Made available in DSpace on 2015-04-14T13:35:49Z (GMT). No. of bitstreams: 1 452036.pdf: 1676220 bytes, checksum: 099b6754a6aea6b267cc1b8e2ae71a36 (MD5) Previous issue date: 2013-07-24 / Molecular Imaging is a technique that allows visualization, characterization and quantification of biochemical processes in a molecular and cellular level, in humans and other live organisms. Among all the technics available, it s possible to highlight PET (Positron Emission Tomography), which needs the administration of a radiotracer in the organism to be studied. Radiotracers or radiopharmaceuticals are molecules that possess a radioactive element in their composition. Nowadays, the most used PET radiopharmaceutical is fluorodeoxyglucose (18F) or [18F]FDG. This molecule is a glucose analogue that accumulates inside the cell, allowing glucose metabolism visualization. However, considering the use of glucose by the brain as its main energy source, this radiopharmaceutical accumulates in high rates in the normal brain, making difficult to see pathological processes. In order to visualize more specific alterations in the brain, many others radiotracers can be used, for example flumazenil (18F). Flumazenil (FMZ) shows high affinity for the benzodiazepine site in the GABAA receptor, acting as competitive antagonist. It s already known that GABAA receptors play a key role in neuronal excitability control, and expression deficiencies in these receptors are involved in many neurological and psychiatric disorders, such as epilepsy, anxiety, depression, schizophrenia, etc. Regarding epilepsy, it is believed that in the epileptogenic foci the GABAA receptor expression is reduced, the brain region where seizures start. For this reason, the aim of this work was to study flumazenil (18F) synthesis, as well as its purification and quality control analysis, in order to produce a molecule that can be used to localize the epileptogenic foci. The fluoride ion (18F-) was produced using PET Trace 16 MeV cyclotron from GE Healthcare, through the nuclear reaction 18O(p,n)18F, through the irradiation of enriched 18O water with accelerated protons. The flumazenil (18F) synthesis was performed in the automated synthesis module TRACERlab FX F-N from GE Healthcare, by nucleophilic aromatic substitution reaction. The established ideal reaction conditions were 145?C for 15 minutes, and 6,2mg precursor mass. The 18F- incorporation degree in the flumazenil molecule was 72?6% (n = 5), verified by reaction mixture analysis. In the last step flumazenil (18F) was purified through high performance liquid chromatography (HPLC) and reserve-phase tC18 cartridge, obtaining a product with a purity higher than 99%. The radionuclidic purity and identity were analyzed by gamma ray spectroscopy and half-life evaluation. Radiochemical purity was verified using thin layer chromatography (TLC) and HPLC. The chemical purity tested the presence of kryptofix 2.2.2, through a colorimetric test, and residual solvents (ethanol and acetonitrile) through gas chromatography (GC). The pH was verified using strips. All the results complied with the pharmacopeia using [18F]FDG as reference. Synthesis time was 80 minutes including purification steps and the overall yield was 9.3% (decay corrected). The radiopharmaceutical stability was analyzed for 8 hours, and no impurities were detected in this period. The method developed showed to be viable to produce flumazenil (18F), which can be used in pre-clinical and clinical studies in the future. The knowledge acquired with this work will allow the improvement of this technology in the country, and the research of new radiotracers for PET/CT imaging. / A Imagem Molecular ? uma t?cnica que permite a visualiza??o, caracteriza??o e quantifica??o de processos bioqu?micos a n?vel molecular e celular, em humanos e outros organismos vivos. Dentre as tecnologias dispon?veis, destaca-se o PET (Positron Emission Tomography - Tomografia por Emiss?o de P?sitrons) que necessita da administra??o do radiotra?ador ao organismo a ser estudado. Radiotra?adores ou radiof?rmacos s?o mol?culas que possuem um elemento radioativo em sua composi??o. Atualmente, o radiof?rmaco mais utilizado em PET ? o fludesoxiglicose (18F) ou [18F]FDG. Esta mol?cula ? um an?logo da glicose, que se acumula no interior da c?lula, permitindo a visualiza??o do metabolismo da glicose. Entretanto, considerando que o c?rebro utiliza basicamente a glicose como fonte de energia, este radiof?rmaco se acumula em altas taxas no c?rebro normal, dificultando a visualiza??o de processos patol?gicos. A fim de visualizar altera??es patol?gicas mais espec?ficas no c?rebro, v?rios outros radiotra?adores podem ser utilizados, como por exemplo o flumazenil (18F). O flumazenil (FMZ) apresenta alta afinidade pelo local de liga??o de benzodiazep?nicos do receptor GABAA, atuando como antagonista competitivo. Sabe-se que os receptores GABAA possuem um papel chave no controle da excitabilidade neuronal e que defici?ncias na express?o destes receptores est?o envolvidas em um grande n?mero de patologias neurol?gicas e psiqui?tricas, como epilepsia, ansiedade, depress?o, esquizofrenia e etc. Com rela??o a epilepsia, acredita-se que exista uma diminui??o da express?o dos receptores GABAA no foco epileptog?nico, regi?o do c?rebro geradora das crises epil?pticas. Desta forma, o objetivo deste trabalho foi estudar a s?ntese do flumazenil (18F), bem como sua purifica??o e as an?lises de controle de qualidade, visando produzir uma mol?cula que auxilie na localiza??o do foco epileptog?nico. O ?on fluoreto (18F-) foi produzido no c?clotron PET Trace 16 MeV da GE Healthcare, atrav?s