Introdução: A torção testicular permanece como uma emergência urológica, despertando grande interesse em fármacos que podem minorar a lesão testicular e suas repercussões na fertilidade e produção hormonal. No entanto, não há fármaco aprovado para uso clínico rotineiro. Uma droga estudada em isquemia celular é a clorpromazina, sendo conhecidos seus efeitos protetores na função e estrutura da membrana celular e mitocondrial. Objetivos: Avaliar a diferença na lesão de células germinativas após 1 e 6 horas de torção e a ação da clorpromazina administrada previamente à resolução da torção no testículo isquêmico. Materiais e Métodos: 54 ratos Wistar, machos, com peso corporal entre 220 e 260 gramas distribuídos em 5 grupos: sham, controle com isquemia de 1 hora(A), controle com isquemia de 6 horas(B), experimental com isquemia de 1 hora(C) e experimental com isquemia de 6 horas(D). Em 48 animais foi realizada torção unilateral do cordão espermático com duas voltas em torno do seu eixo (720 graus), fixando-se o testículo nessa posição, após o que cada subgrupo foi separado em avaliação imediata (orquiectomia bilateral ao final do período de torção = 1) e tardia (orquiectomia bilateral, uma semana após a resolução da torção = 2). O grupo experimental recebeu 3 mg/kg de clorpromazina administrada via endovenosa, 30 minutos antes da resolução da torção. O grupo controle recebeu apenas solução salina a 0,9% por via endovenosa. Outros 6 animais formaram o grupo sham, onde foi realizada apenas a manipulação do cordão espermático. Após retiradas as gônadas, foram preparadas para análise histológica pela microscopia de luz e imunohistoquímica.Um pequeno fragmento de cada testículo foi separado para avaliação por microscopia eletrônica de transmissão (MET). Resultados: Na análise por microscopia de luz foram notadas alterações devido à isquemia como, necrose de coagulação e edema intersticial, principalmente nos grupos com isquemia mais prolongada (6h - B e D). Na avaliação por imunohistoquímica, houve maior expressão da caspase-3 nas células e túbulos dos testículos com 6 horas de isquemia, quando comparados com o grupo sham. No entanto, a expressão de bcl-2 não foi expressiva em nenhum grupo. Os grupos B e D também demonstraram alterações mais expressivas na análise por MET. Em nenhuma das avaliações foi observado superioridade do grupo da clorpromazina em relação ao grupo controle. Conclusão: As lesões celulares intratubulares induzidas pela isquemia e reperfusão testicular foram semelhantes após 1 e 6 horas, as diferenças foram relacionadas à sua maior intensidade no grupo com 6 horas e a clorpromazina não foi efetiva na prevenção da lesão por reperfusão. / Introdution: Testicular torsion remains as a urology emergency arousing interest about medicine which can reduce testicular injury and its impact on fertility and hormone production. However, there is no drug approved for routine clinical use. A drug studied in cell ischemia is chlorpromazine, being known its protective effects on the function and structure of cellular membrane and mitochondrial. Objective: To evaluate the difference in lesion of germ cells after 1 and 6 hours and the action of chlorpromazine administered before the resolution of ischemic testicle due torsion. Materials and methods: 54 male Wistar rats weighing between 220 to 260 grams divided into five groups: sham, control with one hour of ischemia (A) control with six hours of ischemia (B) experimental with one hour of ischemia (C) and experimental six hours of ischemia (D). In 48 animals was performed unilateral torsion of the spermatic cord with two laps around its axis (720 degrees), keeping the testicle in this position. After that, each subgroup was divided into immediate evaluation (bilateral orchiectomy at end of the torsion period = 1) or later (bilateral orchiectomy after one week of torsion resolution = 2). The experimental group received 3 mg / kg chlorpromazine administered intravenously 30 minutes before the resolution of torsion. The control group received only saline 0.9% intravenously. Other 6 animals were in the sham group, which was held just handling the spermatic cord. After withdrawal, the gonads were prepared for histological analysis by light microscopy and immunohistochemistry. A small piece of each testis was separated for evaluation by electron microscopy. Results: In analysis by light microscopy, ischemic changes were rated as coagulative necrosis and interstitial edema mainly in groups with prolonged ischemia (6h - B and D). When analyzed by immunohistochemistry, there was greater expression of caspase-3 in cells and tubules of the testes with 6 hour of ischemia compared to the sham group. However, bcl-2 expression was not impressive in either group. B and D groups also showed more significant changes in the analysis by electron microscopy. None of the ratings has been shown superiority of chlorpromazine group over the control group. Conclusion: The germ cell damage induced by ischemia and reperfusion was similar after 1 and 6 hours, the differences were related to its greatest intensity in the group with 6 hours and chlorpromazine was not effective in preventing reperfusion injury.

