A revascularização cardíaca utilizando a ponte de safena é um procedimento bastante comum usado para restabelecer o fluxo coronariano. O sucesso do implante depende da adaptação do vaso que estava em um regime hemodinâmico venoso, e passa subitamente para um regime arterial. Durante este processo adaptativo, ocorrem diversas alterações moleculares cujo conhecimento pode fornecer alternativas de melhoramento da patência dos enxertos venosos em leito arterial. Neste trabalho está sendo investigada a regulação da IL-1beta tanto em veia safena humana como em modelo animal de arterialização venosa. A IL-1beta mostrou-se aumentada em veia safena humana arterializada tanto in vivo como ex vivo. Interessantemente, este aumento observado nos dias iniciais (1-5 dias) parece diminuir em tempos mais tardios (1-4 anos). Em modelo de arterialização de rato foi observado aumento de 12 vezes na expressão da IL-1beta após o primeiro dia de arterialização com diminuição posterior, mantendo-se em torno de 2 vezes maior em comparação a veia jugular normal. Além da regulação temporal da IL-1beta, foram também acompanhadas as alterações morfológicas que ocorrem durante o processo de arterialização venosa. Observou-se uma redução gradual de células musculares lisas (SMC) que quase desaparecem 3 dias após a cirurgia. Esta perda celular pode estar relacionada ao pico de apoptose observado já no primeiro dia de arterialização. Após 7 dias as SMC reaparecem, porém, de maneira ainda desorganizada. Concomitante com o reaparecimento das SMC observou-se progressivo espessamento da camada média, assim como surgimento de uma camada neoíntima. A IL-1beta, devido ao seu padrão de regulação assim como sua localização durante o processo de arterialização, pode estar relacionada com as alterações estruturais verificadas na arterialização do enxerto. Estratégias de intervenção modulando a atividade da IL-1beta poderão fornecer indicativos da sua participação no remodelamento do enxerto venoso. Em conjunto, demonstramos que o modelo de arterialização de segmento venoso em rato reproduz várias das alterações morfológicas descritas na doença do enxerto venoso em humanos e por isso será útil na caracterização de genes candidatos que participam deste processo. A IL-1beta tem sua expressão aumentada em segmento venoso arterializado in vivo e ex vivo, podendo representar um interessante alvo para aplicação de metodologias de intervenção visando influenciar a adaptação de enxertos venosos com finalidade terapêutica / The vein graft is subjected to increased tensile stress and the complex adaptive vein response to the arterial hemodynamic condition may predispose to bypass failure in some individuals. The understanding of molecular changes underlying this process may be useful for the development of novel therapeutical interventions to increase the vein graft patency. In this work, we investigated the early effect of arterialization on the expression of IL-1beta gene in human saphenous vein and the time-course regulation in rat arterialization model. IL-1beta is upregulated in early stage of human saphenous vein arterialization in vivo and ex vivo. This increase is also observed in arterialized rat jugular vein which showed IL-1beta expression 12 times higher on day 1 compared to normal jugular vein. Later, the IL-1beta levels decreases and maintain the level about twice above normal jugular vein. Moreover, it is observed gradual reduction of smooth muscle cells (SMC), which almost disappeared on the 3rd day after surgery. Apoptosis, which is markedly increased on the 1st day, appears to be an important event during this process. At the 7th day, cellular density and SMC proliferation gradually increased till the 90th day. There was a gradual thickening of the medial layer and formation of neointima with deposition of SMC in the subendotelial layer from day 7 on. Initially the medial layer appeared disorganized, day 7 to 14, then by day 28 it became more organized and the presence of an intimal layer with SMCs was evident. The neointimal layer increased gradually from day 7 on. These results provide evidence that the modulation of IL-1beta activity may be an interesting target to be explored I the future to increase the vein graft patency. Altogether, we demonstrate that the model of arterialization of venous segment in rat reproduces several of the morphological changes described in the venous graft disease in humans and thus will be useful in characterization of candidate genes involved in this process and testing them as a potential therapeutic targets. The IL-1beta expression is increased after 1 day of arterialization of vein segment in vivo and ex vivo and shall be an interesting target to be tested to influence the adaptation of venous grafts for therapeutic purpose

