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 (―Multiple Sclerosis Functional Composite measure‖). 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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 2015-04-14T13:35:40Z (GMT). No. of bitstreams: 1 447910.pdf: 2718272 bytes, checksum: 970052e8ca9abce5d0dd93f2976d56d7 (MD5) Previous issue date: 2013-03-15 / The emergence and spread of resistance mechanisms in Gram-negative bacilli have complicate the treatment of serious nosocomial infections. Due to the ineffectiveness of the automated detection of KPC producer isolates there is a need to develop better methodologies. One possibility is to evaluate the ertapenem resistance, which has greater sensitivity to detect the expression of KPC producing isolates. However, the specificity may be reduced due to the resistance attributed to other mechanisms, such as AmpC gene expression or ESBL production associated with the loss of porin. This study included 128 samples of Gram-negative bacilli of Klebsiella pneumoniae and Enterobacter spp. resistant to ertapenem. Disk diffusion and E-test? method were applied to determine the susceptibility to imipenem, meropenem and ertapenem. Isolates intermediate and resistant to ertapenem were evaluated and additional resistance mechanisms conferred by blaTEM, blaSHV, blaCTX-M, blaCTX-M-2 and blaKPC for Klebsiella pneumoniae and Enterobacter cloacae genes were investigated by PCR technique. The presence of outer membrane protein (OMP) was investigated by dot blot. The gene blaTEM was detected in 52.9% and 10.3%; blaSHV in 29.4% and 0.94%; blaCTX-M in 41.4% and 1.9%, and blaCTX-M-2 in 23.5% and 1.9% of K. pneumoniae and Enterobacter cloacae isolates, respectively. blaKPC gene was present in 12.6% of Enterobacter spp. isolates. The OmpC and OmpF were present in 3.8% of Enterobacter cloacae isolates. Resistance genes and outer membrane proteins carbapenemases producing strains indicates that several resistance mechanisms contribute to therapeutic failure and point to the need for better detection methods and surveillance strategies. / A emerg?ncia e dissemina??o dos mecanismos de resist?ncia em bacilos Gram-negativos t?m complicado o tratamento de s?rias infec??es nosocomiais. Devido ? inefic?cia dos sistemas automatizados na detec??o de isolados produtores de KPC (Klebsiella pneumoniae produtora de carbapenemase) h? a necessidade do desenvolvimento de melhores metodologias. Uma possibilidade ? avaliar os isolados quanto ? resist?ncia ao ertapenem, o qual tem maior sensibilidade para detectar a express?o dos isolados produtores de KPC. Contudo, a especificidade pode ser reduzida devido ? resist?ncia conferida por outros mecanismos, tais como a express?o do gene AmpC ou a produ??o de ESBL associado a perda de porina. Este estudo incluiu 128 amostras de bacilos Gram-negativos de Klebsiella pneumoniae e Enterobacter spp. resistentes ao ertapenem. O m?todo de disco difus?o e E-test? foram aplicados para determinar a suscetibilidade para imipenem, meropenem e ertapenem. Os isolados com suscetibilidade intermedi?ria e resistentes para ertapenem foram avaliados e posteriormente foram investigados os mecanismos de resist?ncia atrav?s da presen?a dos genes blaTEM, blaSHV, blaCTX-M, blaCTX-M-2 e blaKPC para Klebsiella pneumoniae e Enterobacter spp., por meio da t?cnica de PCR. A presen?a de prote?na da membrana externa (OMP) foi investigada por meio de dot blot. O gene blaTEM foi detectado em 52,9% e 10,3%; blaSHV em 29,4% e 0,94%; blaCTX-M em 41,4% e 1,9% e blaCTX-M-2 em 23,5% e 1,9% dos isolados de K. pneumoniae e Enterobacter spp., respectivamente. O gene blaKPC estava presente em 12,6% dos isolados de Enterobacter spp. As porinas OmpC e OmpF estavam presentes, concomitantemente, em 3,8% dos isolados de Enterobacter cloacae. A detec??o da presen?a dos genes de resist?ncia e as prote?nas da membrana externa nos isolados produtores de carbapenemases indica que eles podem estar associados aos diversos mecanismos de resist?ncia, contribuindo para a falha terap?utica e apontando para a necessidade de melhores m?todos de detec??o e estrat?gias de vigil?ncia.

