Submitted by Nadir Basilio (nadirsb@uninove.br) on 2018-07-17T21:13:23Z No. of bitstreams: 1 Jessica Julioti Urbano.pdf: 3065396 bytes, checksum: 1e38f15e601296f027d3fd4cd280d051 (MD5) / Made available in DSpace on 2018-07-17T21:13:23Z (GMT). No. of bitstreams: 1 Jessica Julioti Urbano.pdf: 3065396 bytes, checksum: 1e38f15e601296f027d3fd4cd280d051 (MD5) Previous issue date: 2016-11-30 / The actual scientific approach to bioengineering organs is based on the use of natural extracellular matrix of decellularized lung as initial departure for subsequent reconstruction of the organ for recellularization in a bioreactor. The decellularization technique can be performed by two infusion ways, one through the trachea and other by pulmonary artery. The aim of this studies was to investigate in an experimental animal model, by the occlusion at the end of inspiration (OEI) and movement equation (ME), the behavior of the elastic, viscous and viscoelastic mechanical properties, of mice lungs after the process of decellularization through the trachea and the pulmonary artery. Were used 30 male mice C57BL/6, weighing 17-18 g (7-8 weeks of age), anesthetized and euthanized by exsanguination through the abdominal aorta. The decellularization protocol comprised the following steps: collecting, cleaning, freezing and thawing, rinsing with sodium dodecyl sulfate and phosphate buffered saline. For the studies I and II, the lungs were divided into the control group (GC = 10), the decellularization group by the trachea (TDG = 10) and the pulmonary artery decellularization group (PDG = 10), 5 lungs in each group for the study I that had the analysis through the technique of OEI and 5 lungs in each group for the study II with analysis through the ME. In the study I, the values of static elastance (Eest = CG: 226.9 ± 4.1, PDG: 162.6 ± 3.9, TDG: 154.8 ± 1.7) and dynamics (Edyn = CG: 240 , 9 ± 6.7, PDG: 176 ± 5.4, TDG: 177.6 ± 1.6) were significantly lower in TDG and PDG when compared to CG. In study II, the value of lung resistance presented in TDG was significantly lower in relation to the other two groups (R = CG: 5.32 ± 0.26; PDG: 5.94 ± 0.24; TDG: 2.85 ± 0.14) and GC elastance was significantly higher in comparison with TDG and PDG, and in PDG the difference was significantly lower in relation to TDG (E = CG: 279 ± 13.81; PDG: 146 ± 19.04, TDG: 209.6 ± 12.06). We can observe in both the two-way decellularization are effective to provide a scaffold ideal for pulmonary later recellularization when evaluated by the OEI and ME. Furthermore, the decellularized lungs through the pulmonary artery may be used to create a pulmonary scaffold in less time, because the protocol can be performed in a day, which facilitates the process for obtaining functional lungs scaffolds. / A abordagem científica atual para a bioengenharia de órgãos é baseada na utilização da matriz extracelular natural do pulmão descelularizado como partida inicial para posterior reconstrução do órgão por recelularização em um biorreator. A técnica de descelularização pode ser realizada por duas vias de perfusão, uma através da traqueia e a outra pela artéria pulmonar. O objetivo deste estudo foi investigar em um modelo experimental animal, através da técnica de oclusão ao final da inspiração (OFI) e equação do movimento (EM), o comportamento das propriedades mecânicas elásticas, viscosas e viscoelásticas de pulmões descelularizados de camundongos pelos métodos de perfusão através da traqueia e da artéria pulmonar. Foram utilizados 30 camundongos machos da raça C57BL/6, com peso de 17-18 g (7-8 semanas de idade), anestesiados e eutanasiados por exsanguinação pela aorta abdominal. O protocolo de descelularização seguiu as etapas de coleta, limpeza, congelamento e descongelamento, lavagem com dodecil-sulfato de sódio e tampão fosfato-salino. Para a realização dos estudos I e II, os pulmões foram divididos em grupo controle (GC = 10), grupo descelularização pela traqueia (TDG = 10) e grupo descelularização pela artéria pulmonar (PDG = 10), sendo 5 pulmões em cada grupo para o estudo I que teve a análise através da técnica de OFI e 5 pulmões em cada grupo para o estudo II com análise através da EM. No estudo I, os valores de elastância estática (Eest = CG: 226,9 ± 4,1; PDG: 162,6 ± 3,9; TDG: 154,8 ± 1,7) e dinâmica (Edyn = CG: 240,9 ± 6,7; PDG: 176 ± 5,4; TDG: 177,6 ± 1,6) foram significativamente menores em TDG e PDG quando comparados com o CG. Já no estudo II, o valor da resistência pulmonar apresentado no TDG foi significativamente menor em relação aos outros dois grupos (R = CG: 5,32 ± 0,26; PDG: 5,94 ± 0,24; TDG: 2,85 ± 0,14) e o valor da elastância de CG apresentou-se maior de forma significativa em comparação com a TDG e PDG, e no PDG a diferença foi menor significativamente em relação à TDG (E = CG: 279 ± 13,81; PDG: 146 ± 19,04; TDG: 209,6 ± 12,06). Podemos observar que, quando avaliadas pelas técnicas de OFI e EM, as duas vias de descelularização foram eficazes na geração de um scaffold pulmonar ideal para posterior recelularização. Além disso, a técnica de descelularização através da artéria pulmonar mostrou-se eficaz para a obtenção de um scaffold pulmonar em menor período de tempo, uma vez que o protocolo pode ser realizado em um dia, o que facilita o processo de obtenção de pulmões funcionais.