Avaliou-se a prevalência de hipertensão arterial sistêmica (HAS) e a variação circadiana da pressão arterial (PA), através da Monitorização ambulatorial da pressão arterial (MAPA), em pacientes com oclusão do ramo da veia central da retina (ORVCR). Foram avaliados, prospectivamente, 93 casos/olhos de 83 pacientes. A ausência do descenso fisiológico da PA durante o sono ("non-dipper") foi definida como diminuição da pressão sistólica = 10% e a presença de descenso quando este valor fosse maior ("dipper"). Há uma prevalência extremamente alta (94%) de HAS em pacientes com ORVCR. Entre os hipertensos, uma grande parcela dos indivíduos "non-dipper" (n=34; 44,2%). Estas evidências sugerem que um nível mais sustentado de PA nas 24 horas possa ser um fator de risco para o desenvolvimento da ORVCR / Objective: Identifying with Blood pressure monitoring (BPM) in patients with branch retinal vein occlusion (BRVO): high blood pressure (HBP) prevalence, possible cases of white-coat normotension (WCNT) and variation of circadian blood pressure (BP). Methods: Prospectively, 93 cases/eyes of 83 patients with BRVO were evaluated at Ophthalmological Clinic of "Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo" (HCFMUSP). After that, patients were taken to Hypertension League of Nephrology Chair of HCFMUSP (LH-HCFMUSP) for clinical evaluation and blood pressure monitoring. Non-dipper was defined as a fall in systolic blood pressure = 10%, and dipper when this value was higher

Die vorliegende Arbeit behandelt die Prinzipien und Grundlagen der koronaren Bypassoperation. Die Resultate wie Operationsrisiko, Überlebens- und Krankheitsraten sowie die Durchgängigkeitsraten der verschiedenen Grafttypen werden basierend auf dem aktuellen Stand der Literatur erläutert. Die Ätiologie und Pathogenese der Atheromatose sowie die Venengraftsklerose werden diskutiert. Bei der Sklerose der Venengrafts handelt es sich primär im Wesentlichen um einen Adaptationsprozess des Gefäßes an die arteriellen Blutdrücke (Wandstress) und Strömungsverhältnisse (Scherkraft), der sekundär durch die grundsätzlichen Mechanismen der Atheromatoseentwicklung überlagert wird. Schließlich wird das Biocompound-Verfahren vorgestellt, welches durch die Umhüllung der Graftvene mit einem hoch flexiblen Flechtschlauch aus einer Stahllegierung den Wandstress herabsetzt sowie in Folge des verringerten Graftdurchmesseres zu einem günstigen Ausmaß der Scherkraft führt und so die Graftsklerose reduziert. Abschließend folgt eine Übersicht der aktuellen Literatur über die verschiedenen medikamentösen Therapien zur Verzögerung der Graftsklerose. / This review treats the principles and fundamentals of the coronary bypass operation. The results in terms of the risk involved in the operation, survival and morbidity rates and the patency rates of the different types of graft are dealt with on the basis of the current literature. The etiology and pathogenesis of atheromatosis and vein graft sclerosis are discussed. Sclerosis of the vein graft is primarily a process by which the vessel adapts to the arterial blood pressure (wall stress) and flow factors (shear stress); it is, secondarily, overlaid by the basic mechanisms at work in the development of atheromatosis. Finally, the biocompound procedure is introduced. This method reduces the wall stress by sheathing the grafted vein with a highly flexible mesh tubing of steel alloy, leading to more favorable shear force conditions by reducing the diameter of the graft and thereby reducing graft sclerosis. The study closes with an overview of the current literature on the different drug therapies used to delay graft sclerosis.

Hypercoagulable states occur when the process of hemostasis is disturbed. It manifests as a deep vein thrombosis or a pulmonary embolism. It is also one of the most common cardiovascular diseases. There are two factors- genetic and acquired. Inherent factors involve coagulation inhibitor deficiency, prothrombin gene mutation and activated protein C resistance. Acquired factors include antiphospolipid syndrome, pregnancy, overweight etc. The analytic part of the thesis is focused on the effect of a low molecular weight heparin. It was shown in many theses that the LMWH could have a negative impact on a parturition complications or a week of parturition, a birth weight. The results of statistical analysis show that there is a coherence between the week of parturition and the type of parturition. What is more, the anticoagulation drug therapy shows a positive effect on the week of parturion. The data used in the thesis originate in laboratory information management system of Clinical Haematology ward in the hospital Nemocnice České Budějovice a.s.

