Made available in DSpace on 2015-04-14T13:35:43Z (GMT). No. of bitstreams: 1 449076.pdf: 2149864 bytes, checksum: 436715bc4f609c1ff745767ad8aaf555 (MD5) Previous issue date: 2013-03-25 / Introduction: It has been recently shown that enriched environment leads to a significant benefit in learning and retention of visual-spatial memory, being able to reverse the cognitive impairment generated by undernourishment and seizures. Considering the role of the hippocampus in memory/learning, we investigated the effects of the enriched environment on hippocampal morphometry of rats submitted to recurrent seizures and undernourishment in the neonatal period. Methods: Male offspring of rats were allocated on 8 experimental groups Nourished controls (N), Nourished with Recurrent Seizures (N + RS), Nourished with Enriched Environment (N + EE); Nourished with Recurrent Seizures and Enriched Environment (N + RS + EE), Undernourished Controls (U), Undernourished with Convulsive Crisis (U + CC), Undernourished with Enriched Environment (U + EE); Undernourished with Recurrent Seizures and Enriched Environment (U + RS + EE). Undernourished groups were maintained on a regimen of food deprivation by progressive removal of the second lactating female (P2) to the fifteenth (P15), an increase of 2 hours a day up to a total 12 hours, which was kept maximum spacing until end undernourishment. Between P8 and P10, groups with recurrent Seizures were exposed to three recurrent seizures per day induced by flurothyl. Between P21 and P51 all animals with an enriched environment were exposed to it. At P51 all animals were sacrificed by transcardiac perfusion. We evaluated the volume of the hippocampus using the grid points methodology. Neuronal and glial densities, hippocampal volume and CA1 subfield thickness were calculated based on the two-dimensional quantitative system for test points created by Image Pro Plus 6.0 software (Media Cybernetics Capture, USA). Results: Undernourisment during early development decreased neuronal density in the CA1 and CA3 subfield, as well as in the glial density in CA1 subfield. In parallel, recurrent seizures promoted a decrease in the glial density in CA1 and CA3 area. The animals submitted to the enriched environment show an increased hippocampal volume and thickness of layer of CA1. Conclusions: Pathological findings, with onset in the early stages of undernourishment and epilepsy may be a significant factor in comorbidities, such as cognitive dysfunction found in patients with epilepsy and malnutrition. Taking these findings together, we can assume that environment stimulation beginning early in life may play a critical role in improving the structural brain development and hence cognitive functioning. / Introdu??o: Recentemente mostrou-se que o enriquecimento ambiental promove significativa melhora na aprendizagem e reten??o de mem?ria visual-espacial, sendo capaz de reverter a disfun??o cognitiva gerada por subnutri??o e crises convulsivas. Considerando o papel do hipocampo na mem?ria/aprendizagem, investigamos os efeitos do ambiente enriquecido sobre a morfometria do hipocampo de ratos submetidos a crises recorrentes e desnutri??o no per?odo neonatal. M?todos: Filhotes machos de ratos Wistar foram alocados em 8 grupos: Nutridos Controles (N), Nutridos com Crise Convulsiva (N+CC), Nutridos com Ambiente Enriquecido (N+AE); Nutridos com Crises convulsiva e Ambiente Enriquecido (N+CC+AE), Desnutridos Controles (D), Desnutridos com Crise Convulsiva (D+CC), Desnutridos com Ambiente Enriquecido (D+AE); Desnutridos com Crises convulsiva e Ambiente Enriquecido (N+CC+AE). Os animais dos grupo desnutridos foram mantidos em um regime de priva??o alimentar progressivo por afastamento da f?mea nutriz do segundo (P2) ao d?cimo quinto (P15), aumentando 2 horas por dia at? totalizar 12 horas, per?odo m?ximo que foi mantido o afastamento at? o fim da desnutri??o. Entre P8 e P10, os grupos com crises convulsivas foram expostos diariamente a tr?s crises recorrentes induzidas por flurotil. Entre P21 e P51 os animais dos com ambiente enriquecido foram expostos ao mesmo. Em P51 todos animais foram sacrificados por perfus?o Transcard?aca. Foi avaliado o volume do Hipocampo atrav?s da metodologia de grade de pontos. As densidades neuronais e gliais nas subregi?es CA1 e CA3 e a espessura da subregi?o CA1 foram calculadas a partir do sistema quantitativo bidimensional, por teste de pontos criado pelo software Image Pro Plus 6.0 (Capture Media Cybernetics, USA). Resultados: A desnutri??o durante o desenvolvimento inicial reduziu a densidade neuronal nos subregi?es CA1 e CA3, bem como promoveu uma diminui??o na densidade de c?lulas gliais em CA1. Em paralelo, as crises convulsivas promoveram uma diminui??o na densidade de c?lulas gliais em CA1 e CA3. Os animais submetidos ao ambiente enriquecido apresentaram um aumento de volume do hipocampo e da espessura da camada de CA1. Conclus?es: Os achados do presente estudo sugerem que a estimula??o ambiental no in?cio da vida pode desempenhar um papel fundamental na melhoria do desenvolvimento estrutural do c?rebro e, consequentemente, do seu funcionamento cognitivo.

