Made available in DSpace on 2015-04-14T13:35:36Z (GMT). No. of bitstreams: 1 444379.pdf: 796253 bytes, checksum: 4373f9d99666d84dec56318b0fe505a4 (MD5) Previous issue date: 2012-09-14 / Introduction: Lesions hypoxic-ischemic pathologies can cause a higher or lesser degree, depending on when they occur. In postnatal insults, is the common occurrence of scarring, characterizing ulegyria and/or cysts porencephalic (U/PC).Objectives: To associate the location, extent and severity of brain injury in the spectrum U/PC, with characteristics of epilepsy, motor abnormalities and their impact on activities of daily living (ADLs).Methods: We evaluated 21 patients (15 men and 6 women, aged between 15 and 39 years, mean 25.66 SD 7.12) with epilepsy and brain injury by U/PC attending the epilepsy clinic of the Neurology Service S?o Lucas Hospital of the Catholic University of RS. All patients underwent MRI, EEG, motor and functional assessment.Results: Fifteen patients (71%) presented U, 2 (9.8%) PC and 4 (19.2%) U + PC. All EEGs were abnormal, with a predominance of slowing multilobar (66.6%) and multilobar discharges (71%). The vast number of patients (47.6%) had a combination of simple partial seizures (SPS), complex (CPS), evolving to secondarily generalized (GTS). Decreased balance and difficulty in performing activities of daily living were common to 21 patients.Conclusion: motor abnormalities resulting from brain damage, coupled with the occurrence of seizures impact the functional capacity of patients with U/PC / Introdu??o: Les?es hip?xico-isqu?micos (HI) podem causar patologias em maior ou menor grau, dependendo do momento em que estes ocorrem. Em insultos p?s-natais, ? comum a ocorr?ncia de les?es cicatriciais, caracterizando ulegiria e/ou cistos porencef?licos (U/CP).Objetivos: associar a localiza??o, extens?o e gravidade da les?o cerebral no espectro U/CP, com caracter?sticas da epilepsia, das altera??es motoras e do impacto destas em atividades de vida di?ria (AVD).M?todos: Foram avaliados 21 pacientes (15 homens e 6 mulheres, com idades entre 15 e 39 anos, m?dia de 25,66; DP = 7,12) com epilepsia e les?o cerebral por U/CP que frequentavam o ambulat?rio de epilepsia do Servi?o de Neurologia do Hospital S?o Lucas da Pontif?cia Universidade Cat?lica do RS (PUCRS). Todos realizaram RNM, EEG, avalia??o motora e funcional.Resultados: Quinze pacientes (71%) apresentaram U, dois (9,8%) CP e quatro (19,2%) U + CP. Todos os EEGs estavam alterados, com predom?nio de lentifica??o multilobar (66,6%) e descargas multilobares (71%). A maioria dos pacientes (47,6%) apresentou combina??o de crise parcial simples (CPS) e complexa (CPC), evoluindo para secundariamente generalizada (CSG). Equil?brio diminu?do e dificuldades na realiza??o de atividades de vida di?ria foram comuns aos 21 pacientes.Conclus?o: altera??es motoras, advindas de les?es cerebrais, somadas a ocorr?ncia de crises epil?pticas impactam na capacidade funcional de pacientes com U/CP

Made available in DSpace on 2015-04-14T13:35:36Z (GMT). No. of bitstreams: 1 444693.pdf: 339452 bytes, checksum: ef9dfaf2d55534b68964afd3bb92e166 (MD5) Previous issue date: 2012-08-28 / The aim of this study was to check if there is a predictive relationship of measured serum levels of anti-Mullerian hormone (AMH), antral follicle count (AFC) and ovarian volume with the results of IVF. We conducted a prospective study between January 2010 and March 2012 with women aged 35 or more who underwent IVF. The levels of AMH, AFC and ovarian volume were correlated with response to ovarian hyperstimulation, with rates of fertilization, with embryo quality and pregnancy rates. We evaluated 40 patients with a median age of 39 years old. There was a significant direct correlation between the levels of AMH and the number of follicles larger than 14 mm (rS = 0.81 and P < 0.001). The same happened to the AFC (rS = 0.69 and P < 0.001). This correlation was not significant when evaluated the ovarian volume. AMH, AFC and ovarian volume did not show a statistically significant correlation with rates of fertilization, with embryo quality or with pregnancy rates. In predicting good or poor response, AMH and AFC showed a high positive predictive value (100% for the AMH and 87% for AFC, using a cutoff of 0.9 ng/ml and 7 follicles respectively, values established by ROC curve). We conclude from this study that AMH and AFC can be used as