A isquemia cerebral causada pela parada cardíaca leva ao desapareciemnto neuronal. studamos os mecanismos de morte celular envolvidos na isquemia in vitro em linhagem de neuroblastoma.O insulto isquêmicao foi reproduzido cultivando as células sem fatores de crescimento, sem glicose e em embiente hipóxico produzido por um sistema de anaerobiose. Os resultados sugerem que a privação de oxigênio, glicose e fatores de cresciemtno do meio de cultura reproduzem o fenômeno semelhante a isquemia. INvestigamos ainda a participação de processo apoptótico e sua modulação térmica. Observams que a hipotermia produz neuroproteção, enquanto a hipertermia agrava o processo de morte celular por apoptose. / Cardiac arrest causes cerebral ischemia and neuronal disappearance. We investigate celular death mechanisms elucidated by a model of ischemia in neuroblastoma cell line. The ischemic insult was reproduced by deprivation of growth factors and glucose in a hypoxic environment produced by an anaerobiosis system. Our results validate the experimental model and revel the participation of an apoptotic process in the celular loss induced by ischemia. We also demonstrated that hypothermia can be used as a neuroprotector agent whereas hyperthermia aggavates celular damage.

A isquemia e reperfusão (IR) é a principal causa de insuficiência renal aguda. Evidências mostram a participação de linfócitos T e células dendríticas (DC) na lesão por IR. Entretanto, os mecanismos envolvidos não estão claros. A enzima heme oxigenase (HO)-1 está relacionada à diminuição de respostas inflamatórias. Neste trabalho, investigamos a participação de linfócitos T CD4+ e DC na proteção da lesão por IR induzida pela HO-1. Injetamos em camundongos um indutor de HO-1 (Hemin), e realizamos a IR. Avaliamos a lesão pela uréia e creatinina no soro, a expressão de citocinas por RT-PCR, nível de proteínas por bioplex e perfil celular por FACS. Observamos que a HO-1 protegeu da lesão por IR. A diminuição de INFg com a HO-1 sugeriu uma menor ativação de linfócitos T. No entanto, a transferência de células CD4+ tratadas com Hemin não apresentou diferença. Vimos que a HO-1 alterou o fenótipo das DC após IR e suprimiu a produção de TNFa pelas mesmas. Concluímos que a proteção pela HO-1 é capaz de modular a resposta inflamatória de DC, diminuindo o TNFa. / The ischemia and reperfusion (IR) is the main acute kidney injury. Evidences have shown the role of CD4+ T cells and dendritic cells (DC) in the IR injury. However, the mechanisms involved in the participation of these cells are not clear. The heme oxygenase (HO)-1 enzyme is associated to decrease in inflammatory responses. In this work, we investigated the role of CD4+ T cells and DC in renal injury protection induced by HO-1. We injected in mice a HO-1 inducer (Hemin), and we did the IR. Renal injury was evaluated by serum levels of urea and creatinine, cytokines expression by RT-PCR, proteins level by bioplex and cell profile by FACS. We observed that HO-1 lead to IR injury protection. The IFNg decrease with HO-1 suggested less T cells activation. However, transfer of hemin treated CD4+ cells did not differ from the other group. We observed that HO-1 altered DC phenotype after IR and suppressed TNFa production by these cells. We concluded that the protection by HO-1is able to modulate DC inflammatory response, diminishing TNFa.