Made available in DSpace on 2015-04-14T13:35:43Z (GMT). No. of bitstreams: 1 449044.pdf: 1199150 bytes, checksum: e72525b4664138d94dbc977a6745627e (MD5) Previous issue date: 2013-03-25 / Introduction: Septic shock is one of the greatest health problems worldwide, affecting millions of people a year. It presents as a continuum of infectious events and interactions between pathogens caused by the relationship between apoptotic, anti-inflammatory and inflammatory mediators, generating tissue hypoxia, hypovolemia, and increased oxidative stress. Respiratory physiotherapy can help increase oxygenation and improve gas exchanges. The purpose of this study was to evaluate the immediate effect of respiratory physiotherapy on hemodynamic, metabolic, inflammatory and oxidative stress parameters in patients with septic shock. Methods: Before and after quasi-experimental study in thirty patients in septic shock, who underwent respiratory physiotherapy, without associated heart diseases and with vasopressors less than 0.5 mL/Kg/min. Venous and arterial blood gas, clinical and hemodynamic data, inflammatory data, lactate and oxidative stress were evaluated before and 15 minutes after physiotherapy. Results: Thirty patients with a mean age of 61.77?15.91 years and SOFA of 7.9?3.1 were included. Respiratory physiotherapy caused a reduction of pH (p=0.003), PaCO2 (p=0.009), lactate (p=0.0002) and TBARS (p=0.04) and an increase of PaO2 (p=0.026), SaO2 (p=0.018) and PaO2/FiO2 (p=0.04) ratio, 15 minutes after it was applied. Conclusion: The results indicate that respiratory physiotherapy has immediate effects, improving oxygenation, reducing lactate and oxidative damage in patient in septic shock. However, it does not cause alterations in the inflammatory and hemodynamic parameters. / Introdu??o: O choque s?ptico ? um dos maiores problemas de sa?de no mundo, afetando milh?es de pessoas a cada ano. Ele se apresenta como uma continuidade de eventos infecciosos e intera??es entre pat?genos causadas pela rela??o entre mediadores apopt?ticos, anti-inflamat?rios e inflamat?rios, gerando hip?xia tecidual, hipovolemia e aumento do estresse oxidativo. A fisioterapia respirat?ria pode promover aumento da oxigena??o e melhora das trocas gasosas, oferecendo uma demanda de oxig?nio ? via aer?bica. Objetivos: Avaliar o efeito imediato da fisioterapia respirat?ria sobre os par?metros hemodin?micos, metab?licos, inflamat?rios e de estresse oxidativo em pacientes com choque s?ptico. M?todos: Estudo quasi-experimental, do tipo antes e depois. Foram inclu?dos pacientes com choque s?ptico e que realizaram fisioterapia respirat?ria, sem cardiopatias associadas e com vasopressores inferiores a 0,5 mL/Kg/min. Foram avaliados gasometria venosa e arterial, dados cl?nicos e hemodin?micos, inflamat?rios, lactato e estresse oxidativo antes e 15 minutos ap?s a fisioterapia. Resultados: Participaram do estudo 30 pacientes com m?dia de idade de 61,77?15,91 anos e SOFA de 7,9?3,1. A fisioterapia respirat?ria provocou uma diminui??o na pH (p=0,003), PaCO2 (p=0,009), lactato (p=0,0002) e TBARS (p=0,04) e aumento na PaO2 (p=0,026), SaO2 (p=0,018) e rela??o PaO2/FiO2 (p=0,04) 15 minutos ap?s a sua aplica??o. Conclus?o: Os resultados indicam que a fisioterapia respirat?ria provoca efeitos imediatos, melhorando a oxigena??o, diminuindo o lactato e o dano oxidativo em pacientes com choque s?ptico, por?m sem provocar altera??es nos par?metros inflamat?rios e hemodin?micos

Made available in DSpace on 2015-04-14T13:35:43Z (GMT). No. of bitstreams: 1 449047.pdf: 1220829 bytes, checksum: 33f8d43136b68cb4835635004e1f6dfc (MD5) Previous issue date: 2013-03-25 / Background: The gastric bypass surgery is one of the most used worldwide for the treatment of obesity and there is no consensus on the ideal size of intestinal loops in gastric bypass of bariatric surgeries. This study assessed the metabolic outcome of patients submitted to gastric bypass with alimentary and biliopancreatic loops of different sizes. Materials and Methods: We conducted a retrospective cohort study in diabetic obese patients (BMI ≥35 kg/m2) with metabolic syndrome submitted to gastric bypass. The patients were divided into 3 groups according to the size of the intestinal loop: group 1, biliopancreatic loop of 50 cm and alimentary loop of 100 cm; group 2, biliopancreatic loop of 50 cm and alimentary loop of 150 cm; and group 3, biliopancreatic loop of 100 cm and alimentary loop of 150 cm. The effect of gastric bypass with different sizes of intestinal loops in relation to the parameters that define metabolic syndrome according to IDF was determined. The postoperative periods evaluated were: 3, 6, 12 and 24 months Results: Sixty-three patients were evaluated, and they had a mean age of 44.7?9.4 years; 62 (98.4%) were hypertensive and 51 (82.2%) dyslipidemic. The 3 groups studied were homogeneous in relation to the variables studied. In 24 months, there was a remission of systemic arterial hypertension in 65% of patients in group 1, 62.5% in group 2 and 68.4% in group 3. Remission of DM2 occurred in 85% of patients in group 1, 83% in group 2 and 84% in group 3. There was no statistical difference in %LEW between the groups, and waist measurements decreased in a homogeneous way in all groups. The size of loops also had no influence on the improvement in dyslipidemia. Conclusion: Variation in size of intestinal loops does not appear to influence improvement in metabolic syndrome in this group of patients. / Objetivo: O bypass g?strico ? uma das cirurgias mais utilizadas no mundo para o tratamento da obesidade e n?o h? consenso sobre o tamanho ideal das al?as intestinais na confec??o desta t?cnica. Propomos um estudo para avaliar os desfechos metab?licos destes pacientes submetidos ao bypass g?strico com al?a intestinal alimentar e biliopancre?tica de tamanhos diferentes. M?todos: Realizamos uma coorte retrospectiva, em pacientes obesos (IMC ≥35Kg/m2) diab?ticos com s?ndrome metab?lica submetidos ao bypass g?strico. Os pacientes foram divididos em 3 grupos conforme a dimens?o das al?as intestinais: grupo 1, al?a biliopancre?tica de 50 cm e al?a alimentar de 100 cm; grupo 2, al?a biliopancre?tica de 50 cm e al?a alimentar de 150 cm; grupo 3, al?a biliopancre?tica de 100 cm e al?a alimentar de 150 cm. Foi avaliado o efeito do bypass g?strico com dimens?es diferentes de al?as intestinais em rela??o aos par?metros que comp?em a s?ndrome metab?lica conforme a IDF. Os per?odos p?s-operat?rios avaliados foram: 3, 6, 12 e 24 meses. Resultados: Foram avaliados 63 pacientes, sendo 48 (76%) do sexo feminino. A m?dia de idade foi de 44.7?9.4 anos; 62 pacientes (98.4%) eram hipertensos e 51 (82.2%) dislipid?micos. Os 3 grupos estudados eram homog?neos em rela??o ?s vari?veis estudadas, P>0,05. Em 24 meses houve remiss?o da HAS em 65% dos pacientes do grupo 1, 62.5% no grupo 2 e 68.4% (P>0,05). A remiss?o do DM2 ocorreu em 85% dos pacientes do grupo 1, 83% no grupo 2, e 84% no grupo 3 (P >0.05). N?o houve diferen?a estat?stica na %PEP entre os grupos e as medidas da circunfer?ncia abdominal reduziram de forma homog?nea em todos os grupos (P>0,05), mas apenas 3% alcan?aram medidas abaixo dos crit?rios sugeridos pelo IDF. A redu??o m?dia dos triglicer?deos e a perman?ncia abaixo de 150 mg/dL ocorreu em 80% no grupo 1, 64,3% grupo 2 e 76,9% no grupo 3 (P>0,05). Houve aumento do HDL nos 3 grupos e n?o houve diferen?a estat?stica na compara??o dos grupos. Conclus?o: A varia??o da dimens?o das al?as intestinais parece n?o influenciar na melhora da s?ndrome metab?lica, entretanto n?o h? consenso do tamanho ideal das al?as intestinais no bypass g?strico.