predictors of response to ovarian hyperstimulation in IVF, but they are not related to embryo quality, fertilization rates or pregnancy. / O objetivo deste estudo foi verificar se existe rela??o preditiva da medida do n?vel s?rico do horm?nio antim?lleriano (HAM), da contagem de fol?culos antrais (CFA) e do volume ovariano com os resultados de FIV. Realizou-se um estudo prospectivo no per?odo de janeiro de 2010 a mar?o de 2012 com mulheres de 35 anos ou mais que realizaram FIV. Os n?veis do HAM, CFA e volume ovariano foram correlacionados com resposta ? hiperestimula??o ovariana, com as taxas de fertiliza??o, com a qualidade dos embri?es e com os ?ndices de gesta??o. Foram avaliadas 40 pacientes com uma mediana de idade de 39 anos. Observou-se uma correla??o direta significativa entre os n?veis do HAM e o n?mero de fol?culos maiores de 14 mm (rS = 0,81 e P < 0,001), ocorrendo o mesmo com a CFA (rS = 0,69 e P < 0,001). Tal correla??o n?o foi significativa quando avaliado o volume ovariano. HAM, CFA e volume ovariano n?o apresentaram uma correla??o estatisticamente significativa com as taxas de fertiliza??o, com a qualidade embrion?ria, nem com os ?ndices gesta??o. Na predi??o de boa ou m? resposta, HAM e CFA apresentaram um alto valor preditivo positivo (100% para o HAM e 87% para a CFA, usando um ponto de corte de 0,9 ng/ml e 7 fol?culos respectivamente, valores estabelecidos pela curva ROC). Conclu?mos, com o estudo, que HAM e CFA podem ser utilizados como preditores da resposta ? hiperestimula??o ovariana em FIV; por?m, n?o est?o relacionados ? qualidade embrion?ria, taxas de fertiliza??o ou gesta??o.

Made available in DSpace on 2015-04-14T13:35:37Z (GMT). No. of bitstreams: 1 444782.pdf: 1327290 bytes, checksum: 51c0bcf62b76809d6ed98fd7aca7d6b9 (MD5) Previous issue date: 2011-03-15 / The Wilms Tumors (WT) is the most frequent renal tumors of children, and although curable, fatal outcomes may occur. A number a genetic alterations have been suggested as associated factors but still, the exact pathogenesis of WT remains to be fully characterized. Tissue factor (TF) is a glycoprotein which happens to be a key receptor for factor VII/VIIa and is the primary initiator of blood coagulation. Also important, TF has been associated with processes that lead to angiogenesis. It is widely expressed among cells and tissues and recent evidences pointed out an important role for TF in cancer progression and metastasis. Recent evidences suggested that TF may have a role in WT since its immunodetection was associated with poor prognosis. In the present investigation the differential expression of TF was assessed in WT using real-time PCR of RNA retrieved from paraffin sections using microdissection. Different histological components of WT - (blastema, epithelial and stromal) were analysed and the results revealed that TF in blastema and epithelial components was upregulated (14.38 and 16.02-fold respectively, P<0.001). Stroma and control non neoplasic tissues expressed similar levels of expression (P>0.05). TF expression in metastatic lesions from WT was also singificantly upregulated compared to non metastatic lesions. Microvessel density was positively correlated with TF expression (r=0.721). As described for other tumors, TF seems to play a role in malignancy or WT. Further investigations are warranted to better understand the pathways by which TF exerts its effects on tumor progression. Noteworthy, pharmacological strategies that aim at controlling angiogenesis through regulation of TF may be very promising / Esta pesqusisa teve como objetivo demonstrar a express?o diferencial do fator tecidual (FT) em tumor de Wilms (TW), atrav?s de um estudo do tipo transversal. O TW ? a neoplasia renal maligna mais comum na inf?ncia. Os estudos sobre angiog?nese em neoplasias malignas pedi?tricas apresentam poss?veis vias de terapias antiangiog?nicas, com menor agressividade e melhor especificidade tumoral. E, entre os fatores angiog?nicos poss?veis, foi estudo o Fator Tecidual (FT), prote?na transmebrana com sua principal fun??o no processo de hemostasia, mas que demonstra ter importante papel nos processos patol?gicos de tumorig?nese, angiog?nese e microambiente tumoral favor?vel ? dissemina??o neopl?sica. Sua express?o vem sendo associada ?s met?stases e piora no progn?stico. Contuto, s? a partir da pesquisa de Maciel et al (1) que a associa??o do FT com TW foi observada, onde