Introdução: as alças vasculares podem prover o suprimento sanguíneo adequado para um retalho microcirúrgico em um leito desfavorável, como fratura exposta ou área irradiada após a ressecção de tumores. Apesar de realizadas na prática clínica, há falta de estudos demonstrando quais os fatores são responsáveis pelo seu sucesso. Objetivo: avaliar, em coelhos, qual é a influência do desenho da alça de veia femoral com anastomose na artéria femoral, na presença de fluxo (patência) após sete dias. Método: Trinta e nove coelhos foram submetidas à microanastomose arteriovenosa com técnica microcirúrgica. As alças foram acomodadas em dois desenhos, um, chamado \"circular\" e outro, o mais alongado possível sem dobras na alça. Os parâmetros avaliados foram: presença ou não de fluxo, sinais de hemólise, alterações hemodinâmicas sofridas pela veia submetida à pressão arterial. Resultados: Após sete dias, o fluxo estava presente em 68% das alças \"anguladas\" e em 75% das alças \"circulares\" (p > 0,05). Houve, intragrupo, diminuição estatisticamente significante da pCO2 e aumento estatisticamente significante do pH. Não houve diferença estatisticamente significante no restante dos parâmetros avaliados entre os dois modelos de alça. Conclusão: O desenho da alça vascular arteriovenosa na pata do coelho não interfere na sua patência em um período de sete dias / Introduction: the vascular loops can provide adequate blood supply to a microsurgical flap in an unfavorable bed as open fracture or irradiated area after resection of tumors. Although performed in clinical practice, there is a lack of studies showing which factors are responsible for their success. Objective: To evaluate, in rabbits, which is the influence in the presence of flow (patency) of femoral vein loop design in anastomosis of the femoral artery after seven days. Method: Thirty-nine rabbits were subjected to arteriovenous microanastomosis with microsurgical technique. The loops were accommodated in two designs, one named \"circular\" and the other, the more elongated possible without folds. The parameters evaluated were: presence or absence of flow, hemolysis, hemodynamic changes suffered by vein submitted to blood pressure. Results: After seven days, the flow was present in 68% of angled loops and 75% of the \"circular\" loops (p > 0.05). There was intra-group, statistically significant decrease in the pCO2 and statistically significant increase in pH. There was no statistically significant difference in the rest of the parameters evaluated between the two loop models. Conclusion: The design of arteriovenous vascular loops in the rabbit paw does not interfere with its patency over a period of seven days

INTRODUÇÃO: A ecoescleroterapia com espuma (EEE) é um método minimamente invasivo de tratamento das varizes dos membros inferiores. Suas principais vantagens são a indicação para pacientes com alto risco cirúrgico, recuperação precoce pós-intervenção e menor custo inicial em relação aos outros métodos endovenosos. Porém, a taxa de oclusão venosa é variável, especialmente para o eixo venoso troncular com diâmetro maior que 6 mm. OBJETIVO: Comparar duas técnicas de EEE de polidocanol a 3% em veia safena magna (VSM) insuficiente, tendo como desfecho primário a taxa de sucesso completo com uma sessão terapêutica e desfechos secundários a avaliação da qualidade de vida e a taxa de complicações. PACIENTES E MÉTODOS: Seleção de 50 pacientes com varizes primárias superficiais em membro inferior (CEAP - classificação clínica, etiológica, anatômica, patofisiológica - C3) e insuficiência da VSM (6 - 10 mm de diâmetro) medida a 3 cm da junção safenofemoral. Trata-se de um estudo prospectivo, controlado e randomizado realizado no ambulatório do Serviço de Cirurgia Vascular e Endovascular do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Os participantes foram submetidos à EEE preparada pelo método de Tessari. No grupo controle, a injeção foi realizada com uma agulha 18G enquanto que, no grupo alvo, foi utilizado um cateter angiográfico multipurpose 4 Fr., precedendo-se à tumescência salina anestésica no compartimento da VSM, e irrigação contínua do cateter com solução salina antes da injeção da espuma esclerosante. A flebectomia das tributárias varicosas foi realizada em todos os pacientes em nível ambulatorial sob anestesia local tumescente. RESULTADOS: A EEE com cateter angiográfico, precedida de tumescência salina anestésica, com uma única sessão terapêutica, apresentou taxa de sucesso completo superior ao grupo controle (80% versus 36%) com significância estatística (p = 0,012). Houve melhora na qualidade de vida em ambos os grupos. (p < 0,001). Não houve diferença estatística entre os grupos na taxa de complicações (p = 0,584). CONCLUSÕES: A EEE com cateter longo em VSM, precedida de tumescência ecoguiada é um método seguro e eficaz. Apresenta maior taxa de sucesso completo da veia alvo com uma sessão terapêutica em comparação à técnica com cateter curto / INTRODUCTION: Foam echoesclerotherapy is a minimally invasive method to treat varicose veins of the legs. Its main advantages are indication for patients with high surgical risk, early recovery after intervention and lower initial cost in comparison to other