Introdução. A elevação dos marcadores inflamatórios e de necrose miocárdica, após intervenção coronária percutânea, pode interferir nos resultados clínicos. No entanto, pouco se conhece sobre a terapia com estatinas pré-procedimento na redução destes marcadores em pacientes estáveis de baixo risco. Objetivo. Avaliar se o uso de estatina, antes do implante eletivo de stent coronário (ISC), reduz os níveis plasmáticos de marcadores inflamatórios e de necrose miocárdica, em pacientes com doença arterial coronária (DAC), estáveis e de baixo risco. Métodos. Neste estudo observacional prospectivo, 100 pacientes (n=50 em uso de estatina vs n=50 sem uso de estatina) com DAC estável foram submetidos à implante eletivo de stent coronário. Marcadores inflamatórios (proteína C reativa [PCR], interleucina[IL] -6, fator de necrose tumoral- e matrix metaloproteinase-9) e marcadores de necrose miocárdica (troponina I e CK-MB ) foram dosados antes e 24 horas após o implante eletivo de stent coronário. Resultados. Todos os pacientes apresentaram um aumento significativo de PCR e IL-6, após ISC. No entanto, esse aumento foi anulado em pacientes que faziam uso de estatina antes de ISC em relação àqueles que não tomavam estatina: 75% vs 150% (p <0,001) e 192% vs 300% (p <0,01) respectivamente. Os outros marcadores pró-inflamatórios foram semelhantes para os dois grupos de pacientes. Troponina I e CK-MB não se alterou, após ISC, independentemente, da terapia com estatina anterior ou não. Conclusão. O pré-tratamento com estatina reduz a magnitude da inflamação após ISC, demonstrada por aumentos significativamente menores de PCR e IL-6, em pacientes com DAC, estável e de baixo risco. Lesão miocárdica periprocedimento foi irrelevante e não foi afetada pela terapia com estatina pré-procedimento nesta população / Background. The elevation of markers of inflammatory and myocardial necrosis after percutaneous coronary intervention may interfere on clinical outcome. However, little is known concerning preprocedural statin therapy on the reduction of these markers in stable patients at low-risk. Objective. To evaluate if statin therapy prior to elective coronary stent implantation (CSI) reduces the plasma levels of markers inflammatory and myocardial necrosis in patients with low-risk stable coronary artery disease (CAD). Methods. In this prospective, observational study, 100 patients (n=50 on statin therapy vs n=50 not on statin) with stable CAD underwent elective CSI. Inflammatory (C-reactive protein [CRP], interleukin [IL]-6, tumor necrosis factor-a and matrix metalloproteinase-9) and myocardial necrosis markers (troponin I and CK-MB) were determined before and 24 hours after CSI. Results. All patients presented a significant increase of CRP and IL-6 after CSI. However, this increase was blunted in patients on statin therapy prior to CSI than those without statin therapy: 75% vs 150% (p<0.001), and 192% vs 300% (p<0.01), respectively for PCR and IL-6. The other pro-inflammatory markers were not affected in both sets of patients. Troponin I and CK-MB did not change after CSI regardless of previous statin therapy or not. Conclusions. Previous treatment with statins reduces the magnitude of procedural inflammation, denoted by markedly lower increases of CRP and IL-6 levels, in elective CSI on stable CAD patients. Periprocedural myocardial injury was not significant in this population

High anxiety is associated with an increased risk of developing cardiovascular disease (CVD), in particular, atherosclerotic coronary artery disease. However, the mechanisms by which anxiety contributes to the development of CVD are unclear. Unlike other common psychiatric disorders such as depression, anxiety and its effects on CVD risk has not been studied extensively. Moreover, whether elevated anxiety is associated with arterial stiffness and vascular endothelial dysfunction, biomarkers of CVD risk, in healthy adults and whether a psychological intervention designed to lower anxiety levels in healthy adults with moderate to high baseline anxiety levels ameliorates vascular dysfunction remains unclear. The purpose of this study was twofold; first to determine