se encontrou, utilizando imunoistoqu?mica, a correla??o positiva entre a express?o do FT, recidiva tumoral e ?bito. Ent?o, a partir desses dados iniciais, a presente pesquisa analisou uma amostra com 27 esp?cimes fixadas em parafina de TW e 26 controles (?rea sem TW), para demonstrar a express?o diferencial do FT em TW, atrav?s da t?cnica de quantifica??o de ?cidos nucl?icos (RNAm) por Rea??o Cadeia de DNA Polimerase em Tempo Real (RT-PCR), avaliar a express?o do FT em diferentes componentes tumorais, com a densidade microvascular (DMV) do TW e a ocorr?ncia de met?stases. Foi observado aumento da express?o diferencial do FT no TW, sua maior varia??o do FT foi encontrada nos componentes blastematoso e epitelial, enquanto no componente estromal apresentou varia??o m?nima em rela??o ao tecido n?o tumoral, em les?es metast?ticas o FT se mostrou significativamente mais elevado, sugerindo um papel importante para essa prote?na no processo de dissemina??o dessas c?lulas malignas, o aumento da DMV apresentou associa??o positiva com a express?o do FT. Os resultados apresentados corroboram os achados de Maciel et al (1) de forma mais concisa e quantitativa, enfatizando a import?ncia do FT na biologia do TW

Made available in DSpace on 2015-04-14T13:35:37Z (GMT). No. of bitstreams: 1 445040.pdf: 2039522 bytes, checksum: 2f433c611b99e5b28cbd56ef7aed5bb1 (MD5) Previous issue date: 2010-09-30 / Rationale: Comorbidity between difficult-to-treat epilepsies and ADHD is high, but because of concerns with the use of stimulants in this population, there is no data on the possible impact of such treatment.Objective: We studied the effect of methylphenidate in the quality of life of children and adolescents with DSM-IV criteria for ADHD and difficult-to-treat epilepsies.Methods: Open label, non-controlled trial, with intention-to-treat analysis following 30 patients for 6 months. Subjects received methylphenidate following 3 months of baseline, during which antiepileptic drugs (AEDs) were adjusted and epilepsy, ADHD and quality of life variables were assessed. Multivariate regression analysis identified the main variables correlated with outcome.Results: Only one patient withdrew because of seizure worsening. Following methylphenidate introduction, reaching doses of 0.40 - 0.50 mg/kg/day, a marked improvement in quality of life scores and a significant reduction in seizure frequency and severity were observed. Female sex, reduction of core ADHD symptom burden and tolerability to adequate doses of methylphenidate correlated with quality of life scores.Conclusion: These preliminary data suggest that methylphenidate treatment is safe and effective to patients with ADHD and difficult-to-treat epilepsies and has a positive impact on quality of life scores / Fundamentos - A associa??o entre epilepsia e TDAH ? altamente prevalente comprometendo a Qualidade de Vida de crian?as e adolescentes com crises epil?pticas. Metilfenidato Ritalina(R) - ? o medicamento de uso consagrado para o Transtorno de D?ficit de Aten??o/Hiperatividade com 80% de efic?cia em crian?as com TDAH com ou sem epilepsia. Questiona-se a possibilidade do MFD diminuir o limiar convulsivo dos pacientes epil?pticos.Objetivos - Avaliar a influ?ncia do uso de Metilfenidato sobre a Qualidade de Vida e o perfil das crises epil?pticas em crian?as e adolescentes com epilepsias de dif?cil controle.Pacientes e M?todos - Foi realizado um ensaio cl?nico aberto, n?o randomizado, com 30 crian?as e adolescentes do Ambulat?rio de Neuro-Epilepsias Graves apresentando crises de dif?cil controle e TDAH. Foram avaliadas quanto ? Qualidade de Vida, sintomas de TDAH e perfil das crises antes e ap?s o uso de MFD. Houve um ajuste/troca de FAE somente no tempo -3 (baseline). Metilfenidato foi iniciado ap?s estes 3 meses (T 0) sem outras modifica??es nos FAE com avalia??es 1 m?s e 3 meses ap?s. Foram avaliados tamb?m eventos adversos ao uso do MFD.Resultados - Ocorreu melhora da QV em todos os momentos avaliados: T -3 (baseline) a T0, T0 a T+1 e T+1 a T+3. A melhora ocorrida entre T-3 e T0, momento em que foi realizado o ajuste de FAE, n?o foi estatisticamente significativa. Nos tempos subseq?entes, com o uso de MFD, as varia??es de QV ocorridas apresentaram signific?ncia estat?stica. Ocorreu melhora da qualidade de vida com signific?ncia estat?stica em indiv?duos do sexo feminino, os que apresentaram in?cio mais tardio da doen?a