Gao Shan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (leaves 191-194). / Abstracts in English and Chinese. / Abstract in English --- p.i / Abstract in Chinese --- p.iii / Acknowledgement --- p.v / Introduction --- p.vi / Contents --- p.viii / List of tables --- p.xiv / List of figures --- p.xv / Chapter Chapter One --- Literature Review / Chapter 1.1 --- Middle Cerebral Artery (MCA) Stenos --- p.is / Chapter 1.1.1 --- Prevalence of atherosclerotic MCA stenosis --- p.2 / Chapter 1.1.2 --- Methods for diagnosis of MCA stenosis --- p.3 / Chapter 1.1.3 --- Possible mechanism and course of stroke with MCA stenosis --- p.4 / Chapter 1.1.4 --- Treatment and prevention of stroke in patients with MCA stenosis --- p.5 / Chapter 1.2 --- Microembolic Signal (MES) Detection / Chapter 1.2.1 --- Introduction --- p.9 / Chapter 1.2.2 --- Technology --- p.9 / Characteristics of MES / Factors that affect MES detection / Problems of technology / Chapter 1.2.3 --- Clinical application --- p.15 / MES originating from atherosclerotic carotid artery stenosis / MES detection in internal carotid endarterectomy (CEA) / MES detection in patients with MCA stenosis / Predicting value and application in therapeutic trial / References --- p.19 / Chapter Chapter Two --- General Methodology / Chapter 2.1 --- Transcranial Doppler (TCD) Diagnosis for Intracranial Artery Stenosis / Chapter 2.1.1 --- TCD spectrum and common parameters --- p.29 / Chapter 2.1.2 --- Emitting and receiving transducers --- p.29 / Chapter 2.1.3 --- Pulsitility index (PI) --- p.31 / Chapter 2.1.4 --- Insonation depth and flow direction --- p.31 / Chapter 2.1.5 --- Continuous wave (CW) and pulsed wave (PW) --- p.33 / Chapter 2.1.6 --- Normal intracranial arteries through temporal and suboccipital window --- p.33 / Chapter 2.1.7 --- Normal intracranial arteries through orbital window --- p.36 / Chapter 2.1.8 --- Normal extracranial arteries --- p.36 / Chapter 2.1.9 --- TCD diagnosis for intracranial artery stenosis --- p.39 / Chapter 2.1.10 --- Example of multiple intracranial arteries stenosis --- p.39 / Chapter 2.2 --- Microembolic Signal (MES) Detection / Chapter 2.2.1 --- Device of MES monitoring --- p.41 / Chapter 2.2.2 --- Insonated artery and depth --- p.41 / Chapter 2.2.3 --- Axis length of the sample volume --- p.43 / Chapter 2.2.4 --- Fast Fourier Transform (FFT) time window overlap --- p.43 / Chapter 2.2.5 --- Distinguishing embolic signal and artifact with two-gate transducer --- p.45 / Chapter 2.2.6 --- Measurements of embolic signal and threshold --- p.47 / References --- p.45 / Chapter Chapter Three --- Prevalence and Clinical Significance of Microembolic Signal (MES) in Patients with Middle Cerebral Artery (MCA) Stenosis / Chapter 3.1 --- Abstract --- p.50 / Chapter 3.2 --- Introduction --- p.51 / Chapter 3.3 --- Methodology --- p.51 / Patients / Severity of stroke and clinical course / Diagnosis for middle cerebral artery (MCA) stenosis / Microembolic signal (MES) detection / Statistical analysis / Chapter 3.4 --- Results --- p.55 / Baseline information of patients / Prevalence of MES / Relationship between presence of MES and severity of MCA stenosis / Correlation between presence of MES and clinical course in 85 symptomatic patients / Correlation between the count of MES and clinical course in 85 symptomatic patients / Correlation between the presence of MES and further ischemic stroke / Chapter 3.5 --- Discussion --- p.63 / Prevalence of MES / Association between severity of stroke and presence or the number of MES / Predictive value of MES for further stroke / References --- p.66 / Chapter Chapter Four --- Mechanisms of Acute Cerebral Infarction in Patients with Cerebral Artery Stenosis: a Diffusion-weighted Imaging and Microemboli Monitoring study / Chapter 4.1 --- Abstract / Chapter 4.2 --- Introduction --- p.72 / Chapter 4.3 --- Methodology --- p.73 / Patients / Microembolic signal (MES) detection by transcranial Doppler (TCD) / "Magnetic resonance imaging (DWI, MRI and MRA)" / Statistical analysis / Chapter 4.4 --- Results --- p.77 / Severity of MCA stenosis on MRA and pattern of infarct on DWI / Frequency and count of MES and its relationship with multiple and borderzone infarction on DWI / Chapter 4.5 --- Discussion --- p.79 / Frequency of MES / Pattern of cerebral infarcts