Made available in DSpace on 2015-04-14T13:35:44Z (GMT). No. of bitstreams: 1 448169.pdf: 585932 bytes, checksum: bc32e87177240a56313222cf3240e579 (MD5) Previous issue date: 2013-03-18 / Background: The prevalence of smoking habits in the morbidly obese is higher than in the general population. There is some evidence that smokers have different temperaments compared to non-smokers. Methods: We analyzed data on affective and emotional temperament assessed by the AFECTS scale in a cross-sectional survey of bariatric surgery candidates, 18-65 years old, with class II and III obesity, recruited and grouped in smokers, ex-smokers, and non-smokers. Results: No significant differences were detected in affective and emotional temperament with respect to smoking status among 420 bariatric surgery candidates (74.5% females, 92.9% Caucasian and mean BMI of 45.9?7.6 kg/m2), except in patients without current psychiatric diagnosis or psychiatric medication. In these cases, smokers had higher scores in anxious than ex-smokers (median 3[2-4] percentile; median 2[1-4] percentile; P=0.007) and non-smokers (median 3[2-4] percentile; median 2[1-4] percentile P=0.005), and lower scores in control than non-smokers (39,7?11,2; 44,1?9,8; P=0.032), while ex-smokers scored higher in hyperthymic than non-smokers (median 4[4-5] percentile; median 3[2-4] percentile P=0.012). When the groups were stratified for BMI of 35-45 kg/m?, smokers had higher scores in euphoric than ex-smokers (median 3[2-5] percentile; median 2[1-3] percentile; P=0.034), while ex-smokers scored higher in dysphoric than non-smokers (median 3[2-4] percentile; median 2[1-4] percentile; P=0.042). Ex-smokers with BMI >50 kg/m? scored higher on coping (P=0.034) and control (P=0.029) than smokers when adjusted for age and sex. Dysphoric and euphoric temperaments was associated with light smokers (median 3[2-4] percentile; median 2[1-3] percentile; P=0,009; median 3[1-4] percentile; median 2[1-3] percentile; P=0.035). Conclusions: Smoking in bariatric surgery candidates was associated with lower control, higher anxiety and euphoric temperaments. Light smokers were associated with higher dysphoric and euphoric temperaments. Assessment of temperament in bariatric surgery candidates may help in decisions about smoking cessation treatment and prevention of smoking relapse after surgery. / INTRODU??O: Estimativas de preval?ncia de tabagismo em obesos m?rbidos tem sido maiores que na popula??o em geral. Existem algumas evid?ncias de que tabagistas possuem temperamentos distintos de n?o tabagistas. OBJETIVO: Avaliar a ocorr?ncia de dimens?es de temperamentos na popula??o que se candidata a realiza??o de cirurgia bari?trica e verificar se h? diferen?as entre fumantes, exfumantes e n?o fumantes. M?TODOS: Foram analisados dados sobre o temperamento afetivo e emocional atrav?s da escala AFECTS em um estudo transversal de candidatos ? cirurgia bari?trica entre 18-65 anos de idade, graus II e III de obesidade, recrutados e agrupados de acordo com seu status tab?gico (fumantes, ex-fumantes e n?o fumantes). RESULTADOS: N?o foram detectadas diferen?as estatisticamente significativas nos temperamentos afetivos e emocionais em rela??o ao status tab?gico entre os 420 candidatos ? cirurgia bari?trica (74,5% sexo feminino, 92,9% brancos e m?dia de IMC 45,9?7,6 Kg/m2). Ao se excluir pacientes sem diagn?stico psiqui?trico atual (n=228) e sem medica??o psiqui?trica (n= 325), o grupo de fumantes apresentou escores mais altos de temperamento ansioso do que os ex-fumantes (mediana 3[2-4] percentil; mediana 2[1-4] percentil; P=0,007) e os n?o-fumantes (mediana 3[2-4] percentil; mediana 2[1-4] percentil; P=0,005), e escores mais baixos em Controle do que os n?o-fumantes (39,7?11,2; 44,1?9,8; P=0,032). J? os exfumantes tiveram escores mais elevados no temperamento hipert?mico do que os n?ofumantes (mediana 4[4-5] percentil; mediana 3[2-4] percentil; P=0,012). Quando os grupos foram estratificados por IMC, entre 35-45kg/m? os fumantes apresentaram escores mais altos no temperamento euf?rico do que os ex-fumantes (mediana 3[2-5] percentil; mediana 2[1-3] percentil; P=0,034), enquanto ex-fumantes tiveram escores mais elevados no temperamento disf?rico do que os n?o-fumantes (mediana 3[2-4] percentil; mediana 2[1-4] percentil; P=0,042). Em pacientes com IMC acima de 50 kg/m?, quando ajustado para idade e sexo, exfumantes tiveram escores mais elevados em Enfrentamento (P=0,034) e Controle (P=0,029) do que os fumantes. Os temperamentos disf?rico e euf?rico foram associados com fumantes leves em rela??o a fumantes pesados (mediana 3[2-4] percentil; mediana 2[1-3] percentil; P=0,009; mediana 3[1-4] percentil; mediana 2[1-3] percentil; P=0,035, respectivamente). Conclus?o: Fumar em obesos candidatos a cirurgia bari?trica foi associado com baixo Controle e escores elevados nos temperamentos ansioso e euf?rico. Fumar menos de dez cigarros ao dia foi associado com os temperamentos disf?rico e euf?rico. A avalia??o do temperamento em candidatos a cirurgia bari?trica permite nos ajudar a tomar decis?es sobre a individualiza??o do tratamento e preven??o de reca?da do tabagismo ap?s a cirurgia.