da rea??o nuclear 18O(p,n)18F, decorrente da irradia??o da ?gua enriquecida com 18O pelos pr?tons acelerados. A s?ntese do flumazenil (18F) foi realizada no m?dulo automatizado TRACERlab FX F-N da GE Helthcare, atrav?s de uma rea??o de substitui??o nucleof?lica arom?tica. As condi??es ideais de rea??o foram estabelecidas em 145?C durante 15 minutos, sendo que a massa do precursor foi de 6,2mg. A taxa de incorpora??o do 18F- na mol?cula do flumazenil foi de 72?6% (n = 5), verificado atrav?s da an?lise da mistura de rea??o. Na fase final o flumazenil (18F) foi purificado atrav?s de cromatografia l?quida de alta efici?ncia (CLAE) e cartucho de fase-reversa tC18, obtendo-se um produto com grau de pureza superior a 99%. A pureza e identidade radionucl?dica foram avaliadas atrav?s de espectroscopia de raios gama e do tempo de meia-vida. A pureza radioqu?mica foi verificada por cromatografia em camada delgada (CCD) e CLAE. Na an?lise da pureza qu?mica verificou-se a presen?a de kryptofix 2.2.2, atrav?s de teste colorim?trico, e solventes residuais (etanol e acetonitrila) por cromatografia gasosa (CG). O pH foi analisado utilizando fitas. Os resultados obtidos foram dentro dos limites estabelecidos pela farmacop?ia levando em considera??o o [18F]FDG. O tempo total de s?ntese foi de 80 minutos e o rendimento total foi de 9,3% (corrigido pelo decaimento). A estabilidade do radiof?rmaco foi analisada durante 8 horas, sendo que nenhuma impureza foi detectada neste per?odo. O m?todo desenvolvido mostrou ser vi?vel para produ??o do flumazenil (18F), podendo este ser futuramente utilizado em estudos pr?-cl?nicos e cl?nicos. Os conhecimentos adquiridos com este trabalho permitir?o o avan?o desta tecnologia no pa?s, e a pesquisa de novos radiotra?adores para a realiza??o de exames PET/CT.

Made available in DSpace on 2015-04-14T13:35:50Z (GMT). No. of bitstreams: 1 452619.pdf: 1154303 bytes, checksum: 1c5fd674a322085ab06b90525da4401a (MD5) Previous issue date: 2013-07-22 / Introduction: Coxa brevis is a deformity of the proximal femur caused by a decrease or absence of growth of the physis of the proximal femur, usually caused by avascular necrosis present condition in conditions such as developmental dysplasia of the hip, proximal femoral epiphysiolysis, septic arthritis or disease Legg-Calv?-Perthes disease. Several surgeries have been proposed to lower the greater trochanter and femoral neck lengthening reestablishing the anatomy. Objective: To compare the mechanical tests by polyurethane in bone models the compressive strength of two different assemblies of plates for fixing osteotomy "L" of the proximal femur. Material and Methods: We used anatomical models of the proximal femur polyurethane which underwent an osteotomy longitudinal and divided into two groups with one group fixed with 4.5 DCP plate 10 holes with four screws proximal and three distal screws and fixed with a group 4.5 DCP plate 6 holes with two proximal and two distal screws. The anatomical models were tested for flexo in mechanical universal testing machine and was evaluated relative stiffness and linear movement. Results: By comparing the two groups in flexo tests, the average value of the relative stiffness in group 1 set with the long plate was 386.17 x10-3 N / m. In the group with the smaller plate fixed average value of the relative stiffness was 261,89 x10-3 N / m. The average linear displacement observed for an applied force of 1000 N in group 1 was 2.53 x10-3. In group 2, the mean value of linear displacement was 3.49 x 10-3m. Conclusion: Based on the parameters measured in the tests flexo, stability obtained by fixing the first group with a plate of ten holes was significantly higher than that obtained by fixing the second group with six holes of the plate. / Introdu??o: Coxa brevis ? uma deformidade do f?mur proximal causada pela diminui??o ou aus?ncia de crescimento da fise da extremidade proximal do f?mur, geralmente causada por necrose avascular condi??o presente nas patologias como displasia do desenvolvimento do quadril, epifisi?lise femoral proximal, artrite s?ptica ou doen?a de Legg-Calv?-Perthes. Diversas cirurgias tem sido propostas para rebaixar o grande troc?nter ou alongar o colo femoral reestabelecendo a anatomia. Objetivo: comparar atrav?s de testes mec?nicos em modelos ?sseos de poliuretano a resist?ncia ? compress?o entre duas montagens diferentes de placas para fixa??o osteotomia em L do f?mur proximal. Material e M?todos: Foram utilizados modelos anat?micos de f?mur proximal em poliuretano no qual foi realizado uma osteotomia longitudinal e divididos em dois grupos sendo um grupo fixado com placa 4,5 DCP 10 furos com quatro parafusos proximais e tr?s parafusos distais e um grupo fixado com placa 4,5 DCP 6 furos com dois parafusos proximais e dois distais. O modelos anat?micos foram submetidos a teste de flexocompress?o em m?quina universal de ensaios mec?nicos e foi avaliado a rigidez relativa e o deslocamento linear. Resultados: Ao comparar os dois grupos nos ensaios de flexocompress?o, o valor m?dio da rigidez relativa no grupo 1 fixado com a placa longa foi de 386,17 x10-3 N/m. No grupo fixado com a placa menor o valor m?dio da rigidez relativa foi de 261,89 x10-3 N/m. O valor m?dio do deslocamento linear, observado para uma for?a aplicada de 1000 N, no grupo 1 foi de 2,53 x10-3. No grupo 2 o valor m?dio do deslocamento linear foi de 3,49 x10-3m. Conclus?o: Com base nos par?metros analisados nos ensaios de flexocompress?o, a estabilidade obtida pela fixa??o do grupo 1 com placa de dez furos foi significativamente maior que a obtida pela fixa??o no grupo 2 com a placa de seis furos.