e naqueles em houve maior diminui??o dos escores de d?ficit de aten??o. Os pacientes com crises generalizadas apresentaram piores ?ndices de QV. N?o houve associa??o estatisticamente significativa entre a varia??o da QV com a freq??ncia e/ou gravidade das crises, idade, dura??o da doen?a, QI, ocorr?ncia de eventos adversos.Conclus?es - Houve melhora da QV de pacientes epil?pticos de dif?cil controle tratados com MFD sem que houvesse piora na freq??ncia ou gravidade das crises. Condizente com a literatura tamb?m n?o verificamos a presen?a de efeitos colaterais de gravidade significativa ao MFD. Estes dados preliminares sugerem a possibilidade da utiliza??o deste f?rmaco no tratamento de crian?as e adolescentes com crises epil?pticas de dif?cil controle com a conseq?ente melhora de QV destes pacientes.

Made available in DSpace on 2015-04-14T13:35:38Z (GMT). No. of bitstreams: 1 445402.pdf: 4168826 bytes, checksum: 12e5afbd895c8db20632ed4bc6ddacbf (MD5) Previous issue date: 2012-12-20 / Background: Erythropoietin (EPO) and granulocyte colony stimulating factor (GCSF) have generated interest as novel therapies after myocardial infarction (MI), but the effect of combination therapy has not been studied in the large animal model.Objetives: We investigated the impact of prolonged combination therapy with EPO and GCSF on cardiac function, infarct size, and vascular density after MI in a porcine model.Methods: MI was induced in pigs by a 90 min balloon occlusion of the left anterior descending coronary artery. 16 animals were treated with EPO+GCSF, or saline (control group). Cardiac function was assessed by echocardiography and pressure-volume measurements at baseline, 1 and 6 weeks post-MI. Histopathology was performed 6 weeks post-MI.Results: At week 6, EPO+GCSF therapy stabilized left ventricular ejection fraction, (41?1% vs. 33?1%, p<0.01) and improved diastolic function compared to the control group. Histopathology revealed increased areas of viable myocardium and vascular density in the EPO+GCSF therapy, compared to the control. Despite these encouraging results, in a historical analysis comparing combination therapy with monotherapy with EPO or GCSF, there were no significant additive benefits in the LVEF and volumes overtime using the combination therapy.Conclusion: Our findings indicate that EPO+GCSF combination therapy promotes stabilization of cardiac function after acute MI. However, combination therapy does not seem to be superior to monotherapy with either EPO or GCSF / Introdu??o: Recentemente, a eritropoetina (EPO) e o fator estimulante de col?nia de granul?citos (GCSF) surgiram como potenciais terapias no tratamento do infarto agudo do mioc?rdio (IAM). Contudo, os efeitos da terapia combinada ainda est?o por ser investigados.Objetivo: Investigar a efic?cia e seguran?a da terapia combinada com EPO e GCSF p?s-IAM em um modelo porcino.M?todos: IAM foi induzido em porcos dom?sticos atrav?s da oclus?o por 90 minutos da coron?ria descendente anterior esquerda. Dezesseis animais foram tratados com an?logo de longa a??o da EPO a GCSF ou solu??o salina (grupo controle). Fun??o card?aca foi avaliada via ecocardiografia e medidas de press?o-volume no inicio do estudo, uma e seis semanas ap?s o IM. Histologia foi realizada seis semanas ap?s o IAM.Resultados: Seis semanas ap?s o IAM, a terapia combinada com EPO e GCSF demonstrou estabilizar a fra??o de eje??o ventricular esquerda (41?1% vs. 33?1%, p<0.01) e melhorar a fun??o diast?lica quando comparada com o grupo controle. Avalia??o histopatol?gica revelou aumento de ?reas de mioc?rdio vi?vel e de densidade vascular no grupo tratado com EPO e GCSF quando comparada com o grupo controle. Apesar dos resultados encorajadores, em uma avalia??o hist?rica comparando a terapia combinada com a monoterapia com EPO ou GCSF, a terapia combinada n?o demonstrou ter beneficio adicional na preserva??o da fra??o de eje??o ou volumes ventriculares ao longo do per?odo em estudo.Conclus?o: Os presentes achados sugerem que a terapia combinada com EPO e GCSF promove a estabiliza??o da fun??o card?aca ap?s o IAM. Contudo, a terapia combinada n?o aprece ser superior a monoterapia com EPO ou GCSF