Made available in DSpace on 2015-04-14T13:35:45Z (GMT). No. of bitstreams: 1 450246.pdf: 1514408 bytes, checksum: 6ceddb0f6677e9485ec44236c23b7b0b (MD5) Previous issue date: 2013-03-25 / The spinal cord injury (SCI) is a condition that dramatically affects the quality of life of affected patients, has a high incidence and causes a high cost to the government and society. Existing treatments for SCI are only palliative nature, not being able to reverse the neurological damage caused by trauma. As a result, it is necessary to investigate new therapies that seek more effective solutions for these cases. The studies with bone marrow mononuclear cells (BMMC) have shown encouraging results, but still not definitive for clinical application, so the expansion of preclinical studies is essential. In this study we aimed to compare treatment outcomes between groups with 3 and 5 applications BMMC applications, analyzing motor function, and inflammation at the lesion site after treatment with BMMC by subarachnoid through via lumbar puncture. The experimental groups were divided into two groups, with different times of transplantation. A group of 3 applications of BMMC, the first application 48 hours, 9 days and 16 days after SCI and a second group with 5 BMMC applications, application in the first 48 hours, 9, 16, 23 and 30 days after by spinal cord injury. The BMMC of male wistar rats was applied via subarachnoid. The entire group received vehicle (saline). The animals were evaluated for motor function through the BBB scale, for the presence of BMMC in the lesion by PCR for the presence of Y chromossome of the cells, and the inflammatory process at the site of injury, analyzing IL-1β and TNF-α, by immunohistochemistry. Our results show an improvement in motor function in the groups treated with BMMC transplants. The immunohistochemical evaluation revealed no difference in the expression of inflammatory cytokines Il-1β and TNF-α at the site of injury in the groups treated with BMMC. The PCR analysis for the presence of chromossome of the cells was negative at the 37th day of the last application of BMMCs / O trauma-raquimedular (TRM) ? uma patologia que afeta drasticamente a qualidade de vida dos pacientes acometidos, apresenta alta incid?ncia e ocasiona um alto custo para o governo e a sociedade. Os tratamentos existentes para o TRM s?o apenas de cunho paliativo, n?o sendo capazes de reverter o dano neurol?gico ocasionado pelo trauma. Em fun??o disso, ? necess?rio investigar novas terapias que busquem solu??es mais efetivas para esses pacientes. Os estudos com c?lulas-tronco de medula ?ssea (CMMO) t?m demonstrado resultados animadores, mas ainda n?o definitivos para aplica??o cl?nica; assim, a amplia??o dos estudos pr?-cl?nicos ? indispens?vel. Neste estudo tivemos o objetivo de comparar os resultados do tratamento de CMMO pela via subaracnoidea (VS) atrav?s de pun??o lombar (PL), entre grupos com 3 aplica??es e 5 aplica??es de CMMO, analisando a fun??o motora e o processo inflamat?rio no local da les?o. Nossos grupos experimentais de estudo foram divididos em 2 grupos pela via de administra??o subaracn?idea, com tempos de transplante diferentes. Um grupo com 3 aplica?oes de CMMO, sendo a primeira aplica??o em 48h, 9 dias e 16 dias ap?s a les?o medular (LM) e um segundo grupo com 5 aplica??es de CMMO, primeira aplica??o em 48 h, 9, 16, 23 e 30 dias ap?s a Les?o Medular (LM) pela VS e cada grupo com seu controle de ve?culo, solu??o salina (SS). Os animais doadores eram machos e os receptores eram f?meas. As ratas foram avaliadas quanto ? fun??o motora, atrav?s da escala de Basso, Beattie and Bresnahan (BBB), quanto ? presen?a de CMMO na les?o, por meio da Rea??o em Cadeia da Polimerase (PCR) para a detec??o do cromossomo Y dos animais doadores, e quanto ao processo inflamat?rio no local da les?o, analisando a interleucina 1 beta (IL-1β) e o fator de necrose tumoral alfa (TNF-α), atrav?s de imuno-histoquimica. Nossos resultados demonstraram uma melhora da fun??o motora nos grupos tratados com transplantes de CMMO, sendo mais r?pida nos animais que receberam 7 cinco aplica??es. A avalia??o imuno-histoqu?mica revelou que n?o houve diferen?a na express?o das citocinas inflamat?rias IL-1β e TNF-α no local da les?o nos grupos tratados com CMMO. A an?lise de PCR n?o demonstrou c?lulas no local da les?o, quando analisadas no 37? dia

Made available in DSpace on 2015-04-14T13:35:46Z (GMT). No. of bitstreams: 1 450447.pdf: 3645797 bytes, checksum: abdc582487fc7c81fd903cc19cb4f28a (MD5) Previous issue date: 2013-03-25 / Objective: to evaluate the expression of AMP-activated protein kinase (AMPK) and Sirtuin-1 (SIRT-1) in liver tissue samples from patients during bariatric surgery and one year after the procedure. To evaluate the association between the expression of these proteins with weight, Body Mass Index (BMI) and biochemical parameters (glucose, total cholesterol, HDL and triglycerides). Methods: the expression of the proteins was verified by immunohistochemistry and quantified by digital image analysis. All other data were accessed in the database. Results: liver biopsies of 44 patients submitted to bariatric surgery were analyzed. 31 (70.5%) were women and 13 (29.5%) were men. The mean age was 37.18 ? 11.26 years. The mean preoperative weight was 127.29 ? 27.10kg, decreasing to 82.00 ? 