Made available in DSpace on 2015-04-14T13:35:40Z (GMT). No. of bitstreams: 1 447905.pdf: 1868506 bytes, checksum: 2732c72b3521229898c09939d74b2b2d (MD5) Previous issue date: 2013-03-18 / BACKGROUND : Quality of life (QoL) is an important criterion in the follow-up of results of medical treatments. Works on the evaluation of QoL in the long term are scarce. The present study was a long-term cross-sectional observation of aspects of QoL of morbidly obese patients submitted to bariatric surgery. METHODS : The WHOQOL-100 instrument was administered to 295 grade II and III obese patients submitted to bariatric surgery grouped by up to 11 years of posoperative. RESULTS : The BMI of 47.5?8.2 kg/m? in the preoperative period was reduced to 31.6?6.5 kg/m? (P<0.001). The percentage of loss of excess weight was substantial and remained high (at least 63.6?26.6 %) in all groups. In the physical domain, the group operated 1 year ago showed a considerable increase in QoL score (10.5?2.4 to 14.6?2.9, P<0.001), while the group operated 11 years ago returned to preoperative scores (12.2?2.0 to 12.2?2.9, P=0.975), with results similar to those for the level of independence domain (11.6?2.8 to 16.3?3.0, P<0.001, and 13.0?2.5 to 14.5?2.8, P=0.087). In the psychological domain, there was a persistent gain. The other domains did not show considerable variations. CONCLUSION : The reduction in BMI and in percent loss of excess weight was maintained during 11 years. Bariatric surgery demonstrated a positive effect on the QoL of subjects mainly in the first 7 postoperative years in the physical and level of independence domains. In the psychological domain, the gains persisted up to 11 postoperative years. / INTRODU??O : A qualidade de vida (QV) ? um crit?rio importante no acompanhamento dos resultados de tratamentos m?dicos. Trabalhos de avalia??o de QV de longo prazo s?o escassos. A presente pesquisa realizou um estudo de observa??o transversal de longo prazo sobre aspectos da QV de pacientes obesos m?rbidos submetidos ? cirurgia bari?trica. M?TODOS : A escala de QV WHOQOL-100 foi aplicada em 295 pacientes obesos de graus II e III, submetidos ? cirurgia bari?trica, agrupados por at? 11 anos de p?s-operat?rio. RESULTADOS : O IMC de 47,5?8,2 kg/m? no pr?-operat?rio foi reduzido para 31,6?6,5 kg/m? (P<0,001). O percentual da perda do excesso de peso foi substancial e manteve-se elevado (pelo menos 63.6?26.6 %) em todos os grupos. No Dom?nio F?sico, o grupo operado h? 1 ano obteve importante acr?scimo no escore de QV (10,5?2,4 para 14,6?2,9, P<0,001), enquanto que o grupo operado h? 11 anos retornou ?s m?dias do pr?-operat?rio (12,2?2,0 para 12,2?2,9, P=0,975), com resultados semelhantes para o Dom?nio do N?vel de Independ?ncia (11,6?2,8 para 16,3?3,0, P<0,001 e 13,0?2,5 para 14,5?2,8, P=0,087). No Dom?nio Psicol?gico, houve ganho persistente na QV. Os demais Dom?nios do WHOQOL-100 n?o apresentaram varia??es estatisticamente significativas. CONCLUS?O : A redu??o do IMC e perda do excesso de peso foi mantida durante 11 anos. A cirurgia bari?trica demonstrou um efeito positivo sobre a QV dos pacientes, principalmente nos primeiros 7 anos de evolu??o no Dom?nios F?sico e N?vel de Independ?ncia. No Dom?nio Psicol?gico, os ganhos persistiram at? 11 anos de p?s-operat?rio.

Made available in DSpace on 2015-04-14T13:35:41Z (GMT). No. of bitstreams: 1 447898.pdf: 1408088 bytes, checksum: c93d094ed0aac173eb02d8b5c6481c61 (MD5) Previous issue date: 2013-03-15 / Renal cell carcinomas (RCCs) are among most the most lethal malignant neoplasms. Despite the evolution in the development of new drugs and imaging studies, mortality rates have increased around the world. Currently, to establish risks of mortality in RCC patients are classified according to scales and nomograms that can&#8215;t accurately predict clinical outcomes. The association between cancer and thromboembolic events is well known for a long time. A few years ago, researchers identified tissue factor as one of the proteins responsible for these phenomena and several studies have been conducted trying to correlate the expression of tissue factor with cancer. In 2009, a study conducted by our group described the important association between the immunohistochemical expression of tissue factor and mortality in patients with Wilms' tumours. The aim of the present study was to correlate the immunohistochemical expression tissue factor with prognostic factors and mortality in 58 patients surgically treated at Hospital S?o Lucas in the years 2004 to 2007, who had been followed for at least five years. / O c?ncer renal ? uma das neoplasias malignas mais letais. As taxas de mortalidade t?m crescido mundialmente a despeito da evolu??o do diagn?stico precoce e do surgimento de novos f?rmacos ativos na terapia da doen?a sist?mica. Atualmente, para se estabelecer riscos de morbimortalidade em c?ncer renal, os pacientes s?o classificados de acordo com escalas e nomogramas que ainda n?o conseguem predizer com acur?cia a evolu??o cl?nica dos mesmos. De longa data, j? sabemos da associa??o entre fen?menos tromboemb?licos e neoplasia. H? alguns anos, pesquisadores identificaram o fator tecidual como uma das prote?nas respons?veis por estes fen?menos e desde ent?o v?rios estudos t?m sido conduzidos tentando identificar em diferentes tipos tumorais a associa??o entre fator tecidual, tromboembolismo e neoplasia. Em 2009, nosso grupo analisou a correla??o da express?o imunoistoquimica do fator tecidual com sobrevida em pacientes com tumores de Wilms. Neste estudo, houve importante associa??o entre express?o elevada do fator tecidual e pior progn?stico. O objetivo do presente trabalho foi correlacionar a express?o imunoistoquimica deste mesmo fator tecidual com fatores progn?sticos e mortalidade em 58 pacientes portadores de tumores de c?lulas claras de rim submetidos a cirurgia no Hospital S?o Lucas da PUCRS nos anos de 2004 ? 2007 e que tiveram acompanhamento por pelo menos 5 anos.