on DWI / Relationship between MES and multiple infarcts on DWI / References --- p.83 / Chapter Chapter Five / Chapter Chapter Five-I --- Novel Observations of the Characteristics of Real Time Genesis of Thromboembolism in Middle Cerebral Artery Stenosis Detected by Transcranial Doppler / Chapter 5.1.1 --- Abstract --- p.90 / Chapter 5.1.2 --- Introduction --- p.91 / Chapter 5.1.3 --- Methodology --- p.91 / Characteristics of patients / "MRA, DWI and conventional TCD data" / MES monitoring method and overall data / Neuroimaging and MES monitoring data in all five patients / Signal analysis in off-line / Confirmation test for the origin of MES / Chapter 5.1.4 --- Results --- p.104 / Frequency of three special phenomena / Characteristics of three special phenomena / Results of confirmation test for embolic source / Chapter 5.1.5 --- Discussion --- p.133 / Occurrence of MES with flow velocity change simultaneously / MES splatter / Bi-directional low frequency (S-velocity) vibration / Testing for source of MES detected from MCA stenosis / References --- p.139 / Chapter Chapter Five-II --- Characteristics of Microembolic Signals Detected near Its Origin from the Middle Cerebral Artery Stenosis / Chapter 5.2.1 --- Abstract --- p.143 / Chapter 5.2.2 --- Introduction --- p.144 / Chapter 5.2.3 --- Methodology --- p.144 / Patients / Microembolic signal (MES) detection / Classification of MES / Chapter 5.2.4 --- Results --- p.145 / Types of MES detected from MCA stenosis / Characteristics of three types of MES / Chapter 5.2.5 --- Discussion --- p.157 / Emboli moving from vessel wall to the center / Emboli vibration / About calculating the time delay between two channels / References --- p.160 / Chapter Chapter Five-III --- "Hemodynamic change,microembolic signal counts and use of antithrombotic treatments" / Chapter 5.3.1 --- Abstract --- p.163 / Chapter 5.3.2 --- Introduction --- p.164 / Chapter 5.3.3 --- Methodology --- p.164 / Chapter 5.3.4 --- Results / "The relationship among flow velocity, the number of MES and time since symptom onset" --- p.165 / Patient one / Patient two / Patient three / Chapter 5.3.5 --- Discussion / Association between flow velocity or MES change and different anticoagulants in acute stage / Progression of MCA stenosis after acute stage / Stability of MCA atherosclerotic stenosis / References --- p.173 / Chapter Chapter Six --- The Optimal Values of Flow Velocity on Transcranial Dopplerin Grading Severity of Middle Cerebral Artery Stenosis in Comparison With Magnetic Resonance Angiography / Chapter 6.1 --- Abstract --- p.179 / Chapter 6.2 --- Introduction --- p.180 / Chapter 6.3 --- Methodology --- p.180 / Patients / TCD examination / Grading of MCA stenosis on MRA / Statistical analysis / Chapter 6.4 --- Results --- p.182 / Detection of >50% MCA stenosis according to flow velocity / Grading severity of MCA stenosis by flow velocity / Chapter 6.5 --- Discussion --- p.186 / Reliability of TCD diagnosis for MCA stenosis / Grading MCA stenosis according to flow velocity on TCD / References / Abbreviations --- p.189 / Publications --- p.191

Submitted by Eunice Novais (enovais@uepg.br) on 2018-08-17T19:14:59Z No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Rafael Inacio Brandão.pdf: 6353891 bytes, checksum: 8e384db8b4012f1f363df49c4c1b65b2 (MD5) / Made available in DSpace on 2018-08-17T19:14:59Z (GMT). No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Rafael Inacio Brandão.pdf: 6353891 bytes, checksum: 8e384db8b4012f1f363df49c4c1b65b2 (MD5) Previous issue date: 2016-03-14 / A isquemia é um dos problemas mais frequentes e desafiadores com que os cirurgiões vasculares se defrontam e é ao mesmo tempo paradoxal, pois, ao restabelecer o fluxo sanguíneo para um tecido podem ser desencadeadas alterações locais ou sistêmicas mais intensas que a isquemia per se. Estas complicações estão relacionadas com a liberação de radicais livres de oxigênio. O objetivo deste estudo foi avaliar os efeitos do antioxidante alopurinol e do pós condicionamento isquêmico (PCi), que são ciclos de reperfusão intercalados com ciclos de isquemia, sobre as consequências deletérias da isquemia seguida de reperfusão em um modelo de isquemia padronizado em membros caudais de ratos. Este estudo foi aprovado pelo CEUA da Universidade Estadual de Ponta