19.94kg postoperatively. With this significant reduction, the mean BMI also reduced by removing the patient's classification from obesity grade III to overweight. The mean biochemical parameters also showed significant improvement, with the exception of HDL, which showed no significant change. SIRT-1 expression had a mean value of 128.80μm2 in the intraoperative biopsies and 306.68μm2 in the biopsies performed one year after (p = 0.0069). And AMPK had mean values of 4166.10μm2 and 2718.70μm2 respectively (p = 0.0028). Conclusion: the present study showed an increased expression of SIRT-1 and a decrease in the expression of AMPK in postoperative liver biopsies. This pattern of expression accompanied improvements in weight, BMI and the profile of biomarkers that are associated with the development of co-morbidities also verified one year after surgery. / Objetivo: avaliar a express?o da prote?na quinase ativada por AMP (AMPK) e sirtuina-1 (SIRT-1) em amostras histol?gicas hep?ticas de pacientes no transoperat?rio e um ano ap?s a realiza??o da cirurgia bari?trica. Avaliar a associa??o entre a express?o dessas prote?nas com o peso, ?ndice de Massa Corporal (IMC) e par?metros bioqu?micos (glicose, colesterol total, HDL e triglicer?deos). Metodologia: a express?o das prote?nas foi verificada atrav?s de imunoistoqu?mica e quantificada por m?todo de microscopia por an?lise de imagem digital. As demais informa??es foram acessadas em banco de dados. Resultados: as bi?psias hep?ticas de 44 pacientes submetidos ? cirurgia bari?trica foram analisadas. 31 (70.5%) eram de mulheres e 13 (29.5%) eram de homens. A m?dia de idade foi de 37.18 ? 11.26 anos. A m?dia do peso pr?-operat?rio foi de 127.29 ? 27.10kg, reduzindo para 82.00 ? 19.94kg no p?s-operat?rio. Com essa redu??o significativa, o IMC m?dio tamb?m reduziu, retirando os pacientes da classifica??o de obesidade grau III para sobrepeso. As m?dias dos par?metros bioqu?micos tamb?m apresentaram melhora importante, com exce??o do HDL, que n?o teve altera??o significativa. Em rela??o ? SIRT-1 foram encontradas m?dias de 128.80μm2 nas bi?psias do transoperat?rio e de 306.68μm2 nas bi?psias realizadas um ano ap?s (p= 0.0069). J? a AMPK teve m?dias de 4166.10μm2 e 2718.70μm2, respectivamente (p=0.0028). Conclus?o: a express?o da SIRT-1 aumentou e a da AMPK diminuiu nas bi?psias hep?ticas p?s-operat?rias, ambas de forma significativa. O padr?o de express?o encontrado acompanhou os resultados de melhorias no peso, IMC e perfil de biomarcadores que s?o associados ao desenvolvimento de co-morbidades, verificados tamb?m verificados ap?s o per?odo de um ano.

Made available in DSpace on 2015-04-14T13:35:47Z (GMT). No. of bitstreams: 1 450585.PDF: 3679647 bytes, checksum: 449520a022e29d4951604d60809e331f (MD5) Previous issue date: 2013-08-09 / Attention deficit/hyperactivity disorder (ADHD) is one of the most prevalent neuropsychiatric disorders among children. Although the clinical presentation and treatment of ADHD are well established, its etiology is not yet known. Recent functional neuroimaging techniques may help increase knowledge about the pathophysiology of the disorder, allowing for the empirical testing of theoretical hypotheses on brain networks in ADHD. In this study, we analyzed a group of 23 treatment na?ve boys with ADHD, aged between 8 and 10 years old, who underwent a protocol of resting-state functional magnetic imaging before and after six months of treatment with methylphenidate. Analyses of functional connectivity were performed between regions of interest (seeds) placed within the default mode network (DMN). Subsequently, changes in the DMN connectivity before and after treatment were investigated with an independent component analysis (ICA). Results of the seeds analysis showed no significant changes in connectivity between regions of the DMN following treatment, with a relatively small increase in the anterior-posterior connectivity of the network. The ICA revealed a significant increase in the connectivity between the left putamen and the DMN (p <0.01, corrected). There was also a positive correlation between the decrease of symptoms and the connectivity between the putamen and the DMN after treatment (rho = 0.65, p = 0.17). These findings indicate that treatment with methylphenidate modifies the connectivity between the DMN and subcortical nuclei. Dysfunctions in corticalsubcortical circuits have often been associated with the pathophysiology of ADHD. The effect of treatment with methylphenidate may in part be associated with elevated dopamine levels in subcortical nuclei, modulating its connectivity with the DMN. / O transtorno de d?ficit de aten??o/hiperatividade (TDAH) ? um dos transtornos neuropsiqui?tricos mais prevalentes entre crian?as. Embora a apresenta??o cl?nica e o tratamento do TDAH estejam bem estabelecidos, suas causas ainda n?o s?o conhecidas. T?cnicas recentes de neuroimagem funcional podem ampliar o conhecimento acerca da fisiopatologia do transtorno, permitindo a testagem emp?rica de hip?teses conceituais sobre o funcionamento de redes cerebrais no TDAH. Neste trabalho, analisamos um grupo de 23 meninos com diagn?stico de TDAH, com idades entre 8 e 10 anos, virgens de tratamento, que foram submetidos a um protocolo de resson?ncia funcional de repouso antes e ap?s seis meses de tratamento com metilfenidato. Foram realizadas an?lises de conectividade funcional entre regi?es de interesse (seeds) demarcadas sobre ?reas da rede default mode network (DMN). Posteriormente, a conectividade da DMN antes e ap?s o tratamento foi mapeada atrav?s de uma an?lise de componentes independentes (ICA, independent component analysis). Os resultados da an?lise de seeds n?o demonstraram modifica??es significativas na conectividade entre regi?es da DMN com o tratamento, havendo apenas um pequeno aumento da conectividade ?ntero-posterior da rede. A an?lise por ICA revelou um aumento significativo de conectividade da DMN com o put?men esquerdo (p<0,01 corrigido). Observou-se ainda uma correla??o positiva entre a redu??o dos sintomas e a conectividade entre o put?men e a DMN ap?s o tratamento (rho=0,65, p=0,17). Esses achados indicam que o tratamento com metilfenidato modifica a conectividade entre a DMN e n?cleos subcorticais. Disfun??es em circuitos corticosubcorticais foram frequentemente associados ? fisiopatologia do TDAH. O efeito do tratamento com metilfenidato pode, em parte, estar associado ? eleva??o dos n?veis dopamin?rgicos em n?cleos subcorticais, modulando a sua conectividade com a DMN.