Made available in DSpace on 2015-04-14T13:35:51Z (GMT). No. of bitstreams: 1 452950.pdf: 1650025 bytes, checksum: d2d9176381fad308a3ded6adffbce4e4 (MD5) Previous issue date: 2013-07-30 / Background: Fluid overload (FO) is common in patients on PD and the combination with inadequate nutritional status causes increased mortality in peritoneal dialysis (PD) patient. Bioimpedance spectroscopy is a precise, sensitive and reliable tool for determining the fluid volume status and body composition of PD patients. The main aims of this study were: to compare body composition and volume variables, measured with the dialysis fluid inside the peritoneal cavity (CC) and after its drainage (EC), using the Body Composition Monitor (BCM); and to evaluate associations of the nutritional status and body composition of patients receiving PD, with their volume status. Methods: A cross-sectional study involving 37 stable adult patients (>18 years) on PD. A BCM report was used for the analysis of fluid status and body composition, and was conducted with both a CC and EC. Results: The study sample had the following characteristics: 62.5% female, 68.8% Caucasian, 75.0% on continuous ambulatory peritoneal dialysis (CAPD) and 25.0% on peritoneal dialysis automatized (APD). Evaluation of 32 patients showed no statistical difference between CC and EC in regard to overhydration (OH), total body water, extracellular water, intracellular water and their corrections for height and weight, lean tissue mass, fat tissue mass and their indices, adipose tissue mass, and body cell mass. Pearson's correlation coefficient of OH between CC and EC was r=0.989 (P<0.001). Bland-Altmann plot for OH full and OH empty had a line of bias of -9 mL and 95% limits of agreement from -603 to 585 ml. In another analysis with 37 patients serum albumin was higher in euvolemic (EV) patients (P=0.013), and the Subjective Global Assessment and Malnutrition Inflamation Score were higher in OH patients (P=0.002 and P=0.004, respectively). All hypertensive patients were diagnosed as OH. Several correlations were disclosed between nutritional markers and body composition markers and volemia. Conclusion: The presence of intraperitoneal fluid does not interferes with the evaluation of hydration status using BCM, or in the analysis of corporal composition - lean tissue mass, fat tissue mass, adipose tissue mass and their indices, suggesting that the BCM methodology can be applied in both conditions, with or without drainage of the dialysate solution. Besides the volume status of PD patients has a strong association with nutritional assessment variables. Consequently, a detailed evaluation of volume status should be part of a complete nutritional assessment, aiming an appropriate nutritional state. / Introdu??o: A sobrecarga h?drica (SH) ? um achado comum em pacientes em di?lise peritoneal (DP) e a combina??o com a inadequa??o do estado nutricional aumenta a mortalidade desta popula??o. A bioimped?ncia espectrosc?pica ? uma ferramenta precisa, sens?vel e confi?vel para determinar o estado vol?mico e a composi??o corporal de pacientes em DP. O principal objetivo deste estudo foi: comparar a composi??o corporal e as vari?veis de volume, medidas com o l?quido de di?lise presente na cavidade peritoneal (CC) e ap?s este ser drenado (EC), atrav?s do Body Composition Monitor (BCM); e avaliar as rela??es do estado nutricional e composi??o corporal de pacientes em DP de acordo com a volemia. M?todos: Estudo transversal, envolvendo 37 pacientes adultos (>18anos de idade) est?veis em DP. Os dados gerados pelo BCM foram utilizados para an?lise da volemia e da composi??o corporal, realizados em dois momentos, CC e EC. Resultados: As caracter?sticas da amostra em estudo foram: 62,5% mulheres, 68,8% caucasianos, 75,0% em CAPD e 25,0% em APD. A avalia??o de 32 pacientes mostrou que n?o h? diferen?a estat?stica entre CC e EC em rela??o ? hiper-hidrata??o (OH), ?gua corporal total, intra e extracelular e suas corre??es por altura e peso, massa magra, massa gorda e seus ?ndices, massa de tecido adiposo e massa celular corporal. A correla??o de Pearson entre OH-CC e OH-EC apresentou valor de r=0,989 (P<0,001). Bland-Altmann plot para OH-CC e OH-EC mostrou linha de vi?s de -9mL e 95% de limites de concord?ncia (-603 a 585 mL). Em outra an?lise com 37 pacientes a albumina s?rica foi maior em pacientes euvol?micos (EV) (P=0,013), e a Avalia??o Subjetiva Global e o Escore de Desnutri??o-Inflama??o foram maiores em pacientes hiperhidratados (P=0,002 e P=0,004, respectivamente). Todos hipertensos foram diagnosticados como hiperhidratados. Diversas correla??es foram encontradas entre marcadores de estado nutricional e composi??o corporal com volemia. Conclus?o: A presen?a de l?quido intraperitoneal n?o interfere na avalia??o do estado de hidrata??o atrav?s do uso do BCM, assim como a an?lise da composi??o corporal massa magra, massa gorda, massa de tecido adiposo e seus ?ndices sugerindo que a metodologia do BCM pode ser aplicada em ambas as condi??es, com e sem o l?quido presente na cavidade peritoneal. Al?m disso, as vari?veis de volemia estudadas apresentam forte associa??o com vari?veis de estado nutricional. Com isso, observa-se que uma avalia??o detalhada do estado de hidrata??o deve fazer parte da avalia??o nutricional criteriosa, visando determinar corretamente o estado nutricional destes pacientes.