Made available in DSpace on 2015-04-14T13:35:38Z (GMT). No. of bitstreams: 1 446128.pdf: 4314617 bytes, checksum: 28ae5dd4320a91899f6c6fcd8f7097b3 (MD5) Previous issue date: 2012-12-18 / Introduction : There have been national and international recommendations to estimate glomerular filtration rate as a predictor of kidney disease, in the general population, measuring plasma creatinine concentration. In pediatrics, however, there is a high incidence of factors that affect plasma creatinine concentration, such as growth rate and the equations most commonly used to estimate GFR are derivative from Bedside Schwartz formula. The serum cystatin C, an unglycosylated protein of low molecular weight, produced by all nucleated cells, has been proposed as a marker of glomerular filtration. In this context in Brazil, there have been doubts among professionals about using cystatin C in pediatrics, due to the lack of appropriate studies about it. Objective : We sought to investigate the transversal diagnostic accuracy, either related to cystatin C or plasma creatinine or both in comparison with inulin, for estimating changes in GFR in a prospective cohort of children with kidney disease. Patients and Methods : Firstly, we have chosen as methodological strategy for the estimation of GFR the measurement by inulin clearance, in pediatrics and in a young adult population, followed by a respective publication. Secondly, we have used repeated and simultaneous measurements of renal clearance by inulin in pediatric patients. The analysis has been performed by linear mixed model due to the number of repeated measurements from the same patient. In order to assess the equivalence between methods, we applied Bland & Altman graphics, as well as concordance correlation tests. In a second phase, we had cystatin C and serum creatinine measured in pediatric renal patients, including those patients who had undergone a transplant. Consequently, an article was submitted to publication and another one was submitted to analysis. Results : This thesis has generated four presentations at international scientific congresses, 4 articles and 1 book chapter in French (attached). Conclusions : The adequate measurement of GFR is of fundamental importance in clinical practice in all phases of one's life. The GFR progressively declines with time, in most renal diseases, which results in complications such as hypertension, anemia, malnutrition, bone disease, neuropathies. / Introdu??o : As recomenda??es internacionais e nacionais recomendam a aferi??o da taxa de filtra??o glomerular como preditor de doen?a renal na popula??o geral, com uso de creatinina plasm?tica. Entretanto, na pediatria existe uma alta preval?ncia de fatores que interferem na creatinina plasm?tica, dentre os quais a taxa de crescimento. As equa??es mais empregadas s?o derivadas da f?rmula de Schwartz abreviada (bedside). A cistatina C s?rica, uma prote?na n?o glicosilada de baixo peso molecular que ? produzida por todas as c?lulas nucleadas, tem sido apontada como um marcador de filtra??o glomerular. Nesse contexto, h? d?vidas em rela??o ? cistatina C na pediatria, devido ? escassez de estudos com delineamento adequado no Brasil. Objetivo : Avaliar transversalmente a acur?cia diagn?stica da cistatina C, creatinina plasm?tica, ou ambas em estimar mudan?as na TFG comparados ? inulina numa coorte prospectiva de crian?as com doen?a renal. Pacientes e M?todos : Em uma fase inicial, adquirimos a estrat?gia metodol?gica para a realiza??o da TFG por depura??o plasm?tica de inulina, em pediatria e na popula??o de adultos jovens, com respectiva publica??o. Ap?s, utilizou-se de medidas simult?neas e repetidas de depura??o renal de inulina em pacientes pedi?tricos. A an?lise foi realizada por modelo linear misto, devido ao n?mero repetido de medidas no mesmo paciente. Para avaliar a concord?ncia entre os m?todos foram utilizados gr?ficos de Bland Altman e teste de correla??o de concord?ncia. Em uma segunda fase, foram realizadas medidas de cistatina C e de creatinina plasm?tica em pacientes renais pedi?tricos, inclusive transplantados, com subsequente publica??o de um artigo e submiss?o de outro para an?lise. Resultados : Essa tese gerou 4 apresenta??es em congressos cient?ficos internacionais, 4 artigos e 1 cap?tulo de livro em franc?s (em anexo). Conclus?es : A aferi??o adequada da TFG ? de fundamental import?ncia na pr?tica cl?nica em todas as fases da vida do indiv?duo. A TFG declina progressivamente, com o tempo, na maioria das enfermidades renais, o que resulta em complica??es como hipertens?o arterial, anemia, desnutri??o, enfermidade ?ssea, neuropatias.