Grossa. Para tanto foram utilizados 30 ratos da linhagem Wistar, fêmeas, com aproximadamente 3 meses de idade. Os animais foram aleatoriamente distribuídos em cinco grupos: Grupo A (SHAM): animais que não foram submetidos a isquemia dos membros caudais; Grupo B : animais submetidos a 2 horas de isquemia e reperfusão apenas uma vez; Grupo C : animais receberam, por gavagem a dose de 100 mg/kg de alopurinol, uma hora antes do procedimento cirúrgico, depois foram submetidos a 2 horas de isquemia e reperfusão apenas uma vez; Grupo D: animais foram submetidos a 2 horas de isquemia e três ciclos de reperfusão (dois minutos cada) intercalados com três ciclos de isquemia (dois minutos cada) e Grupo E : animais receberam dose de 100 mg/kg de alopurinol, uma hora antes do procedimento cirúrgico, depois submetidos a 2 horas de isquemia e três ciclos de reperfusão (dois minutos cada) intercalados com três ciclos de isquemia (dois minutos cada). Três dias após foram coletadas amostras de sangue para análises bioquímicas: Ureia, Creatinina, Aspartato aminotransferase, Alanina aminotransferase, Creatinoquinase, Lactato e mensuração da capacidade antioxidante total pelo método baseado no 2,2”- azinobis 3-etilbenzotiazolina-6-ácido sulfônico (ABTS) e coleta de segmentos do intestino delgado para análises histológicas. Foi observado efeito protetor do uso de alopurinol e do Pós condicionamento isquêmico através da mensuração da creatinina, AST, ALT e lactato, que preveniram o aumento causado pela isquemia. Com relação a Capacidade Antioxidante Total, ficou evidente o benefício do PCi, mas não do alopurinol. Em relação as análises histológicas, ambos os métodos foram eficazes em minimizar os efeitos lesivos do processo de isquemia e reperfusão mesentérica. Logo pode-se concluir que, o alopurinol e mais notadamente o PCi exerceram efeito protetor, alcançando significância estatística. / Ischemia is one of the most common and challenging problems that vascular surgeons are facing and is at the same time paradoxical, therefore, to restore blood flow to a tissue can be triggered local or systemic changes more intense than ischemia per se. These complications are related to release of oxygen free radicals. The aim of this study was to evaluate the effects of allopurinol antioxidant and post ischemic conditioning on the deleterious effects of ischemia followed by reperfusion in a standardized ischemia model in rat members’ flows. This study was approved by CEUA the State University of Ponta Grossa. Therefore, we used 30 Wistar rats, female, approximately 3 months old. The animals were randomly divided into five groups: Group A (SHAM ): Animals that were not subjected to ischemia of the caudal members; Group B: Animals subjected to 2 hours of ischemia and reperfusion only once; Group C: animals were given by gavage at a dose of 100 mg / kg of allopurinol, one hour before surgery, they were then subjected to 2 hours of ischemia and reperfusion only once; Group D: Animals were subjected to 2 hours of ischemia and three reperfusion cycles (two minutes each) interleaved with three ischemia cycles (two minutes each) and Group E: Animals received 100 mg / kg of allopurinol, one hour before the surgical procedure, then subjected to 2 hours of ischemia and reperfusion for three cycles (two minutes each) interleaved with three cycles of ischemia (two minutes each). Three days after Blood samples were collected for biochemical analysis: Urea, Creatinine, Aspartate aminotransferase, Alanine aminotransferase, Creatine kinase, Lactate and measurement of the total antioxidant capacity by the method based on 2.2”- azinobis 3- ethylbenzothiazoline -6- acid sulfonic (ABTS) and collection segments of the small intestine for histological analysis. It was observed protective effect of the use of allopurinol and Post conditioning (PCi) ischemic by measuring creatinine, AST, ALT and lactate, which did not show a significant increase. Regarding the Total Antioxidant Capacity was evident the benefit of PCi, but not of allopurinol. As to the histological analyzes, both methods were effective in minimizing the harmful effects of ischemia and reperfusion process mesenteric. As a result it can be concluded that allopurinol and especially PCI exerted a protective effect, reaching statistical significance.