endovenous methods. However, the vein occlusion rate is variable, notably for the truncal venous axis with diameter greater than 6 mm. OBJECTIVES: To compare two techniques of echoesclerotherapy with 3% polidocanol foam for the incompetent great saphenous vein (GSV), having as primary outcome the full success rate with one treatment session and secondary outcomes the quality of life and the complication rates. PATIENTS AND METHODS: Selection of 50 patients with primary superficial varicose veins of the leg (clinical, etiologic, anatomic, pathophysiologic - CEAP - classification C3) and GSV incompetence (6-10 mm diameter) measured at 3 cm distal from the saphenofemoral junction. This was a prospective, controlled and randomized trial conducted on the outpatient clinic, Division of Vascular and Endovascular Surgery, University of São Paulo. Patients underwent foam echoesclerotherapy prepared according to the Tessari method. In control group, the injection was performed with an 18G needle whereas in target group, a multipurpose angiographic catheter 4 Fr. was used, preceded by saline anaesthetic tumescence in the GSV compartment, and continuous catheter flush with saline solution before the sclerosing foam delivery. Phlebectomy of the varicose tributaries was performed under local tumescent anaesthesia on outpatient setting. RESULTS: Foam echoesclerotherapy with the angiographic catheter, preceded by saline anaesthetic tumescence yielded complete success rate with a single treatment session higher than the control group (80% versus 36%) with statistical significance (p = 0.012). There was improvement in quality of life in both groups (p < 0.001). There was no statistical difference between the groups in complication rates (p=0.584). CONCLUSIONS: Sclerotherapy with the long catheter, preceded of ultrasound-guided tumescence in the GSV compartment, is a safe and effective method. It yielded higher full success rate of the target vein with a single treatment session in comparison to the short catheter technique

Visage est l’une des meilleures biométries pour la reconnaissance de l’identité de personnes, car l’identification d’une personne par le visage est l’habitude instinctive humaine, et l’acquisition de données faciales est naturelle, non intrusive et bien acceptée par le public. Contrairement à la reconnaissance de visage par l’image 2D sur l’apparence, la reconnaissance de visage en 3D sur la forme est théoriquement plus stable et plus robuste à la variance d’éclairage, aux petits changements de pose de la tête et aux cosmétiques pour le visage. Spécifiquement, les courbures sont les plus importants attributs géométriques pour décrire la forme géométrique d’une surface. Elles sont bénéfiques à la caractérisation de la forme du visage qui permet de diminuer l’impact des variances environnementales. Cependant, les courbures traditionnelles ne sont définies que sur des surfaces lisses. Il est donc nécessaire de généraliser telles notions sur des surfaces discrètes, par exemple des visages 3D représenté par maillage triangulaire, et d’évaluer leurs performances en reconnaissance de visage 3D. En outre, même si un certain nombre d’algorithmes 3D FR avec une grande précision sont disponibles, le coût d’acquisition de telles données de haute résolution est difficilement acceptable pour les applications pratiques. Une question majeure est donc d’exploiter les algorithmes existants pour la reconnaissance de modèles à faible résolution collecté avec l’aide d’un nombre croissant de caméras consommateur de profondeur (Kinect). Le dernier problème, mais non le moindre, est la menace sur sécurité des systèmes de reconnaissance de visage 3D par les attaques de masque fabriqué. Cette thèse est consacrée à l’étude des attributs géométriques, des mesures de courbure principale, adaptées aux maillages triangulaires, et des schémas de reconnaissance de visage 3D impliquant des telles mesures de courbure principale. En plus, nous proposons aussi un schéma de vérification sur la reconnaissance de visage 3D collecté en comparant des modèles de résolutions hétérogènes équipement aux deux résolutions, et nous évaluons la performance anti-spoofing du système de RF 3D. Finalement, nous proposons une biométrie système complémentaire de reconnaissance veineuse de main basé sur la détection de vivacité et évaluons sa performance. Dans la reconnaissance de visage 3D par la forme géométrique, nous introduisons la généralisation des courbures principales conventionnelles et des directions principales aux cas des surfaces discrètes à maillage triangulaire, et présentons les concepts des mesures de courbure principale correspondants et des vecteurs de courbure principale. Utilisant ces courbures généralisées, nous élaborons deux descriptions de visage 3D et deux schémas de reconnaissance correspondent. Avec le premier descripteur de caractéristiques, appelé Local Principal Curvature Measures Pattern (LPCMP), nous générons trois images spéciales, appelée curvature faces, correspondant à trois mesures de courbure principale et encodons les curvature faces suivant la méthode de Local Binary Pattern. Il peut décrire la surface faciale de façon exhaustive par l’information de forme locale en concaténant un