Made available in DSpace on 2015-04-14T13:35:38Z (GMT). No. of bitstreams: 1 446130.pdf: 1910036 bytes, checksum: 59d877dc63ef59118f780b6e08cf8f9f (MD5) Previous issue date: 2013-01-28 / Tuberculosis remains the most common cause of death due to an infectious agent. Among targets identified in Mycobaterium tuberculosis genome, enzymes of the shikimate pathway deserve special attention. Shikimate kinase is the fifth enzyme of the shikimate pathway, which has been identified in fungi, apicomplexans, plants and prokaryotes. This metabolic route is composed of seven steps, which converts erythrose-4-phosphate and phosphoenol pyruvate to chorismic acid and is responsible for the biosynthesis of aromatic amino acids. Shikimate kinase has been shown to be essential to the survival of Mycobacterium tuberculosis, and since it is absent in human, this enzyme is considered to be a target for chemotherapeutic for development of antitubercular drugs. The aim here is to identify possible inhibitors, focusing on simulations of molecular docking in the ATP-binding site of the enzyme. The program used in the simulations was the Molegro Virtual Docker and protein-ligand interactions were tested in 12 crystallographic structures and then, it was choosen a protocol which generated docking RMSD values below 2 ?. Application of this docking protocol to a decoy dataset generated a enrichment factor of 24.57, which is considered adequate for molecular docking simulations focused on kinases. The present docking protocol was then applied to a small-molecule database with over 80,000 entries. Analysis of the results identified 5 potencial shikimate kinase inhibitors. Examination of the intermolecular interaction between enzyme and the ligands identified the main structural features responsible for ligand-binding affinity. This is the first molecular docking study focused on the ATP-binding pocket of shikimate kinase. / A Tuberculose continua sendo a causa mais comum de morte em decorr?ncia de um agente infeccioso. Entre os alvos identificados no genoma do Mycobaterium tuberculosis, enzimas da via do chiquimato merecem aten??o especial. A chiquimato quinase ? a quinta enzima da via do chiquimato, e tem sido identificada em fungos, organismos do filo apicomplexa, plantas e procariontes. Esta via metab?lica ? composta por sete passos, que catalisam sequencialmente a convers?o de eritrose-4-fosfato e fosfoenolpiruvato em corismato; e ? respons?vel pela bioss?ntese de amino?cidos arom?ticos. Chiquimato quinase parece ser essencial para a sobreviv?ncia do Mycobacterium tuberculosis, uma vez que ? ausente no homem, esta enzima ? considerada como um alvo para o desenvolvimento de quimioter?picos e medicamentos contra a tuberculose. O objetivo ? identificar poss?veis inibidores, focando as simula??es de docking molecular no s?tio de liga??o do ATP da enzima. O programa usado nas simula??es foi o Molegro Virtual Docker e a intera??o prote?na-ligante foi testada em 12 estruturas cristalogr?ficas e logo ap?s, escolhido um protocolo de docking a partir de valores de RMSD abaixo de 2?. O m?todo foi validado usando o melhor protocolo de re-docking no Virtual Screening atrav?s do Fator de Enriquecimento que obteve resultado de 24,57%, que ? considerado adequado para as simula??es de docking molecular focados em quinases. O presente protocolo de docking foi aplicado em um banco de dados com mais de 80.000 mol?culas. A an?lise dos resultados identificaram 5 potenciais inibidores da chiquimato quinase. Na an?lise das intera??es intermoleculares entre a enzima e os ligantes foram identificadas caracter?sticas estruturais respons?veis pela afinidade da liga??o pelo ligante. Este ? o primeiro estudo de docking molecular focado no bols?o de liga??o do ATP da chiquimato quinase.