Este trabalho visa avançar o conhecimento sobre a interferência da nicotina no protocolo de treino forçado em gerbilos isquêmicos. Utilizamos 110 Gerbilos, distribuídos em 11 grupos. Grupo controle com animais ingênuos (C), falso operado (S) e isquêmicos (I). Grupos nicotina (CN, SN, SNE, IN e INE) e salina (CS, SS, IS) com ou sem treinamento. Os animais receberam uma injeção de 2mg/kg de nicotina ou salina durante 9 dias. Utilizamos uma esteira motorizada (treino contínuo, 5 dias, 5m/min por 15 minutos), um monitor de atividades e o Rota Rod. Os resultados foram analisados por uma ANOVA e pós teste de Holm-Sidak, p<0,05. Observamos aumento de apresentação de todos comportamentos no monitor de atividades, o CN maior do que os C, S, SS, SNE e INE, o SN maior do que o SNE, o I maior do que os C, S, SS, SNE, IS, INE e ainda, o IN maior do que os C, S, SS, SNE, IS e INE (cruzamento, F10,93 = 2,97), (distância, F10,93 = 2,79), (velocidade, F10,93 = 2,79) e (atividade, F10,93 = 2,81). No Rota Rod o CN apresentou maior tempo de permanência com relação aos outros grupos exceto SNE, já o SNE, em relação aos CS, S, SN, I, IN e o I menor tempo de permanência do que o C e INE (F10,93 = 3,35). Nos grupos I e IS observamos menor densidade de neurônios no hipocampo (F6,42 = 31,02), córtex motor M1 (F6,42 = 4,01) e estriado (F6,42 = 23,33). A nicotina não interferiu com a melhora do comportamento dos animais isquêmicos. / This work aims to advance the knowledge about the interference of nicotine in the forced training protocol in ischemic gerbils. We use 110 gerbils, distributed in 11 groups. Control (C), false operated (S) and ischemic (I). Nicotine groups (CN, SN, SNE, IN INE) and sham (CS, SS, SI) with or without training. The animals received an injection of 2mg/kg of nicotine or saline for 9 days. We use a treadmill (continuous training 5 days, 5m / min for 15 minutes), an activity monitor and the Rota Rod (RR). The results were analyzed by an ANOVA and post Holm-Sidak test, p <0.05. We observed increased in all behaviors in the activity monitor, increase of CN than C, S, SS and NSS INE, SN increase compared to NES, the I increase than C, S, SS, ENS, S, NSI and also the IN showed an increase compared to C, S, SS, SNE, SI and NSI (crossing, F10,93 = 2,97), (distance, F10,93 = 2,79), (speed, F10,93 = 2,79) and (activity, F10,93 = 2,81). In RR, CN showed an increase of time spent with the other groups except SNE, and an increase in the SNE, compared to the CS, S, SN, I, IN and I showed an decrease of time compared to C and INE (F10,93 = 3,35). In groups I and and IS we observed an decrease of neurons density in the hippocampus (F6,42 = 31,02), motor cortex M1 (F6,42 = 4,01) and striatum (F6,42 = 23,33). Nicotine did not interfere with the improvement of motor behavior in ischemic animals.

Introdução: A isquemia-reperfusão hepática é um fenômeno inerente aos procedimentos cirúrgicos sobre o fígado. Descrita pela primeira vez em 1975, apresenta efeitos maléficos tanto locais quanto sistêmicos que aumentam a morbidade e mortalidade dos pacientes. Dentre as formas de se atenuar o processo, a utilização de drogas anti-inflamatórias como a solução salina hipertônica a 7,5% (SSH) e a pentoxifilina vêm sendo testadas com este propósito. As duas substâncias foram utilizadas conjuntamente (HPTX) em modelos experimentais em choque hemorrágico. Contudo, na isquemia-reperfusão de origem hepática, estas foram administradas apenas isoladamente, o que torna o presente estudo pioneiro nesta avaliação. Objetivo: Avaliar os efeitos da solução salina hipertônica a 7,5% associada a pentoxifilina na isquemia-reperfusão hepática. Métodos: Foram utilizados 138 ratos Wistar divididos em quatro grupos de acordo com o tratamento empregado: GC - grupo controle (sem tratamento), SSF - solução salina fisiológica, SSH - solução salina hipertônica a 7,5% e HPTX solução salina hipertônica a 7,5% associada a pentoxifilina. A isquemia hepática foi realizada seletivamente sobre o pedículo comum do lobo mediano e ântero-lateral esquerdo pelo período de 60 minutos. As soluções foram administradas 15 minutos antes da reperfusão hepática. No sangue, foram analisadas as dosagens de transaminases hepáticas nos períodos de quatro e 12 horas e, interleucina-6 e interleucina-10 no período de 12 horas. No tecido pulmonar foram avaliadas as dosagens de azul de Evans e mieloperoxidase pulmonar nos períodos de quatro e 12 horas e, no tecido hepático do lobo isquêmico e não-isquêmico foram analisadas as dosagens de malondialdeído e a avaliação da respiração mitocondrial no período de quatro horas e a histologia nos períodos de quatro, 12 e 24 horas. Resultados: Os grupos tratados com SSH isolada ou em