ensemble d’histogrammes calculés à partir de petits patchs dans les visages de courbure. Dans le deuxième système de reconnaissance de visage 3D sans enregistrement, appelée Principal Curvature Measures based meshSIFT descriptor (PCM-meshSIFT), les mesures de courbure principales sont d’abord calculées dans l’espace de l’échelle Gaussienne, et les extrèmes de la Différence de Courbure (DoC) sont définis comme les points de caractéristique. Ensuite, nous utilisons trois mesures de courbure principales et leurs vecteurs de courbure principaux correspondants pour construire trois descripteurs locaux pour chaque point caractéristique, qui sont invariants en rotation. [...] / Face is one of the best biometrics for person recognition related application, because identifying a person by face is human instinctive habit, and facial data acquisition is natural, non-intrusive, and socially well accepted. In contrast to traditional appearance-based 2D face recognition, shape-based 3D face recognition is theoretically more stable and robust to illumination variance, small head pose changes, and facial cosmetics. The curvatures are the most important geometric attributes to describe the shape of a smooth surface. They are beneficial to facial shape characterization which makes it possible to decrease the impact of environmental variances. However, exiting curvature measurements are only defined on smooth surface. It is required to generalize such notions to discrete meshed surface, e.g., 3D face scans, and to evaluate their performance in 3D face recognition. Furthermore, even though a number of 3D FR algorithms with high accuracy are available, they all require high-resolution 3D scans whose acquisition cost is too expensive to prevent them to be implemented in real-life applications. A major question is thus how to leverage the existing 3D FR algorithms and low-resolution 3D face scans which are readily available using an increasing number of depth-consumer cameras, e.g., Kinect. The last but not least problem is the security threat from spoofing attacks on 3D face recognition system. This thesis is dedicated to study the geometric attributes, principal curvature measures, suitable to triangle meshes, and the 3D face recognition schemes involving principal curvature measures. Meanwhile, based on these approaches, we propose a heterogeneous cross-resolution 3D FR scheme, evaluate the anti-spoofing performance of shape-analysis based 3D face recognition system, and design a supplementary hand-dorsa vein recognition system based on liveness detection with discriminative power. In 3D shape-based face recognition, we introduce the generalization of the conventional point-wise principal curvatures and principal directions for fitting triangle mesh case, and present the concepts of principal curvature measures and principal curvature vectors. Based on these generalized curvatures, we design two 3D face descriptions and recognition frameworks. With the first feature description, named as Local Principal Curvature Measures Pattern descriptor (LPCMP), we generate three curvature faces corresponding to three principal curvature measures, and encode the curvature faces following Local Binary Pattern method. It can comprehensively describe the local shape information of 3D facial surface by concatenating a set of histograms calculated from small patches in the encoded curvature faces. In the second registration-free feature description, named as Principal Curvature Measures based meshSIFT descriptor (PCM-meshSIFT), the principal curvature measures are firstly computed in the Gaussian scale space, and the extremum of Difference of Curvautre (DoC) is defined as keypoints. Then we employ three principal curvature measures and their corresponding principal curvature vectors to build three rotation-invariant local 3D shape descriptors for each keypoint, and adopt the sparse representation-based classifier for keypoint matching. The comprehensive experimental results based on FRGCv2 database and Bosphorus database demonstrate that our proposed 3D face recognition scheme are effective for face recognition and robust to poses and occlusions variations. Besides, the combination of the complementary shape-based information described by three principal curvature measures significantly improves the recognition ability of system. To deal with the problem towards heterogeneous cross-resolution 3D FR, we continuous to adopt the PCM-meshSIFT based feature descriptor to perform the related 3D face recognition. [...]