Made available in DSpace on 2015-04-14T13:35:39Z (GMT). No. of bitstreams: 1 446141.pdf: 2924471 bytes, checksum: 591d364936b0b745c1bf308039e89cb8 (MD5) Previous issue date: 2013-01-22 / Aim: The aim of this study was to evaluate the progress of cognitive functions (memory; focused attention; executive, visual and spatial functions; language and processing speed), emotional aspects (depression; anxiety), fatigue, and motor ability of lower and upper limbs in patients with multiple sclerosis, and their association with time and severity of disease.Methods: A cohort study with a comparison group. The sample was composed of 54 patients with a diagnosed of multiple sclerosis followed for 1-4 years in an neuroimmunology outpatient clinic, as compared to a control group of 30 individuals. As from the second year of the study, 33 patients and a group of 32 control individuals were evaluated using the Multiple Sclerosis Functional Composite (MSFC) measure. The cognitive performance was evaluated through psychological tests: Digits, Cubes, Vocabulary, Memory of Wechsler Scale-III, Stroop Test, Boston Naming Test, phonological and semantic Verbal Fluency, Clock Drawing, Mini Exam of Mental State (MEMS), Beck s Anxiety and Depression Inventories, Fatigue Scale (MFIS), and the MSFC.Results: There was a significant impairment of immediate and delayed verbal memory and phonological verbal fluency (FAS) in the group with multiple sclerosis, as well as lower performance than the controls in visual memory, sustained attention, working memory, processing speed and motor functions. The Expanded Disability Status Scale (EDSS) was found to be significantly correlated with tests of general cognitive evaluation (MEMS and estimated IQ), memory tests (immediate and delayed, visual and verbal), fluency tests (FAS and Animals), and executive function test (Stroop). No correlation was found of any of the neuropsychological tests with time of disease. Delayed memory and fluency were significantly correlated with depressive symptoms.Conclusion: A statistically significant correlation was found between the results of general cognition evaluations, of the findings from all tests of Memory of the Wechsler Scale, of the Verbal Fluency tests and of the Stroop test (attention and processing speed) and the scales that measure the severity of disease. Concerning the motor function, the patients with MS showed a major loss in motor ability of upper limbs. There is deterioration of the cognitive functioning associated with the progression of the disease in patients with Multiple Sclerosis. A combination of cognitive, emotional and physical aspects should be considered in evaluating patients with multiple sclerosis, without dissociating their functionality / Objetivo: este estudo teve como objetivo principal avaliar a evolu??o das fun??es cognitivas (mem?ria, aten??o concentrada, fun??es executivas e viso-espaciais, linguagem e velocidade de processamento), aspectos emocionais (depress?o e ansiedade), fadiga e habilidade motora dos membros superiores e inferiores nos pacientes portadores de esclerose m?ltipla e sua associa??o com tempo e gravidade da doen?a.Metodologia: Estudo de coorte com grupo de compara??o. A amostra foi constitu?da por 54 pacientes acompanhados de 1 a 4 anos no ambulat?rio de neuroimunologia com diagn?stico de esclerose m?ltipla, comparados a um grupo controle constitu?do por 30 indiv?duos. A partir do 2o ano do estudo, 33 pacientes e um grupo de 32 indiv?duos controles tamb?m foram avaliados com a bateria MSFC (&#8213;Multiple Sclerosis Functional Composite measure&#8214;). O desempenho cognitivo foi avaliado atrav?s dos testes neuropsicol?gicos: D?gitos, Cubos, Vocabul?rio, Mem?ria Wechsler Scale-III, Teste de Stroop, Teste de Nomea??o de Boston, Flu?ncia Verbal Fonol?gica e Sem?ntica, Desenho do Rel?gio, Mini Exame do Estado Mental, Invent?rios de Ansiedade e Depress?o de Beck, Escala de Fadiga-MFIS e a bateria MSFC.Resultados: Houve comprometimento significativo da mem?ria verbal imediata e tardia e fluencia verbal fonol?gica (FAS) no grupo com esclerose