conjunto com a pentoxifilina apresentaram níveis significantemente menores (p<0,05) nas dosagens de transaminases e interleucina-6 em comparação aos outros dois grupos (GC e SSF). Resultados semelhantes entre os grupos foram observados no tecido pulmonar através da análise do azul de Evans e mieloperoxidase pulmonar em quatro e 12 horas e no tecido hepático com relação à respiração mitocondrial. No grupo no qual se adicionou pentoxifilina, houve diminuição estatisticamente significante da peroxidação lipídica e da permeabilidade pulmonar tardia quando comparado ao grupo SSH. Conclusões: A utilização em conjunto das duas soluções reduziu: a resposta inflamatória sistêmica; as lesões histológicas e funcionais do fígado; o estresse oxidativo e a permeabilidade pulmonar / Introduction: The liver ischemia/reperfusion (I/R) injury caused by prolonged ischemia time triggers frequently a systemic inflammatory syndrome leading to remote organ damage. Previous studies have shown that resuscitation with hypertonic saline and pentoxifylline (HPTX) attenuates hemorrhagic shock-induced injury when compared with Ringers lactate. However, it remains unclear if the HPTX protective effect occurs on liver I/R-induced injury, and if this effect overcomes the benefits of HTS used alone. Objective: Evaluated the effects of the combination of hypertonic saline solution (HTS) and pentoxifylline (PTX) on liver I/R injury in rats. Method: One hundred thirty eigth male Wistar rats underwent to one hour of partial liver ischemia performed by clamping the pedicle from the medium and left lateral lobes. Rats were divided into 4 groups: ischemia control group (C), normal saline (0.9% NaCl, 34ml/Kg) treated group (NS), hypertonic saline (7.5%NaCl, 0.4ml/Kg) treated group (HTS), and 7.5% NaCl (0.4ml/Kg) + PTX (25mg/Kg) treated group (HPTX). Samples were collected 4, 12 and 24 hours after reperfusion for determinations of serum AST, ALT, IL-6, and IL-10 levels, liver histology, liver mitochondrial oxidation and phosphorylation, and lipid peroxidation and pulmonary vascular permeability and myeloperoxidase (MPO). Results: The results showed a significant decrease in AST and ALT serum levels in HTS and HPTX groups compared to C and NS groups. Also a significant decrease in mitochondrial dysfunction was observed in HTS and HPTX groups compared to C and NS groups. The oxidative stress was significant decreased in HPTX group compared to C, NS and HTS groups in both ischemic and non-ischemic liver lobes. Elevation in serum IL-6 was significantly lower in HTS and HPTX groups compared to C and NS groups, but there was no difference in IL-10 levels. Pulmonary vascular permeability was significantly lower in groups HTS and HPTX compared with NS group, and even lower in HPTX group compared to HTS group (P < .05). Conclusion: These data suggest that addition of pentoxifylline to hypertonic saline solution decreases the inflammatory response of the liver ischemia/reperfusion injury, decreasing the liver damage as well the pulmonary injury

Ho Sin Yee, Stella. / "August 2002." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (p. 167-193). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

L’ischémie d’exercice caractérisée par l’incapacité du système circulatoire de faire face à l’augmentation des besoins en substrats énergétiques et en oxygène nécessaire à dégrader ces substrats. La claudication à la marche est une cause majeure de limitation fonctionnelle.Il existe de nombres techniques d'évaluation de la macrocirculation et de la microcirculation permettant d'évaluer la réponse endothéliale dépendante(iontophorèse, test au garrot, modification de température locale) avec un enregistrement laser Doppler ou Speckle.Si les techniques ultrasonores permettent d’explorer la présence de lésions, elles rendent mal compte de la collatéralité. Ces techniques peu applicables à l’exercice et nécessitent d’être améliorées pour être applicables à l’effort. L’ischémie artérielle, entraîne une souffrance cellulaire avec métabolisme anaérobie, réversible à l’arrêt de l’exercice. En cas de développement de circulation collatérale suffisante, l’ischémie est alors incomplète, la souffrance des tissus est modérée et réversible rapidement. La recherche de pathologie artérielle au reposa été largement étudiée, nous nous intéressons dans nos études à la pathologie artérielle à l’effort, mais aussi aux phénomènes physiopathologiques susceptibles d’interférer avec la fonctionnalité musculaire (hypoxémie induite par l’exercice). La mesure de la pression partielle transcutanée en oxygène (TcpO2) à l’exercice permet d’estimer en cours de l’exercice l’importance de l’ischémie, segment de membre par segment de membre,de