Made available in DSpace on 2015-04-14T13:35:52Z (GMT). No. of bitstreams: 1 455924.pdf: 866376 bytes, checksum: 11973f76ada2aeeeb6a5dcd6c7c51f89 (MD5) Previous issue date: 2014-01-02 / Paraquat (PQ) is an agrochemical agent commonly used worldwide, which is allied to potential risks of intoxication. This herbicide induces the formation of reactive oxygen species (ROS) that ends up compromising various organs, particularly the lungs (by the polyamine uptake system), and the brain (by dopaminergic neuronal cell loss). This study evaluated the deleterious effects of paraquat on the central nervous system (CNS) (changes in physiologic parameters, nociceptive responses, locomotor activity and motor coordination, and expression profile of some inflammatory markers), or peripherally (inflammatory cells in the blood and lungs), with special attempts to assess the putative protective effects of the selective CXCR2 receptor antagonist SB225002 on these parameters. PQ-toxicity was induced in male Wistar rats, in a total dose of 50 mg/kg, given by the intraperitoneal (i.p.) route (10 mg/kg each three days). Control animals received saline solution (10 ml/kg) at the same schedule of administration. Separate groups of animals were treated with the selective CXCR2 antagonist SB225002 (1 or 3 mg/kg, i.p.), administered 30 min before each paraquat injection. The major changes found in paraquat-treated animals were: decreased body weight and hypothermia, nociception behavior, impairment of locomotor and gait capabilities, enhanced TNF-&#945; and IL-1&#946; expression in the striatum, and cell migration to the lungs and blood. Some of these parameters were reversed when the antagonist SB225002 was administered, including recovery of physiological parameters, decreased nociception, improvement of gait abnormalities, modulation of striatal TNF-&#945; and IL-1&#946; expression, and decrease of neutrophil migration to the lungs and blood. Taken together, our results demonstrate that damage to the central and peripheral systems elicited by paraquat can be prevented by the pharmacological inhibition of CXCR2 chemokine receptors. The experimental evidence presented herein extends the comprehension on the toxicodynamic aspects of paraquat, and opens new avenues to treat intoxication induced by this herbicide. / O paraquat (PQ) ? um composto qu?mico bastante utilizado no mundo, o qual ? aliado a potenciais riscos de intoxica??o. Este herbicida induz a forma??o de esp?cies reativas de oxig?nio (ROS) que podem comprometer v?rios ?rg?os, especialmente os pulm?es (atrav?s da recapta??o de poliaminas), e o c?rebro (pela perda de neur?nios dopamin?rgicos). Este trabalho avaliou os efeitos delet?rios do paraquat frente ao Sistema Nervoso Central (SNC) (como mudan?as nos par?metros fisiol?gicos, respostas nociceptivas, atividade locomotora e coordena??o motora, e o perfil de express?o de alguns marcadores moleculares de inflama??o), e perif?rico (como c?lulas inflamat?rias no sangue e pulm?es), com o objetivo de avaliar o poss?vel papel protetor do antagonista de receptores de quimiocinas CXCR2, o SB225002, nestes par?metros. A toxicidade ao paraquat foi induzida em ratos machos Wistar, em uma dose total de 50 mg/kg, administrada intraperitonealmente (i.p.) (10 mg/kg a cada tr?s dias). Animais do grupo controle receberam solu??o salina (10 ml/kg) no mesmo protocolo de administra??o. Diferentes grupos de animais foram tratados com o antagonista SB225002 (1 ou 3 mg/kg, i.p.), administrado 30 minutos antes de cada aplica??o do paraquat. As prinicpais mudan?as encontradas nos animais tratados com paraquat foram: diminui??o do peso corporal e hipotermia, aumento da resposta nociceptiva, diminui??o da capacidade de marcha e locomo??o, aumento da express?o de TNF-&#945; e IL-1&#946; no estriado, e a migra??o de c?lulas inflamat?rias no sangue e pulm?es. Alguns destes par?metros foram revertidos quando administrado o antagonista SB225002, como recupera??o dos par?metros fisiol?gicos, diminui??o da nocicep??o, melhora na atividade de marcha, modula??o da express?o estriatal de TNF-&#945; e IL-1&#946;, e diminui??o da migra??o neutrof?lica para o sangue e pulm?es. Em conjunto, nossos resultados demonstram que os danos causados pelo paraquat ao sistema central e perif?rico podem ser prevenidos atrav?s da inibi??o farmacol?gica dos receptores de quimiocinas CXCR2. A evid?ncia experimental aqui apresentada extende a compreens?o dos efeitos toxicodin?micos do paraquat, e proporciona novas possibilidades para tratar a intoxica??o causada por este herbicida.