Made available in DSpace on 2015-04-14T13:35:41Z (GMT). No. of bitstreams: 1 449049.pdf: 4601361 bytes, checksum: 2276ab000b49804c39de92d4bc7fd4ec (MD5) Previous issue date: 2013-03-05 / Introduction: Antiphospholipid syndrome (APS) is characterized by venous or arterial thromboses, fetal losses and thrombocytopenia, in the presence of antiphospholipid antibodies (aPL). CD4+CD25+Foxp3+ regulatory T (Treg) cell dysfunction has been documented in various autoimmune disorders, but not in antiphospholipid syndrome (APS) up to date. Methods: In this cross-sectional study, we aim to investigate CD4+CD25+Foxp3+ Treg cells and CD3 CD19+ B cells in patients with primary APS, APS secondary to systemic lupus erythematosus (SLE) and healthy controls. Cell subtypes were immunophenotyped using specific monoclonal antibodies (anti-CD3 CY5, anti-CD4 FITC, anti-CD25, anti-Foxp3, anti-CD19 PE) and flow cytometry. Results: Twenty and five patients with primary APS, 25 with APS secondary to SLE and 25 age- and sexmatched controls were studied. The percentage Treg cells and CD3 CD19+ B cells were found significantly lower in primary APS and APS secondary to SLE patients as compared to controls (all p < 0.05). Decreasing levels of circulating Treg cells correlated to higher scores of lupus activity (r=-0.75, p<0.0001). Number of circulating Treg cells did not significantly vary among users or nonusers of chloroquine, azathioprine and corticosteroids (p=0.90, p=0.76 and p=0.29, respectively). Conclusion: A dysfunction in CD4+CD25+Foxp3+ Treg cells may represent one of the mechanisms leading to autoimmunity in APS patients. The decreased number of CD3 CD19+ B cells of APS patients warrants further elucidation. / Introdu??o: A s?ndrome antifosfolip?dica (SAF) ? uma trombofilia autoimune caracterizada por trombose arterial e/ou venosa, morbidade gestacional e presen?a de anticorpos antifosfol?pides. As c?lulas T reguladoras (Treg) CD4+CD25+FoxP3+ desempenham importante papel no controle supressivo da resposta imune, sendo sua hipofun??o associada ? autoimunidade. Por sua vez, os linf?citos B, al?m de se comportarem como c?lulas autorreativas, podem deflagrar a produ??o de c?lulas Treg. Objetivo: Quantificar, originalmente, c?lulas Treg CD4+CD25+FoxP3+ e linf?citos B CD3-CD19+ em pacientes com SAF prim?ria e secund?ria comparativamente a controles sadios. Materiais e m?todos: O estudo, transversal controlado, incluiu a an?lise fenot?pica de c?lulas mononucleares de sangue perif?rico nos tr?s grupos de indiv?duos acima mencionados; as c?lulas foram marcadas com anticorpos monoclonais contra CD4 FITH, CD25 APC, FoxP3 PE, CD3 CY5 e CD19 PE e quantificadas por citometria de fluxo. Resultados: Vinte e cinco pacientes com SAF prim?ria, 25 com SAF secund?ria a l?pus eritematoso pareados por sexo e idade e 25 controles sadios participaram deste estudo. O valor encontrado, percentual e absoluto, de c?lulas CD4+CD25+FoxP3+ e de c?lulas B CD3-CD19+ nos pacientes com SAF prim?ria foi significativamente menor quando comparados a controles sadios (P<0,05). No grupo com SAF secund?ria, as c?lulas CD4+CD25+FoxP3+ e CD3-CD19+ tamb?m estiveram significativamente diminu?das em rela??o aos controles (P<0,05). O teste de Pearson revelou correla??o negativa entre n?mero de c?lulas CD4+CD25+FoxP3+ e SLEDAI em pacientes com SAF secund?ria (rS=-0,75, P<0,05); n?o houve associa??o entre n?mero de c?lulas Treg e uso de azatioprina (P=0,23), glicocortic?ides (P= 0,29) e cloroquina (P=0,12). Conclus?o: Pacientes com SAF prim?ria ou secund?ria tiveram definida deple??o de c?lulas Treg CD4+CD25+FoxP3+, o que pode ter contribu?do para os fen?menos autoimunes vistos na doen?a. A diminui??o do n?mero de c?lulas B CD3-CD19+ nestes pacientes deve ser elucidada em estudos futuros.

