals tested. Therefore, it is concluded that there is a need to carry out other multicenter studies that present the epidemiological and clinical profiles of HSCT in Brazil, since these make it possible to problematize reality and to publish reliable evidence to update scientific knowledge.