Made available in DSpace on 2015-04-14T13:35:52Z (GMT). No. of bitstreams: 1 455930.pdf: 2412584 bytes, checksum: f510a7887fb6fa3e2f006d9db557d511 (MD5) Previous issue date: 2014-01-24 / Spinal voltage-gated calcium channels (VGCC) are pivotal regulators of painful and inflammatory alterations, representing attractive therapeutic targets. We examined the effects of epidural administration of the selective P/Q- and N-type VGCC blockers Tx3-3 and Ph&#945;1&#946;, respectively, isolated from the spider P. nigriventer, on symptomatic, inflammatory and functional changes allied to cyclophosphamide (CPA)-induced hemorrhagic cystitis (HC) in mice. The effects of P. nigriventer-derived toxins were compared to those displayed by MVIIC and MVIIA, extracted from the cone snail C. magus. HC was induced by a single intraperitoneal injection of CPA (300 mg/kg). The spinal blockage of P/Q-type VGCC by Tx3-3 and MVIIC, or N-type VGCC by Ph&#945;1&#946; attenuated nociceptive and inflammatory events associated with HC, including bladder oxidative stress and cytokine production. Moreover, CPA produced an evident increase of bladder TRPV1 and TRPA1 mRNA expression, which was virtually reversed by all the tested toxins. Noteworthy, Ph&#945;1&#946; strongly prevented bladder neutrophil migration, besides HC-related functional alterations. Finally, the spinal co-administration of the selective NK1 receptor antagonist CP-96345 heightened Ph&#945;1&#946; antinociceptive effects. Our results shed new lights on the role of spinal P/Q and N-type VGCC in bladder dysfunctions, pointing out Ph&#945;1&#946; as a promising alternative for treating complications associated to CPA-induced HC. / Os canais de c?lcio voltagem-dependentes (CCVDs), ao n?vel medular, s?o um dos principais reguladores das altera??es inflamat?rias e dolorosas, representando um interessante alvo terap?utico. Com isso, avaliamos os efeitos da administra??o intratecal dos bloqueadores seletivos dos CCVD do subtipo P/Q e N, Tx3-3 e Ph&#945;1&#946;, respectivamente, isolados do veneno da aranha P. nigriventer, nas mudan?as sintom?ticas, inflamat?rias e funcionais, relacionadas com a cistite hemorr?gica (CH), induzido pelo quimioter?pico ciclofosfamida (CPA) em camundongos. Os efeitos dos pept?deos provenientes da aranha P. nigriventer foram comparados com os exibidos pelas toxinas MVIIC e MVIIA, obtidas do caramujo C. magus. A CH foi induzida por uma ?nica administra??o intraperitoneal de CPA (300 mg/kg). O bloqueio medular dos CCVD do subtipo P/Q atrav?s da Tx3-3 e MVIIC ou, o bloqueio dos CCVD do subtipo N pela toxina Ph&#945;1&#946; atenuou as respostas nociceptivas e inflamat?rias associadas ? CH, incluindo estresse oxidativo e produ??o de citocinas na bexiga. Al?m disso, a CPA produziu um aumento evidente na express?o do RNAm de TRPV1 e TRPA1 na bexiga, o qual foi virtualmente revertido por todas as toxinas. Notavelmente, a isoforma Ph&#945;1&#946; reduziu a migra??o de neutr?filos para a bexiga, al?m de reverter as disfun??es da bexiga relacionadas ? CH. Finalmente, a co-administra??o medular do antagonista seletivo dos receptores NK1, CP-96345, com o pept?deo Ph&#945;1&#946;, intensificou o efeito antinociceptivo do mesmo. Nossos resultados trazem novas evid?ncias da fun??o dos CCVD do subtipo P/Q e N ao n?vel medular na disfun??o da bexiga, apontando a Ph&#945;1&#946; como uma poss?vel alternativa de tratamento para complica??es associadas ? CH, induzida por CPA.