Made available in DSpace on 2015-04-14T13:35:42Z (GMT). No. of bitstreams: 1 449054.pdf: 8006379 bytes, checksum: c3053d3057f799b289c2e245d372e446 (MD5) Previous issue date: 2012-12-12 / Renal transplantation has been deemed the best treatment for patients with end stage renal disease. Mycophenolic acid is an immunosuppressant widely used in transplantation, acting as a potent, selective, non-competitive and reversible inhibitor of inosine monophosphate-dehydrogenase enzyme. Currently, two compounds are available: mycophenolate mofetil and mycophenolate sodium, both presenting with high rate of gastrointestinal complications. In clinical practice, patients are routinely prescribed with fixed doses, which can lead to drug exposure differences as great as 10 times. Therapeutic monitoring of Mycophenolic acid appears as a helping tool, useful for adjusting doses, individualizing therapy and promoting better understanding of drug interactions on the pharmacokinetics of Mycophenolic acid. Omeprazole is a widely prescribed drugs for transplanted patient, either as prophylaxis of gastric disorders or peptic ulcers therapy. However, literature data have hinted at a possible omeprazole interaction on Mycophenolic acid pharmacokinetics, by raising gastric pH and reducing its gastric absorption. The aim of the current study was to evaluate Mycophenolic acid levels in patients using mycophenolate mofetil or mycophenolate sodium with and without co-administration of omeprazole. The method for therapeutic drug monitoring of Mycophenolic acid seemed consistent with previously established validation parameters. There was no statistical difference in Mycophenolic acid levels of patients using either mycophenolate mofetil or mycophenolate sodium, with or without concomitant omeprazole; yet Mycophenolic acid plasma levels presented lower variance when omeprazole was concomitantly used, in both groups. / O transplante renal constitui-se no tratamento de escolha para pacientes com insufici?ncia renal cr?nica terminal. O ?cido micofen?lico ? um imunossupressor muito empregado no transplante, que age como um potente, seletivo, n?o competitivo e revers?vel inibidor da enzima inosina-monofosfato desidrogenase. Atualmente, dois compostos est?o dispon?veis: o micofenolato de mofetila e o micofenolato s?dico, ambos apresentando elevado ?ndice de complica??es gastrointestinais. Na pr?tica cl?nica, os pacientes s?o rotineiramente prescritos com doses fixas padr?o, o que pode levar a uma diferen?a de pelo menos 10 vezes na exposi??o ? droga. O monitoramento terap?utico do ?cido micofen?lico surge como uma ferramenta de apoio cl?nico, auxiliando no ajuste de doses, na individualiza??o da terapia, e promovendo maior entendimento quanto a intera??es medicamentosas na farmacocin?tica do ?cido micofen?lico. O omeprazol ? um dos f?rmacos muito prescritos para pacientes transplantados, seja na profilaxia de dist?rbios g?stricos, seja no tratamento de ?lceras p?pticas. Entretanto, dados da literatura v?em apontando uma poss?vel intera??o do omeprazol na farmacocin?tica do ?cido micofen?lico, por elevar o pH g?strico e diminuir sua absor??o. Assim, o objetivo desse trabalho foi realizar a valida??o de m?todo para monitoramento terap?utico do ?cido micofen?lico e realizar uma an?lise dos efeitos da coadministra??o de omeprazol nos n?veis plasm?ticos do ?cido micofen?lico em grupos de pacientes em uso de micofenolato mofetila ou micofenolato s?dico. O m?todo laboratorial desenvolvido e validado para monitoramento terap?utico do ?cido micofen?lico apresentou-se condizente com os par?metros de valida??o descritos na literatura. A an?lise dos n?veis de ?cido micofen?lico, quando co-administrado ou n?o omeprazol em pacientes em uso de micofenolato mofetila ou micofenolato s?dico, n?o demonstrou diferen?a estat?stica, mas se observou que tanto o grupo micofenolato mofetila quanto o micofenolato s?dico, em co-administra??o com omeprazol, apresentavam menor vari?ncia dos n?veis plasm?ticos de ?cido micofen?lico.