Made available in DSpace on 2015-04-14T13:35:48Z (GMT). No. of bitstreams: 1 451277.pdf: 1746632 bytes, checksum: e0650e210318a78c825ed4397d3cdad3 (MD5) Previous issue date: 2013-07-12 / To meet socio-cultural demands imposed by the new millennium and its implications for education, it was necessary for teachers and students to participate actively in the teaching-learning process. In this context the course evaluation by students has been a tool widely used in various medical schools in different countries. For institutions and teachers, these assessments allow to know and measure the results, further analysis of the institutional status, review projects, adjust goals, diagnose weaknesses and correct possible deviations. For the monitoring and improvement of this process, it was necessary to create instruments that aimed to evaluate the performance of the proposed changes. Due the importance of veracity and reliability that should have this information, the search for valid and reliable instruments is essential. The present study aimed to analyze the evaluation questionnaire answered by the the undergraduate students of the Faculty of Medicine PUCRS in 2011, perform validation of the questionnaire, check the level of students satisfaction in relation to the evaluated subjects and the association among the level of satisfaction, the percentage of practical activities of the discipline, student performance and the level of absenteeism. It is cross-sectional study, exploratory and contemporary, with qualitative and quantitative evaluation. About statistics, categorical variables were described by absolute and relative frequencies, and continuous variables were described by mean and standard deviation or median and interquartile range, as the results distribution. The validity of the instrument was assessed by psychometric properties of reliability and convergent validity. 1205 responses were studied, 70.6% of students reported satisfaction with the courses taken, however a significant number of students reported dissatisfaction with assessment practices and the dynamics of the course subjects. When evaluating the convergent validity it was observed that the domain dynamics of discipline showed an association between the qualitative and quantitative questions. The reliability presented Cronbach alpha=0.753and all domains had the floor effect below 20%. The ceiling effect showed above 20% in all domanies evaluated. There was a significant association between the total score obtained by the discipline and practice workload percentage above 60%. There was no association between total score and the degree obtained and absenteeism. Stimulus should be made to ongoing training group of teachers for correction of minor routes that do not allow the enchantment of the student by course and teacher for teaching. / Para atender as demandas s?cio - culturais impostas pelo novo mil?nio e suas implica??es na educa??o, foi necess?rio que professores e alunos participassem ativamente do processo ensino-aprendizagem. Neste contexto, a avalia??o do curso pelos alunos tem sido uma ferramenta utilizada em v?rias escolas m?dicas nos diversos pa?ses. Para as institui??es e para os docentes, estas avalia??es permitem conhecer e medir os resultados obtidos, aprofundar a an?lise da realidade institucional, rever projetos, diagnosticar fragilidades adequar metas e corrigir poss?veis desvios. Para acompanhamento e aprimoramento deste processo, foi necess?ria a cria??o de instrumentos que visassem avaliar o desempenho das mudan?as propostas. Pela import?ncia da veracidade e da confiabilidade que devem ter estas informa??es, a busca de instrumentos v?lidos e confi?veis ? imprescind?vel. O presente estudo teve como objetivo geral analisar o question?rio de avalia??o das disciplinas respondido pelos alunos do curso de gradua??o da Faculdade de Medicina da PUCRS no ano de 2011, realizar a valida??o do question?rio, verificar o n?vel de satisfa??o dos alunos em rela??o ?s disciplinas avaliadas do curso e a associa??o existente entre o n?vel de satisfa??o e o percentual de atividades pr?ticas da disciplina, o desempenho do aluno e o n?vel de absente?smo. Trata-se de estudo de delineamento transversal, explorat?rio e contempor?neo, com avalia??o quali-quantitativa. Quanto ao tratamento estat?stico, as vari?veis categ?ricas foram descritas por frequ?ncias absolutas e relativas e as vari?veis continuas foram descritas mediante m?dias e desvio padr?o ou mediana e intervalo interquartil, conforme a distribui??o dos resultados. A validade do instrumento foi avaliada mediante as propriedades psicom?tricas validade convergente e confiabilidade. Foram estudadas 1205 respostas; 70,6% dos alunos referiram satisfa??o em rela??o ?s disciplinas cursadas, por?m um n?mero expressivo de alunos relatou insatisfa??o em rela??o ?s pr?ticas avaliativas e ? din?mica das disciplinas do curso. Ao avaliar a validade convergente observou-se que o dom?nio din?mica da disciplina apresentou uma associa??o entre as quest?es qualitativas e as quantitativas. A confiabilidade apresentou alfa de Cronbach =0,753 e todos os dom?nios apresentaram o efeito ch?o inferior a 20%. O efeito teto apresentou valor superior a 20% em todos os dom?nios avaliados. Houve associa??o significativa entre o escore total obtido pela disciplina e percentual de carga hor?ria pr?tica acima de 60%. N?o houve associa??o do escore total e o grau obtido e absente?smo. Est?mulo dever? ser feito para capacita??o permanente do grupo de professores para corre??o de pequenas rotas que n?o permitem o encantamento do aluno pelo seu curso e do professor pelo ensino.