Made available in DSpace on 2015-04-14T13:35:53Z (GMT). No. of bitstreams: 1 457548.pdf: 766828 bytes, checksum: 22a981e2f27dd96bd986b29478dc3ae1 (MD5) Previous issue date: 2013-03-25 / Metabolic Surgery for the treatment of type 2 Diabetes Mellitus (T2DM) in patients not morbidly obese (BMI <35 kg/m2) has been widely studied. Taking into account that approximately 12% of pancreas transplants are performed in T2DM patients, we tought to evaluate the impact of the metabolic surgery in the management of obese T2DM on the waiting lists for pancreas transplant. We performed a Roux-en-Y gastrointestinal bypass in 5 insulin-dependent T2DM patients, candidates for pancreas after kidney transplant, with BMI <35 kg/m2. Three patients became insulin independent by the end of the first year while the other two have reduced insulin requirements by 70%. Furthermore, all patients achieved improved control on lipids levels. We conclude the surgery is effective in controlling blood glucose and lipids metabolism in obese T2DM kidney transplant recipients. In this population, a pancreas transplant, along with its associated morbidity, may be avoided. / A cirurgia metab?lica para tratamento do Diabetes Mellitus tipo 2 (DM2) em pacientes sem obesidade m?rbida (IMC <35 kg/m2) vem sendo amplamente estudada. Levando em conta que aproximadamente 12% dos transplantes de p?ncreas s?o realizados em pacientes com DM2, pensamos em avaliar o impacto da cirurgia metab?lica no manejo de obesos, diab?ticos tipo 2, em lista de espera para transplante de p?ncreas. Realizamos o bypass gastrointestinal em Y de Roux em 5 pacientes diab?ticos tipo 2, insuino-dependentes, candidatos ao transplante de p?ncreas ap?s rim, com IMC<35 kg/m2. Tr?s pacientes tornaram-se insulino independentes ao final do primeiro ano, enquanto os outros dois reduziram sua necessidade insulinica em torno de 70%. Al?m disto, todos os pacientes obtiveram melhora no controle dos lip?dios. Conclu?mos que a cirurgia ? efetiva no controle da glicemia e no metabolismo dos lip?deos em pacientes obesos, transplantados renais, com DM2. Nesta popula??o de pacientes, o transplante de p?ncreas, com suas co-morbidades associadas, pode ser evitado.

Made available in DSpace on 2015-04-14T13:35:53Z (GMT). No. of bitstreams: 1 457561.pdf: 511212 bytes, checksum: a1a63d3229f283b583a6b5e9517ed0a7 (MD5) Previous issue date: 2014-03-31 / Objective: Omentin is an adipokine expressed in visceral adipose tissue that has been associated with positive effects on metabolism. The objective of this study was to assess whether changes occur in circulating omentin levels and cardiovascular risk factors after abdominal subcutaneous liposuction with or without abdominoplasty. Materials and methods: Serum omentin levels and cardiovascular risk factors (blood pressure, lipid profile, and waist circumference) were assessed in 21 women at baseline and 8 to 12 weeks after abdominal liposuction with or without abdominoplasty. Weight, blood glucose levels, insulin levels, and the homeostasis model assessment (HOMA) index were also evaluated. Results: At 12-week follow-up, circulating omentin levels had not changed significantly from baseline (P = 0.11; effect size - ES = 0.37). Waist circumference was significantly decreased (P < 0.001; ES = -1.38). Blood pressure, lipid profile, blood glucose levels, insulin levels, and HOMA index were statistically unchanged. Conclusion: Abdominal subcutaneous liposuction, whether alone or with abdominoplasty, was not associated with significant changes in circulating omentin levels or cardiovascular risk factors / Objetivo: Omentina ? uma adipocina expressada no tecido adiposo visceral e associada a efeitos positivos sobre o metabolismo. Nosso objetivo foi avaliar se ocorre altera??o nos n?veis circulantes de omentina e em fatores de risco cardiovascular ap?s lipoaspira??o subcut?nea abdominal associada ou n?o ? abdominoplastia. Materiais e m?todos: N?veis s?ricos de omentina e fatores de risco cardiovascular, tais como: press?o arterial, perfil lip?dico e circunfer?ncia abdominal, foram avaliados em 21 mulheres antes e 8 a 12 semanas ap?s lipoaspira??o abdominal associada ou n?o ? abdominoplastia; peso, glicemia, insulina e ?ndice HOMA tamb?m foram estudados. Resultados: N?veis circulantes de omentina n?o se alteraram significativamente 12 semanas ap?s (P = 0,11; tamanho de efeito - E/S = 0,37); circunfer?ncia abdominal alterou significativamente (P<0,001; E/S = -1,38), enquanto outros fatores de risco cardiovascular, como press?o arterial e perfil lip?dico, n?o alteraram significativamente; glicemia, insulina e ?ndice HOMA tamb?m n?o alteraram significativamente. Conclus?o: Lipoaspira??o subcut?nea abdominal isolada, ou associada ? abdominoplastia, n?o levou a altera??es significativas nos n?veis de omentina nem em fatores associados ao aumento de risco cardiovascular