INTRODUÇÃO: O transplante hepático é o único tratamento efetivo para uma variedade de doenças hepáticas irreversíveis. No entanto, o número limitado de doadores pediátricos leva ao uso de enxertos hepáticos de doadores adultos, com necessidade de anastomoses vasculares mais complexas. Essas anastomoses tornam-se complicadas pela diferença no calibre dos vasos entre o doador e o receptor, resultando em alterações do fluxo sanguíneo, estenose da anastomose venosa ou arterial e trombose. Os efeitos para regeneração hepática decorrentes da privação do fluxo sanguíneo pela veia porta ou pela artéria hepática não estão completamente elucidados. Experimentalmente, quando um lobo do fígado não recebe o fluxo venoso portal, é observada atrofia deste segmento e hipertrofia do restante do órgão perfundido. Embora existam vários modelos experimentais para estudo da regeneração hepática, poucos são focados em animais em crescimento. Além disso, os efeitos regenerativos de drogas como o tacrolimus e a insulina precisam ser pesquisados, com o objetivo de encontrar um tratamento ideal para a insuficiência hepática ou um método de estimular a regeneração do fígado após ressecções ou transplantes parciais. O objetivo do presente estudo é descrever modelos de regeneração hepática em ratos em crescimento com: 1) ausência de fluxo hepático arterial e 2) redução do fluxo portal. Adicionalmente, o estudo avalia o efeito pró-regenerativo do tacrolimus e da insulina nesses modelos descritos. MÉTODOS: cento e vinte ratos (entre 50 e 100g de peso) foram divididos em 6 grupos, de acordo com o tipo de intervenção cirúrgica: Grupo 1, incisão abdominal sem intervenção hepática; Grupo 2, hepatectomia a 70%; Grupo 3, hepatectomia a 70% + estenose de veia porta; Grupo 4, hepatectomia a 70% + ligadura da artéria hepática; Grupo 5, hepatectomia a 70% + estenose de veia porta + insulina; Grupo 6, hepatectomia a 70% + estenose de veia porta + tacrolimus. Os animais dos grupos 1 ao 4 foram subdivididos em 5 subgrupos de acordo com o momento da morte: 1, 2, 3, 5 e 10 dias após a intervenção cirúrgica. Os animais dos grupos 5 e 6 foram subdividos em 2 subgrupos de acordo com o momento da morte: 2 e 10 dias após a intervenção cirúrgica. Os lobos hepáticos remanescentes foram submetidos à análise histomorfométrica, imuno-histoquímica e molecular. RESULTADOS: Verificou-se que no grupo com hepatectomia a 70% houve recuperação do peso do fígado no terceiro dia com aumento da atividade mitótica, enquanto que no grupo com estenose portal não se observou esse fenômeno (p < 0,001). A insulina e o tacrolimus promoveram aumento do peso do fígado e do índice mitótico. A atividade mitótica foi considerada aumentada nos animais dos grupos hepatectomia, hepatectomia + ligadura da artéria, insulina e tacrolimus; e esse parâmetro estava reduzido no grupo submetido à hepatectomia + estenose portal (p < 0,001). A expressão de interleucina 6 estava presente em todos os animais, sendo significativamente maior nos grupos hepatectomia, hepatectomia + ligadura da artéria e significativamente menor no grupo hepatectomia + estenose portal. Entretanto, a administração de tacrolimus ou insulina recuperou os níveis teciduais de interleucina 6 no grupo com estenose portal. CONCLUSÕES: No presente estudo foi padronizado um modelo simples e facilmente reprodutível para estudar a regeneração hepática em ratos em crescimento com redução do fluxo arterial ou venoso para o fígado. Foi demonstrado que a administração de insulina ou tacrolimus é capaz de reverter os efeitos deletérios da estenose portal na regeneração hepática. A obstrução do fluxo arterial não afetou a capacidade regenerativa hepática / BACKGROUND/PURPOSE: Liver transplantation is an effective treatment for a variety of irreversible liver diseases. However, the limited number of pediatric donor livers leads to the use of adult livers, which usually require more complex vascular anastomoses. These anastomoses are complicated by differences in vessel caliber between donors and recipients, resulting in vascular flow anomalies, stenosis of the venous or arterial anastomosis and thrombosis . The effects of portal vein or hepatic arterial flow privation in hepatic regeneration have not been completely elucidated. Experimentally, when a liver lobe is deprived of portal vein flow, atrophy is observed with hypertrophy of the other perfused parts of the organ, and interleukin-6 (IL-6) is required for normal liver regeneration. Although several experimental models are currently used to study the liver regeneration mechanisms, few studies have focused on the growing animal. In addition, the regenerative effects of drugs (e.g., tacrolimus and insulin) have been experimentally studied, aiming to find an ideal treatment for hepatic failure or a method of stimulating liver regeneration after extensive resection or partial transplants. The aim of the present investigation was to describe the new models of liver regeneration in growing rats with: 1) absence of arterial blood hepatic inflow and 2) reduced portal flow. Additionally, it was studied whether tacrolimus or insulin could have any pro-regenerative effect under such conditions. METHODS/MATERIALS: one hundred and twenty rats (50-100 g body weight) were divided into 6 groups based on the intervention type: Group 1 (sham), abdominal incision without intervention; Group 2, 70% hepatectomy; Group 3, 70% hepatectomy + portal vein stenosis; Group 4, 70% hepatectomy + ligation of the hepatic artery; Group 5, 70% hepatectomy + portal vein stenosis + insulin; and Group 6, 70% hepatectomy + portal vein stenosis + tacrolimus. Animals in groups 1 to 4 were subdivided into 5 groups according to the moment of death: 1, 2, 3, 5 and 10 days after surgical intervention. The animals in groups 5 and 6 were subdivided into 2 other groups according to the moment of death: 2 and 10 days after surgical intervention. The remnant liver lobes were