the extent to which moderate to high anxiety levels are associated with vascular dysfunction including aortic stiffness as measured by carotid-femoral pulse wave velocity (cf-PWV), carotid artery stiffness via ultrasound-based β-stiffness index, and forearm resistance artery function measured as peak forearm blood flow using venous occlusion plethysmograph (VOP). Secondly, to determine whether the empirically validated Acceptance and Commitment Training (ACT) anxiety intervention improved vascular function after 12 weeks and if this was associated with reductions in anxiety in adults with moderate to high baseline anxiety levels. Our results indicated that there was no association between increased anxiety levels and any of the three vascular outcomes of interest. Conversely, there was an association between the ACT intervention participation and improvement in forearm resistance artery function independent of age, sex, education, race/ethnicity, BMI and STAI Trait anxiety. Taken together, these data suggest that although higher State and Trait anxiety was not associated with aortic stiffness, carotid stiffness or forearm resistance artery function, and the ACT intervention was associated with improved peripheral resistance artery function. Additional studies are needed to determine whether this effect occurs earlier than 12 weeks and sustained longer that 12 weeks, and whether it occurs in adults with CVD risk factors (i.e. atherosclerosis), non-white racial/ethnic backgrounds and in resistance vessel function in response to intra-arterial vasoactive agonists such as acetylcholine.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22744号 / 医博第4662号 / 新制||医||1046(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 髙折 晃史, 教授 竹内 理, 教授 近藤 玄 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23057号 / 医博第4684号 / 新制||医||1048(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 森田 智視, 教授 湊谷 謙司, 教授 川上 浩司 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Background: Glycation influences the ultrastructure and clot kinetics of fibrin clots due to the post-translational modifications in fibrinogen. Methylglyoxal (MG) is used to measure the level of glycation which has been associated with the pathogenesis of type 2 diabetes Melilites (T2DM) and coronary heart disease (CHD). The aim of the study was to determine the role of MG on clot kinetics and fibrin clot structure in CHD patients with and without T2DM to provide insight into the mechanism of pathogenesis of atherosclerosis in T2DM which results in the development of CHD. Methodology: Scanning electron microscopy (SEM) was used to evaluate the morphology of fibrin clots. Thromboelastography (TEG) was used to assess the physiological clot properties (kinetics). Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of methylglyoxal-adducts. Results: The morphology of clots from controls analysed using SEM showed thick and thin fibres which created an organised mesh of fibrin fibres. In T2DM, CHD with T2DM and CHD some alterations in the morphology were observed. The ultrastructure micrographs in CHD shows that some of the fibrin fibres formed have individual fibres with both thick and thin fibres as well as a thick mass of fibres with a net-like structure that forms dense-matted deposits. In addition, the fibrin fibres are not organised. The densitometry analysis between controls and patient groups’ (CHD: mean (standard deviation) 0.42±0.11; CHD+T2DM: 0.31±0.08 and T2DM: 0.29±0.08) was found to be significantly lower in all groups compared to the control which had a mean of 0.57±0.1, p<0.0001. There are no significant differences in the alpha angle between CHD, T2DM, CHD with T2DM and controls (60.88±2.321˚ vs. 60.81±2.385˚ vs. 59.09± 3.185˚ vs. 66.47±1.300˚, p=0.5279). There was no significant difference found in the K-value between T2DM, CHD with T2DM, CHD and control subjects (3.458±0.446mins vs. 5.118±1.589mins vs. 3.758±0.450mins vs. 2.839±0.2156mins, p=0.0102). The maximum amplitude was higher in T2DM patients compared to CHD, CHD with T2DM and controls (40.51±1.914mm vs. 34.10±2.127mm vs. 33.12±3.365mm vs. 33.60±1.525mm, p=0.0102). The MRTG was higher in