Made available in DSpace on 2015-04-14T13:35:54Z (GMT). No. of bitstreams: 1 457569.pdf: 482302 bytes, checksum: 7d0e339871cad4e249f766e39fa5ae38 (MD5) Previous issue date: 2003-03-26 / Objective : The study attempted to estimate the prevalence of metabolic syndrome (MS) in seniors presenting at the Geriatrics Outpatient Service and analyze the association of metabolic syndrome with morbidity and mortality after a five-year follow-up. Method : A historic cohort study was carried out with patients attending the outpatient service from January through December 1998, at age 60 or older. In the first stage, patient charts were extensively reviewed, identifying patients with metabolic syndrome (MS), morbidity and lifestyle. At the second stage, the patients and/or their families were called for death reports in the period and its possible cause. A descriptive, comparative and multivariate analysis was conducted, and the survival curve was calculated as established by Cox and Kaplan-Meier. Results : Of a total of 383 old patients that attended the outpatient clinic in the period investigated, 283 (73.9%) were contacted. The comparison between the contacted sample and the missing one didn t show differences, suggesting the missing group wouldn t imply bias in the sample.The main results included the observation of: (1) 26.5% (75) MS prevalence; (2) 5.3% (15) mortality in the follow-up period among the seniors investigated, with only one MS patient dying in the period; (3) in the group affected, in addition to morbidities associated to the diagnosis (hypertension, diabetes, obesity, and dyslipidemia), the following disorders were significantly associated to MS: acute myocardial infarction and stable angina. Unlike other morbidities, osteoporosis was inversely associated to MS; (4) given the reduced number of individuals that died, no association between MS and mortality was observed in the study period. Conclusion : In spite of no association with mortality, most results related to MS are in agreement with literature and suggest that this disease is of great impact on geriatric practice. / Objetivo : o estudo realizado buscou estimar a preval?ncia de s?ndrome metab?lica em idosos que freq?entavam um Servi?o Ambulatorial de Geriatria e analisar a associa??o de s?ndrome metab?lica com morbidades e mortalidade ap?s cinco anos de seguimento. Metodologia : um estudo de coorte hist?rica foi realizado com pacientes que freq?entaram o servi?o ambulatorial no per?odo de janeiro a dezembro de 1998, com idade > 60 anos. Na primeira etapa, o prontu?rio dos referidos pacientes foi extensamente revisado, identificando-se pacientes com s?ndrome metab?lica (SM), morbidades e estilo de vida. Na segunda etapa, foi realizado contato telef?nico com os pacientes e/ou seus familiares para a obten??o da informa??o de ocorr?ncia de ?bito no per?odo, e sua poss?vel causa. An?lise estat?stica descritiva, comparativa e multivariada foi realizada, bem como foi calculada a curva de sobreviv?ncia calculada por Cox e Kaplan-Meier. Resultados : de um total de 383 pacientes idosos que freq?entaram o ambulat?rio no per?odo investigado, foram contatados 283 (73,9%). Compara??o entre a amostra contatada e a perdida n?o mostrou diferen?as entre as mesmas, sugerindo-se que tal perda n?o implicaria em um vi?s na amostra. Os principais resultados obtidos incluiram a observa??o de: (1) uma preval?ncia de SM de 26,5% (75); (2) uma mortalidade no per?odo de seguimento de 5,3% (15) dos idosos investigados, sendo que apenas um idosos com SM faleceu no per?odo; (3) no grupo afetado al?m das morbidades associadas ao diagn?stico (hipertens?o, diabetes, obesidade e dislipidemia) as seguintes outras doen?as foram significativamente associadas a SM: infarto agudo do mioc?rdio e angina est?vel. Ao contr?rio das outras morbidades, osteoporose foi inversamente associada a SM; (4) dado o n?mero reduzido de indiv?duos que foram a ?bito, n?o foi observada associa??o entre SM e mortalidade no per?odo investigado. Conclus?o : Apesar da n?o associa??o com mortalidade, a maioria dos resultados obtidos em rela??o a SM est?o em concord?ncia com a literatura e sugerem ser tal doen?a de grande impacto na cl?nica geri?trica.

Made available in DSpace on 2015-04-14T13:35:55Z (GMT). No. of bitstreams: 1 457609.pdf: 908457 bytes, checksum: 4face2ee7aed14459bb47a89ca31f82a (MD5) Previous issue date: 2013-11-29 / Background: The current study aims to test and a vancomycin protocol based on the initial hemodialysis patients weight and to describe drug peak and through serum levels. Methods: A study enrolling 16 ESRD adult patients cohort undergoing hemodialysis received a uniform vancomycin administration schedule: 20 mg/kg initial dose, infused during the last dialysis hour; blood sample collection 30 minutes post-dialysis and, subsequently, before every dialysis session. Additionally, a fixed schedule to adjust every new dose was used. Anthropometric, clinical and laboratory variables were collected. Descriptive statistics was used; Spearman correlation coefficient was used to verify associations. Results: No significant correlation between vancomycin peak serum level and trough levels and the initial dose, nor any trough level and the following doses were uncovered. However, total serum protein strong and positively correlated with the initial Vancomycin dose and the first trough serum level (rs = 0.608, P = 0.016 and rs= 0.641; P = 0.010, respectively). Initial dose positively correlated with albumin too (rs= 0.572, P = 0.02). A strong correlation between the first and second trough levels was also found (rs = 0.608; P = 0.021). Conclusion: As applied, the vancomycin administration protocol was ineffective in reaching and maintaining therapeutic peak and trough levels. It is possible that a significant loss of vancomycin free-fraction