Made available in DSpace on 2015-04-14T13:35:48Z (GMT). No. of bitstreams: 1 451791.pdf: 11131527 bytes, checksum: 73b1d535d96f83c30dd5fb46e7f2af5d (MD5) Previous issue date: 2013-09-11 / Tuberculosis (TB) remains a leading infectious killer and its causative agent, Mycobacterium tuberculosis, infects one third of the world population. Despite 50 years of available drug treatments, TB continues to cause considerable mortality worldwide. The TBHIV co-infection and the emergence of multidrug and extensively-resistant TB have provided a very alarming challenge to global health and led us to focus on the research for new and more effective therapeutics against the disease. Advances in the identification of new TB drug targets have been driven by the availability of the genome sequence of M. tuberculosis H37Rv, and include elucidation of the role played by proteins of essential biochemical pathways for mycobacterial growth. Inosine Monophosphate Dehydrogenase (IMPDH, EC 1.1.1.205) catalyzes the penultimate and rate-limiting step in guanine nucleotide biosynthesis, the oxidation of inosine 5 -monophosphate (IMP) to xanthosine 5 - monophosphate (XMP), with concomitant reduction of nicotinamide adenine dinucleotide (NAD+) to NADH. This reaction controls the guanine nucleotide pool and IMPDH inhibitors are used as immunosuppresive, anticancer, and antiviral agents. Recently, IMPDH from M. tuberculosis (MtIMPDH) has gained attention as a promising anti-mycobacterial target, associated with a number of distinct inhibitor scaffolds. In the present work, the guaB2- encoded MtIMPDH has been cloned, expressed and purified to homogeneity. The recombinant MtIMPDH has a subunit molecular weight of 54,775 Da and Inductively-Coupled Plasma Optical Emission Spectroscopy (ICP-OES) and Flame Atomic Absorption Spectroscopy (FAAS) identified a K+ ion per subunit. Glutaraldehyde cross-linking analysis suggests that MtIMPDH predominates as a tetramer. Steady-state kinetics showed that MtIMPDH optimal activity is dependent on the presence of a monovalent cation, mainly K+. Initial velocity and product inhibition patterns suggested a steady-state ordered Bi Bi kinetic mechanism in which IMP binds first followed by NAD+, and hydride transfer is not the ratelimiting step in the MtIMPDH catalyzed reaction. In addition, NAD+ substrate inhibition implies that product release is ordered, with NADH released first. The pH-rate profile indicated one deprotonated group essential for catalysis and that groups with pK values of 7.5 and 9.0 are important for NAD+ binding. The data presented here are discussed in light of the kinetic and structural information available for IMPDHs investigated to date and should inform us on how to better design inhibitors targeting this enzyme. Additionaly, a vital part of drug development is the identification of gene products that are critical for bacterial growth and survival. In this regard, we have performed site-directed mutagenesis by gene replacement in order to evaluate the importance of the guaB2 gene for mycobacteria growth. Our results suggest that this gene is essential for M. tuberculosis H37Rv in vitro growth, and the confirmation of gene essentiality will point out the guaB2-encoded IMPDH as a potential drug target. Data resulting from enzyme s characterization and gene replacement were the starting point for MtIMPDH inhibitors planning, selection and testing. A compound was identified as promising lead molecule, with Ki values in nanomolar range and it was characterized as noncompetitive and uncompetitive inhibitor towards MtIMPDH substrates NAD+ and IMP, respectively. MtIMPDH characterization and results on primary inhibitors identification are crucial step towards a potential novel drug development for TB treatment. Altogether, these data may be useful for a better understanding about the biology of M. tuberculosis and as a framework on which to base efforts towards the development of efficient therapeutic strategies, aiming TB control. / A tuberculose (TB) permanece entre as principais causas de morte por doen?as infectocontagiosas e estima-se que um ter?o da popula??o mundial esteja infectada pelo Mycobacterium tuberculosis. Apesar de existirem tratamentos dispon?veis h? mais de 50 anos, a TB ? respons?vel por causar altas taxas de mortalidade em todo o mundo. A coinfec??o com o HIV e a emerg?ncia de TB resistente a m?ltiplas drogas representam um desafio ? sa?de p?blica e t?m estimulado a pesquisa por novos e mais efetivos agentes terap?uticos contra a doen?a. Avan?os na identifica??o de novos alvos para drogas contra a TB t?m sido poss?veis gra?as ao sequenciamento do genoma do M. tuberculosis H37Rv e incluem a elucida??o da fun??o de prote?nas envolvidas em rotas bioqu?micas essenciais para o crescimento micobacteriano. A enzima Inosina Monofosfato Desidrogenase (IMPDH, EC 1.1.1.205) ? uma enzima chave na bioss?ntese de nucleot?deos de purina, pois participa de uma etapa limitante na s?ntese de novo de nucleot?deos de guanina, a partir de inosina 5 -monofosfato (IMP). Ela catalisa a oxida??o de IMP a xantosina 5 -monofosfato (XMP), com concomitante convers?o de nicotinamida adenina dinucleot?deo (NAD+) ? sua forma reduzida, NADH. Essa rea??o controla os n?veis de nucleot?deos de guanina e inibidores da IMPDH t?m sido utilizados como agentes imunossupressores, antic?ncer e antivirais. Recentemente, a IMPDH de M. tuberculosis (MtIMPDH) foi descrita como um alvo antimicobacteriano promissor e inibidores desta enzima t?m sido reportados. Neste trabalho, foi realizada a clonagem da regi?o codificante do gene guaB2, a express?o e a purifica??o da prote?na MtIMPDH. A MtIMPDH recombinante apresentou uma massa molecular m?dia de 54.775 Da e a an?lise atrav?s de Espectroscopia de Absor??o At?mica em Chama (FAAS) e Espectroscopia de Emiss?o ?ptica com Plasma Indutivamente Acoplado (ICPOES) identificou um ?on K+ por subunidade. Os experimentos de rea??o cruzada, utilizando glutaralde?do, mostraram que a MtIMPDH pode existir como um tetr?mero em solu??o. Os estudos de cin?tica em estado estacion?rio revelaram que a atividade catal?tica da MtIMPDH ? dependente de c?tions monovalentes, principalmente K+. Os estudos de velocidade inicial e inibi??o pelos produtos sugeriram que a cat?lise procede atrav?s de um mecanismo