harvested for morphological, histological histomorphometric, immunohistochemical and molecular analyses. RESULTS: it was verified that the hepatectomy group regained liver weight on the third day and had increased mitotic activity, and the portal vein stenosis prevented these phenomena, as well as the increased mitotic index (P < 0.001). In addition, insulin and tacrolimus promoted a significant increase of liver weight. Mitotic activity was considerably increased in the hepatectomy, hepatectomy + arterial ligature, insulin and tacrolimus groups and this parameter was reduced by portal vein stenosis. The expression of the interleukin-6 (IL-6) gene was present in all the animal groups. Tissue levels of IL- 6 were significantly increased by hepatectomy and hepatectomy + hepatic artery ligature; portal vein stenosis prevented this change. However, the administration of tacrolimus or insulin could recuperate the tissue levels of IL-6. CONCLUSION: In the present study a simple and highly reproducible model was standardized to study liver regeneration with portal vein or hepatic artery blood inflow reduction in growing rats. It was demonstrated that insulin or tacrolimus administration may partially reverse the harmful effects of portal vein stenosis. The obstruction of the arterial flow did not affect liver regeneration

INTRODUÇÃO: O transplante hepático é o único tratamento efetivo para uma variedade de doenças hepáticas irreversíveis. No entanto, o número limitado de doadores pediátricos leva ao uso de enxertos hepáticos de doadores adultos, com necessidade de anastomoses vasculares mais complexas. Essas anastomoses tornam-se complicadas pela diferença no calibre dos vasos entre o doador e o receptor, resultando em alterações do fluxo sanguíneo, estenose da anastomose venosa ou arterial e trombose. Os efeitos para regeneração hepática decorrentes da privação do fluxo sanguíneo pela veia porta ou pela artéria hepática não estão completamente elucidados. Experimentalmente, quando um lobo do fígado não recebe o fluxo venoso portal, é observada atrofia deste segmento e hipertrofia do restante do órgão perfundido. Embora existam vários modelos experimentais para estudo da regeneração hepática, poucos são focados em animais em crescimento. Além disso, os efeitos regenerativos de drogas como o tacrolimus e a insulina precisam ser pesquisados, com o objetivo de encontrar um tratamento ideal para a insuficiência hepática ou um método de estimular a regeneração do fígado após ressecções ou transplantes parciais. O objetivo do presente estudo é descrever modelos de regeneração hepática em ratos em crescimento com: 1) ausência de fluxo hepático arterial e 2) redução do fluxo portal. Adicionalmente, o estudo avalia o efeito pró-regenerativo do tacrolimus e da insulina nesses modelos descritos. MÉTODOS: cento e vinte ratos (entre 50 e 100g de peso) foram divididos em 6 grupos, de acordo com o tipo de intervenção cirúrgica: Grupo 1, incisão abdominal sem intervenção hepática; Grupo 2, hepatectomia a 70%; Grupo 3, hepatectomia a 70% + estenose de veia porta; Grupo 4, hepatectomia a 70% + ligadura da artéria hepática; Grupo 5, hepatectomia a 70% + estenose de veia porta + insulina; Grupo 6, hepatectomia a 70% + estenose de veia porta + tacrolimus. Os animais dos grupos 1 ao 4 foram subdivididos em 5 subgrupos de acordo com o momento da morte: 1, 2, 3, 5 e 10 dias após a intervenção cirúrgica. Os animais dos grupos 5 e 6 foram subdividos em 2 subgrupos de acordo com o momento da morte: 2 e 10 dias após a intervenção cirúrgica. Os lobos hepáticos remanescentes foram submetidos à análise histomorfométrica, imuno-histoquímica e molecular. RESULTADOS: Verificou-se que no grupo com hepatectomia a 70% houve recuperação do peso do fígado no terceiro dia com aumento da atividade mitótica, enquanto que no grupo com estenose portal não se observou esse fenômeno (p < 0,001). A insulina e o tacrolimus promoveram aumento do peso do fígado e do índice mitótico. A atividade mitótica foi considerada aumentada nos animais dos grupos hepatectomia, hepatectomia + ligadura da artéria, insulina e tacrolimus; e esse parâmetro estava reduzido no grupo submetido à hepatectomia + estenose portal (p < 0,001). A expressão de interleucina 6 estava presente em todos os animais, sendo significativamente maior nos grupos hepatectomia, hepatectomia + ligadura da artéria e significativamente menor no grupo hepatectomia + estenose portal. Entretanto, a administração de tacrolimus ou insulina recuperou os níveis teciduais de interleucina 6 no grupo com estenose portal. CONCLUSÕES: No presente estudo foi padronizado um modelo simples e facilmente reprodutível para estudar a regeneração hepática em ratos em crescimento com redução do fluxo arterial ou venoso para o fígado. Foi demonstrado que a administração de insulina ou tacrolimus é capaz de reverter os efeitos deletérios da estenose portal na regeneração hepática. A obstrução do fluxo arterial não afetou a capacidade regenerativa hepática / BACKGROUND/PURPOSE: Liver transplantation is an effective treatment for a variety of irreversible liver diseases. However, the limited number of pediatric donor livers leads to the use of adult livers, which usually require more complex