by dialysis accounted for such a finding. Correlation of vancomycin serum levels between total serum proteins should be further investigated. / Objetivo Descrever os n?veis s?ricos de vancomicina em amostras coletadas nos vales em pacientes em hemodi?lise, a partir de um protocolo de administra??o deste antimicrobiano com dose inicial de 20mg/kg seguida de 10mg/kg e ajustes nas doses subsequentes, conforme a faixa de vancocinemia obtida e correlacionar com par?metros fisiol?gicos para verificar poss?veis associa??es. M?todos Estudo de coorte onde foram inclu?dos pacientes em hemodi?lise ambulatorial, com idade igual ou superior a 18 anos que realizaram tratamento com vancomicina, emp?rico ou com germe isolado. O medicamento foi administrado por infus?o intravenosa numa concentra??o de 10mg/mL na ?ltima hora da sess?o de hemodi?lise. O protocolo proposto baseia-se em doses administradas a cada sess?o de di?lise, realizadas tr?s vezes na semana, considerando o peso do paciente, uma dose inicial e define ajustes de dose a cada vancocinemia, com o objetivo de mant?-la nos n?veis terap?uticos estabelecidos de 10 a 20mg/L. Resultados: N?o houve correla??o significativa entre as concentra??es de vancomicina s?rica no pico e vales com as doses definidas pelo protocolo. Entretanto, o primeiro vale e as prote?nas plasm?ticas apresentaram forte correla??o positiva (rs = 0.608, P = 0.01), al?m da dose inicial tamb?m se correlacionar positivamente com as prote?nas plasm?ticas e albumina (rs = 0.641, P = 0.01 e rs= 0.572, P = 0.02). Os n?veis s?ricos de vancomicina entre o primeiro e o segundo vales apresentam forte correla??o positiva (rs = 0.608, P = 0.02) e o volume de distribui??o apresenta forte correla??o inversa ao valor de pico de vancomicina (rs = - 0.990; P < 0.001). Conclus?o Embora o estudo n?o tenha sido capaz de determinar um protocolo, identificamos uma variabilidade muito grande entre os resultados de vancocinemia. Doses mesmo ajustadas pelo peso seco do paciente e n?veis s?ricos de vancomicina n?o foram suficientes para manter os n?veis terap?uticos de vancomicina. ? poss?vel que haja perda significativa de vancomicina durante a hemodi?lise. A correla??o com as prote?nas plasm?ticas pode ser sugestiva quanto ? prote??o na remo??o durante a di?lise, por?m necessita ser investigada.

Made available in DSpace on 2015-04-14T13:35:55Z (GMT). No. of bitstreams: 1 457603.pdf: 4114697 bytes, checksum: 30488d5fc2e6e62e5cc39c6a00ca84ff (MD5) Previous issue date: 2014-02-21 / Objective: To evaluate the association of leptin levels in the maternal plasma, umbilical cord plasma and placental tissue of normotensive and preeclamptic (PE) pregnant women. Patients and methods: Leptin levels were analysed in the maternal plasma, umbilical cord plasma and placental tissue of 50 women with preeclampsia and 67 normotensive pregnant women. Plasma and placental leptin were measured using the MagPlexTH-C microspheres system. Results: Leptin levels were 40 times higher in the maternal plasma and 82 times higher in the placental tissue of patients with preeclampsia in comparison to the controls. The geometric means found were 19.59 ng/mL and 163.31 mg/g in the PE group, and 13.96 ng/mL and 89.95 mg/g in the normotensive group, respectively. Analysis of the umbilical cord plasma showed no significant difference between the groups. The mean ratios found after adjustment for maternal age, BMI and gestational age were: maternal plasma (MR=1.40; 95% CI: 1.00 - 1.97, p=0.049), fetal plasma (MR=1.33; 95% CI: 0.85- 2.09, p=0.216) and placenta (MR=1.82; 95% CI: 1.11 - 2.98, p=0.019). Conclusion: Leptin values found in patients with preeclampsia are significantly increased in maternal plasma and placental tissue in comparison to the control. The extremely high levels in the placenta are believed to have resulted from studies that specifically aimed to evaluate biomarkers. / Objetivo: Avaliar a associa??o dos n?veis de leptina no plasma materno, plasma do cord?o umbilical e tecido placent?rio de gestantes normotensas e com pr?-ecl?mpsia (PE). Pacientes e m?todos: Foram analisados os n?veis de leptina no plasma materno, plasma do cord?o umbilical e tecido placent?rio de 50 gestantes com pr?-ecl?mpsia e 67 gestantes normotensas. A leptina foi mensurada em plasma e placenta utilizando o Sistema MagPlexTH-C - ensaio de microesferas.Resultados: Os n?veis de leptina foram 40 vezes maiores no plasma materno e 82 vezes maiores no tecido placent?rio das pacientes pr?-ecl?mpticas em compara??o aos controles. No grupo Pr?-ecl?mpsia encontramos as m?dias geom?tricas de 19.59 ng/mL e 163.31 mg/g e nas normotensas 13.96 ng/mL e 89.95 mg/g respectivamente. A an?lise do plasma do cord?o umbilical n?o mostrou diferen?a significativa entre os grupos. As raz?es das m?dias encontradas ap?s ajuste para idade materna, ?ndice de massa corporal e idade gestacional, foram no plasma materno (rm=1.40; IC 95%: 1.00 - 1,97, p=0.049), no plasma fetal (rm=1.33; IC 95%: 0.85- 2.09, p=0.216) e na placenta (rm=1.82; IC 95%: 1.11 - 2,98, p=0.019). Conclus?o: Os valores de leptina encontrados nas pacientes com pr?-ecl?mpsia quando comparados ao controle s?o significativamente maiores no plasma da m?e e no tecido placent?rio. Os n?veis extremamente elevados na placenta s?o sugestivos de estudos com desenho espec?fico para investiga??o de biomarcador.