m?ltipla, bem como menor desempenho em compara??o com os controles na mem?ria visual, aten??o sustentada, mem?ria de trabalho, velocidade de processamento e fun??es motoras. Foi observada uma correla??o significativa do EDSS com os testes de avalia??o cognitiva global (MEEM e QI estimado), os testes de mem?ria (imediata e tardia, visual e verbal), os testes de flu?ncia (FAS e Animais) e com o teste de fun??es executivas (Stroop). N?o se observou correla??o de nenhum dos testes neuropsicol?gicos com o tempo de doen?a. As mem?rias tardias e a flu?ncia apresentaram uma correla??o significativa com os sintomas depressivos.Conclus?o: Foi encontrada uma correla??o estatisticamente significativa entre os resultados das avalia??es globais de cogni??o, dos achados de todos os testes de Mem?ria da Escala Wechsler, dos testes de Flu?ncia Verbal e do Teste Stroop (aten??o e velocidade de processamento) com as escalas que avaliam a gravidade da doen?a. Em rela??o ? fun??o motora, os pacientes com EM apresentaram uma perda mais importante na habilidade motora dos membros superiores. Ocorre deterioro do funcionamento cognitivo associado ? progress?o da doen?a em pacientes portadores de Esclerose M?ltipla. A combina??o de aspectos cognitivos, emocionais e f?sicos devem ser considerados na avalia??o destes pacientes, sem dissociar a sua funcionalidade

Made available in DSpace on 2015-04-14T13:35:39Z (GMT). No. of bitstreams: 1 447907.pdf: 1330104 bytes, checksum: aa19b9b9e07f197ddc88c5cc8fef09c7 (MD5) Previous issue date: 2013-03-22 / Background: Visceral obesity is associated with increased risk of cardiovascular disease when compared to peripheral obesity. Omentin, an adipokine produced in the visceral adipose tissue, is related to components of metabolic syndrome (MetS) and may be related to coronary artery disease (CAD) Objective: To evaluate the association between serum levels of omentin and CAD in patients with MetS. Design and Methods: Serum levels of omentin were measured in 75 patients with MetS in a case-control study nested in a cross-sectional study. Thirty-six patients had CAD, whereas 39 patients did not have this disorder. Results: Serum levels of omentin were lower in patients with CAD than in those without the disease, 293.03 ng/mL ( } 121.44) and 224.56 ng/mL ( } 97.75), respectively (P = 0009). Serum levels of omentin were divided into 4 percentile groups. The highest percentile of omentin (Q4) had a lower proportion of CAD when compared to the lowest percentile (Q1). Such proportion did not change after adjusting for age, sex, HDL, type 2 diabetes, and diastolic blood pressure (OR: 0.13, CI: 0.02-0.84, P = 0.032). / Introdu??o: Obesidade visceral esta associada a maior risco de doen?a cardiovascular, quando comparada a obesidade periferica. A omentina e uma adipocina produzida no tecido adiposo visceral e esta relacionada a fatores da Sindrome Metabolica (SM); e pode tambem estar relacionada a doenca arterial coronariana (DAC). Objetivo: Avaliar a associacao entre os niveis de omentina serica e doenca arterial coronariana em pacientes com Sindrome Metabolica. M?todos: A omentina serica foi avaliada em 75 pacientes com SM em estudo caso controle aninhado em um estudo transversal. Trinta e seis pacientes com doen?a arterial coronariana estabelecida e 39 pacientes sem doenca. Resultados: Os niveis sericos de omentina foram menores em pacientes com doenca arterial coronariana do que naqueles sem doenca, 293,03 ng/mL ( }121,44) e 224,56 ng/mL ( }97,75), respectivamente (P= 0.009). Niveis de omentina foram divididos em 4 grupos de percentis, e o maior percentil de omentina (Q4) teve menor proporcao de DAC do que o menor percentil (Q1), mesmo quando ajustados para idade e sexo, HDL, DM2 e PAD (OR:0,13, IC:0,02 a 0,84 ;P:0,032). Conclus?o: Em pacientes com SM, a omentina esta diminuida no grupo com DAC, e essa relacao parece estar inversamente proporcional aos niveis de omentina.

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&#61676;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&#61676;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.