vascular anastomoses. These anastomoses are complicated by differences in vessel caliber between donors and recipients, resulting in vascular flow anomalies, stenosis of the venous or arterial anastomosis and thrombosis . The effects of portal vein or hepatic arterial flow privation in hepatic regeneration have not been completely elucidated. Experimentally, when a liver lobe is deprived of portal vein flow, atrophy is observed with hypertrophy of the other perfused parts of the organ, and interleukin-6 (IL-6) is required for normal liver regeneration. Although several experimental models are currently used to study the liver regeneration mechanisms, few studies have focused on the growing animal. In addition, the regenerative effects of drugs (e.g., tacrolimus and insulin) have been experimentally studied, aiming to find an ideal treatment for hepatic failure or a method of stimulating liver regeneration after extensive resection or partial transplants. The aim of the present investigation was to describe the new models of liver regeneration in growing rats with: 1) absence of arterial blood hepatic inflow and 2) reduced portal flow. Additionally, it was studied whether tacrolimus or insulin could have any pro-regenerative effect under such conditions. METHODS/MATERIALS: one hundred and twenty rats (50-100 g body weight) were divided into 6 groups based on the intervention type: Group 1 (sham), abdominal incision without intervention; Group 2, 70% hepatectomy; Group 3, 70% hepatectomy + portal vein stenosis; Group 4, 70% hepatectomy + ligation of the hepatic artery; Group 5, 70% hepatectomy + portal vein stenosis + insulin; and Group 6, 70% hepatectomy + portal vein stenosis + tacrolimus. Animals in groups 1 to 4 were subdivided into 5 groups according to the moment of death: 1, 2, 3, 5 and 10 days after surgical intervention. The animals in groups 5 and 6 were subdivided into 2 other groups according to the moment of death: 2 and 10 days after surgical intervention. The remnant liver lobes were harvested for morphological, histological histomorphometric, immunohistochemical and molecular analyses. RESULTS: it was verified that the hepatectomy group regained liver weight on the third day and had increased mitotic activity, and the portal vein stenosis prevented these phenomena, as well as the increased mitotic index (P < 0.001). In addition, insulin and tacrolimus promoted a significant increase of liver weight. Mitotic activity was considerably increased in the hepatectomy, hepatectomy + arterial ligature, insulin and tacrolimus groups and this parameter was reduced by portal vein stenosis. The expression of the interleukin-6 (IL-6) gene was present in all the animal groups. Tissue levels of IL- 6 were significantly increased by hepatectomy and hepatectomy + hepatic artery ligature; portal vein stenosis prevented this change. However, the administration of tacrolimus or insulin could recuperate the tissue levels of IL-6. CONCLUSION: In the present study a simple and highly reproducible model was standardized to study liver regeneration with portal vein or hepatic artery blood inflow reduction in growing rats. It was demonstrated that insulin or tacrolimus administration may partially reverse the harmful effects of portal vein stenosis. The obstruction of the arterial flow did not affect liver regeneration

Retinal imaging enables the visualization of a portion of the human microvasculature in-vivo and non-invasively. The scanning laser ophthalmoscope (SLO), provides images characterized by an ultra-wide field of view (UWFoV) covering approximately 180-200º in a single scan, minimizing the discomfort for the subject. The microvasculature visible in retinal images and its changes have been vastly investigated as candidate biomarkers for different types of systemic conditions like cardiovascular disease (CVD), which currently remains the main cause of death in Europe. For the CARMEN study, UWFoV SLO images were acquired from more than 1,000 people who were recruited from two studies, TASCFORCE and SCOT-HEART, focused on CVD. This thesis presents an automated system for SLO image processing and computation of candidate biomarkers to be associated with cardiovascular risk and MRI imaging data. A vessel segmentation technique was developed by making use of a bank of multi-scale matched filters and a neural network classifier. The technique was devised to minimize errors in vessel width estimation, in order to ensure the reliability of width measures obtained from the vessel maps. After a step of refinement of the centrelines, a multi-level classification technique was deployed to label all vessel segments as arterioles or venules. The method exploited a set of pixel-level features for local classification and a novel formulation for a graph cut approach to partition consistently the retinal vasculature that was modelled as an undirected graph. Once all the vessels were labelled, a tree representation was adopted for each vessel and its branches to fully automate the process of biomarker extraction. Finally, a set of 75 retinal parameters, including information provided by the periphery of the retina, was created for each image and used for the biomarker investigation.