façon bilatérale et continue. Par cette nouvelle technique nous tentons d’explorer la physiopathologie de l’ischémie vasculaire à l’exercice. / Exercise ischemia is characterized by the inability of the circulatory system to fulfil the increased need forenergy substrates and the oxygen needed for substrates’ metabolism. Claudication is a major cause of functional limitation. There are several methods for assessing macrocirculation (mainly ultrasound imaging) and microcirculation (iontophoresis, tourniquet test, local temperature modification with Laser or Speckle recording. If ultrasound techniques can explore the occurrence of lesions is not optimal to evaluate the hemodynamic consequences because pressure measurements do not necessarily correlate with flow impairment. Laser techniques are not appropriate during exercise tests and need to be improved to be applicable. During exercise the severity of arterial ischemia depends on collateral circulation. Further ischemia is reversible at the end of exercise. Although research of restingarterial ischemia has been extensively studied few isknown in arterial ischemia during exercise, but al soin other physiopathological dysfunctions that may interfere with muscle function (exercise-inducedhypoxemia). The measurement of the transcutaneous oxygen partial pressure (TcpO2) during exercise estimates during exercise the importance of ischemia, limb segment by limbsegment, bilaterally and continuously. With this new technique we try to investigate the Physiopathology of vascular ischemia during exercise.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / O objetivo do presente estudo foi verificar os efeitos da L-alanil-glutamina (Ala-Gln) na isquemia e reperfusÃo em cÃrebro de ratos. Foram utilizados 48 ratos machos, da linhagem Wistar, com idade mÃdia de 62 dias e peso mÃdio de 276,38g, distribuÃdos em quatro grupos: Sham 30 minutos, Isquemia, Sham 90 minutos e Isquemia/ ReperfusÃo. Foi utilizado um modelo de isquemia cerebral experimental global, com oclusÃo da artÃria carÃtida comum bilateral e administraÃÃo de soluÃÃo salina ou Ala-Gln. Os resultados do presente estudo mostraram elevaÃÃo estatisticamente significante no percentual de Ãrea de necrose do grupo Isquemia (13,24  8,82) em relaÃÃo ao grupo Sham 30 minutos (0,12  0,20, p= 0,01). O mesmo ocorreu em relaÃÃo à Ãrea de necrose do grupo Isquemia/ReperfusÃo (13,30  9,91) em relaÃÃo ao Sham 90 minutos (0,70  1,35, p= 0,01). Tais resultados demonstram a efetividade do modelo Isquemia e Isquemia/ReperfusÃo cerebrais utilizados. NÃo foi observada alteraÃÃo significante no percentual de Ãrea de necrose entre os grupos Isquemia Salina (13,24  8,82) e Isquemia Ala-Gln (15,35  6,80, p= 0,34). A mÃdia do percentual de Ãrea isquÃmica do grupo Isquemia/ReperfusÃo Ala-Gln (4,65  1,44) foi significantemente inferior Ãquela encontrada no grupo Isquemia/ReperfusÃo Salina (13,30  9,91, p= 0,03). A administraÃÃo prÃvia de Ala-Gln a ratos submetidos à Isquemia/reperfusÃo cerebral nÃo promoveu reduÃÃo no percentual de Ãrea de necrose na lesÃo isquÃmica. Por outro lado, esse dipeptÃdeo reduziu o percentual de necrose cerebral na lesÃo Isquemia/ReperfusÃo cerebral. / The aim of this study was to investigate the effects of L-alanyl-glutamine (Ala-Gln) in ischemia and reperfusion in rat brain. We used 48 male rats, Wistar, with a mean age of 62 days and average weight of 276.38 g, divided into four groups: Sham 30 minutes ischemia, 90 minutes and Sham Ischemia / Reperfusion. We used a model of experimental global cerebral ischemia with occlusion of bilateral common carotid artery and administration of saline or Ala-Gln. The results of this study showed a statistically significant increase in the percentage of necrotic area of the ischemia group (13.24  8.82) than in group Sham 30 minutes (0.12  0.20, p= 0.01). The same occurred in relation to the area of necrosis in ischemia-reperfusion group (13.30  9.91) compared to Sham 90 minutes (0.70  1.35, p= 0.01). These results demonstrate the effectiveness of the model Ischemia and Ischemia / Reperfusion brain used. There was no significant change in the percentage of necrotic area between Salina ischemia groups (13.24  8.82) and ischemia Ala-Gln (15.35  6.80, p= 0.34). The average percentage of ischemic area of group Ischemia / Reperfusion Ala-Gln (4.65  1.44) was significantly lower than that in group Ischemia / Reperfusion Salina (13.30  9.91, p= 0.03). The prior administration of Ala-Gln in rats subjected to ischemia / reperfusion did not cause reduction in the percentage of necrosis in ischemic injury. Moreover, this dipeptide reduced the percentage of necrosis in the cerebral injury cerebral ischemia / reperfusion.