CHD compared to T2DM, CHD 4 with T2DM and controls (10.74±3.335 dyn cm-2 s -1 vs. 4.268±0.690 dyn cm-2 s -1 vs. 5.046± 0.927 dyn cm-2 s -1 vs. 6.535±0.664 dyn cm-2 s -1 , p=0.0096). The reaction time was higher in CHD with T2DM patients compared to T2DM, CHD and controls (32.58±4.005min vs. 23.92±2.793min vs. 21.29± 2.383min vs. 8.322±0.886min, p<0.0001). There was no significant difference found in the TTG between T2DM, CHD with T2DM, CHD and control subjects (231.3±28.68 dyn cm-2 vs. 258.5±38.15 dyn cm2 vs. 343.7±71.92 dyn cm-2 vs. 287.7±21.37 dyn cm-2 , p=0.8421). The TMRTG was higher in T2DM patients compared to T2DM, CHD with T2DM, CHD and controls (23.91±2.409mins vs. 20.46±3.411mins vs. 14.14±1.287mins vs. 10.16±0.751mins, p<0.0001). To assess if an association between MG-adducts and clot kinetics exists, the Spearman r correlation was completed for each clot parameter. The reaction time (p=0.0047, 95% CI: 0.138 to 0.665) and time taken before maximum speed of the clot growth to be achieved (p=0.3958, 95% CI: 0.072 to 0.644) was significant. This indicates the relationship between the parameters i.e., the higher the level of MGadducts present, the longer it takes for clotting to begin and reach maximum speed of formation. Conclusion: This study showed that there are ultrastructural differences in fibrin fibres formed in CHD patients with T2DM. The viscoelastic parameters indicated that haemostasis was irregular in CHD and T2DM. The levels of MG-adducts were much higher in T2DM, CHD with T2DM and CHD and may be a contributing factor to the pathogenesis associated with altered coagulation in these patients. / Dissertation (MSc (Physiology))--University of Pretoria, 2020. / NRF / Physiology / MSc (Physiology) / Unrestricted

京都大学 / 新制・論文博士 / 博士(医学) / 乙第13435号 / 論医博第2234号 / 新制||医||1054(附属図書館) / (主査)教授 石見 拓, 教授 佐藤 俊哉, 教授 湊谷 謙司 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

The thesis deals with measurements of the atherosclerothic carotid plaques mechanical properties with wiew towards the improvements of their constitutive models and then towards the impact of application of those constitutive models in fibrous cap. The introductory part provides a brief summary of medical knowledge needed to understand atheroma formation and the risks involved. Next, there's a survey of plaque mechanical testing methods and the obtained results on tissue properties. The previously used constitutive models of atherosclerothic tissues are listed as well. Main body of the thesis describes the preparation of testing samples from obtained atheroma, methodology and course of experiments execution and subsequent processing of the experimental data to evaluate the behavior of the atheromatous tissue individual parts. Then the discussion and evaluation of our results and findings is given. Along with the evaluated mechanical properties, experimental data fitted to models are presented with respect to their predictive abilities. The final part is dedvoted to the finite element analysis of an idealized 2D model with emphasis on the effect of necrotic core and fibrous tissue properties on von Mises equivalent stress in the fibrous cap.

This diploma thesis is focused on detection in images using extended set of Haar-like features and histogram-based method. At first is introduced a basic concept of extraction and classification image features. The next part bring own concept of image features based on Diffusion distance. Result of this work is implementation this methods in Rapidminer.

This thesis deals with the computational solution of stress-strain states in the vicinity of the connection (anastomosis) between artery and vascular replacement. An „end to end“ anastomosis loaded by inner light increased constant systolic blood pressure is modeled in the thesis. The connection is modeled by different variants of the bonded contact and attachment of a surgical stitch. To solve the stress-strain state constitutive models were used in the finite element software package ANSYS 13.0. Material properties of arteries and vascular grafts were taken from measurements made at the Institute of solid mechanics, mechatronics and biomechanics.