cin?tico sequencial Bi Bi ordenado, no qual o IMP associa-se primeiramente ? MtIMPDH, seguido pela liga??o do NAD+, e que a transfer?ncia do hidreto n?o ? a etapa limitante da rea??o catalisada pela enzima em estudo. Al?m disso, a inibi??o pelo substrato NAD+ indica que a libera??o dos produtos ? ordenada, onde o NADH ? o primeiro produto a ser liberado. Os estudos de perfil de pH indicaram que a desprotona??o de um grupamento com valor de pK em torno de 8,2 ? essencial para a atividade catal?tica da MtIMPDH e, que amino?cidos cujas cadeias laterais possuem valores de pK pr?ximos de 7,5 e 9,0 est?o envolvidos na liga??o ao NAD+. Os dados aqui apresentados s?o discutidos com base em estudos cin?ticos e estruturais dispon?veis de IMPDHs de diferentes organismos e podem auxiliar no desenvolvimento de compostos inibidores para a enzima em estudo. Al?m disso, a identifica??o de genes essenciais para o crescimento bacteriano representa uma etapa importante no desenvolvimento de drogas. Assim, foi realizada a mutag?nese s?tio-dirigida por substitui??o g?nica, a fim de avaliar a import?ncia do gene guaB2 no crescimento do M. tuberculosis H37Rv. Nossos resultados sugerem que este gene ? essencial para o crescimento in vitro do M. tuberculosis H37Rv e a confirma??o da essencialidade permitir? a valida??o do produto deste gene como um alvo para inibidores. Os dados obtidos a partir da caracteriza??o cin?tica da enzima e da substitui??o g?nica representaram o ponto de partida para o planejamento, sele??o e testes de poss?veis inibidores da MtIMPDH. Entre os compostos qu?micos sintetizados, um deles apresentou valores de Ki na faixa de nanomolar e apresentou perfis de inibi??o n?o-competitivo e incompetitivo em rela??o aos substratos NAD+ e IMP, respectivamente. A caracteriza??o da MtIMPDH e os resultados preliminares de inibi??o desta enzima representam passos cruciais no desenvolvimento de novas drogas para o tratamento da TB. Assim, estes dados podem ser ?teis para um melhor entendimento sobre o metabolismo do M. tuberculosis e podem servir como base para o desenvolvimento de estrat?gias terap?uticas objetivando o controle da TB.

Made available in DSpace on 2015-04-14T13:35:49Z (GMT). No. of bitstreams: 1 452038.pdf: 5926182 bytes, checksum: 5375eb92e47f0a2a30ef9fa65dc549c5 (MD5) Previous issue date: 2013-08-08 / Objective: To evaluate the effect of platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) on cutaneous wound healing in rats by comparing treated and control wounds. Material and Methods: Forty-eight Wistar rats were used in the study. Two wounds with 1-cm diameter, of total skin thickness, were excised from the back of the animals and treated with either PRP or PRF and saline (paired model). The wounds were evaluated immediately after the procedure and after 7 and 14 days using macroscopic (photographs) and microscopic (histology) methods. The photographs were used to measure the area of wounds in order to analyse wound contraction (morphometric analysis). The histological images permitted a count-analysis of collagen concentration (histomorphometric analysis) while the histological slides providet the description of the wounds characteristics. Results: Morphometric analysis revealed statistically significant time effect (P<0.001) and treatment group effect (P=0.022) over the observation period. The rate of wound contraction was higher in PRF-treated wounds than in PRP-treated wounds (P=0.030). In the histomorphometric analysis, mean collagen concentration, on the images of the experimental groups, increased significantly (P<0.001) from day 7 to day 14. There was wide variation in the percentage of collagen concentration: 129% in the PRF group vs. 22% in the PRP group; however, this difference did not achieve statistical significance (P=0.380). Histology of the wounds suggested a more accelerated healing process in the PRF group vs. the PRP group, despite the lack of statistical significance in the characteristics analyzed. PRP-treated and PRF-treated groups were not statistically superior to their controls in any of the studied variables. Conclusion: The present results suggest that treatment with PRP and PRF were not more effective than saline for cutaneous wound healing in rats. However, PRF proved to be superior to PRP. / Objetivo: Avaliar o efeito do Plasma Rico em Plaquetas (PRP) e da Fibrina Rica em Plaquetas (PRF) na cicatriza??o de feridas cut?neas em ratos, comparando os tratamentos entre si e com seus respectivos grupos controle. Material e M?todos: Foram utilizados 48 ratos Wistar. Duas feridas de 1,0 cm de di?metro, de espessura total da pele, foram excisadas do dorso dos animais e tratadas com PRP ou PRF e soro fisiol?gico (modelo emparelhado). As feridas foram avaliadas no p?s-operat?rio imediato e depois de 7 e 14 dias, de forma macrosc?pica (fotografias) e microsc?pica (histologia). As fotografias forneceram medidas da ?rea das feridas, possibilitando analisar sua contra??o (an?lise morfom?trica). As imagens histol?gicas permitiram calcular a concentra??o de col?geno nas feridas (an?lise histomorfom?trica) e as l?minas histol?gicas a descrever suas caracter?sticas. Resultados: Quanto ? an?lise morfom?trica, o efeito do tempo (P<0,001) e dos grupos (P=0,022), ao longo do per?odo de observa??o, foi estatisticamente significativo. A taxa de contra??o das feridas tratadas com PRF foi maior do que as tratadas com PRP (P=0,030). Na an?lise histomorfom?trica, a m?dia da concentra??o de col?geno, nas imagens dos grupos experimentais, apresentou um aumento do 7? para o 14? dia, considerado significativo (P<0,001). Houve grande varia??o percentual na concentra??o de col?geno: 129% para a PRF contra 22% para o PRP, por?m, sem signific?ncia estat?stica (P=0,380). A descri??o histol?gica das feridas sugeriu que o grupo PRF apresentou maior acelera??o do reparo quando comparado ao grupo PRP, apesar da aus?ncia de signific?ncia estat?stica nas caracter?sticas avaliadas. Os grupos de tratamento PRP e PRF n?o foram estatisticamente superiores aos seus grupos controle nas vari?veis estudadas. Conclus?o: Os dados do presente estudo sugerem que o PRP e a PRF n?o apresentaram resultados mais eficazes do que o soro fisiol?gico na cicatriza??o de feridas cut?neas em ratos. No entanto, a PRF mostrou-se superior ao PRP.