INTRODUÇÃO: Diferentes parâmetros hemodinâmicos, incluindo os indicadores estáticos de pré-carga cardíaca como o índice de volume diastólico final ventrículo direito (IVDFVD) e parâmetros dinâmicos como a variação de pressão de pulso (VPP) têm sido usados na tomada de decisão para considerar o processo da expansão volêmica em pacientes em estado grave. O objetivo deste estudo foi comparar a reanimação por fluidos guiados tanto por VPP ou IVDFVD após choque hemorrágico induzido experimentalmente. MÉTODO: vinte e seis suínos anestesiados e ventilados mecanicamente foram alocados em três grupos: controle (Grupo I), VPP (Grupo II) e IVDFVD (Grupo III). Foi induzido choque hemorrágico por retirada de sangue até atingir a pressão arterial média de 40mmhg, que foi mantida por 60 minutos. Parâmetros foram medidos no tempo basal (B), no tempo do choque (Choque 0), sessenta minutos depois do choque (Choque 60), imediatamente depois da ressuscitação com hidroxietilamido 6% (130/0. 4) (R0), uma hora (R60) e duas horas (R120) depois ressuscitação. Os pontos de avaliação da reanimação por fluidos foram determinados pelo retorno aos valores basais iniciais de VPP e IVDFVD. A análise estatística dos dados foi baseada em ANOVA para medidas repetidas seguidos pelo teste de Bonferroni (P<0.05%). RESULTADOS: O volume e tempo para ressuscitação foram maiores no grupo III do que no grupo II (Grupo III = 1305±331ml e Grupo II = 965±245ml; p<0.05 e Grupo III = 24.8± 4.7min e Grupo II = 8.8 ± 1.3 min, p<0.01, respectivamente). Todos os parâmetros estáticos e dinâmicos, bem como os biomarcadores de oxigenação tecidual foram afetados pelo choque hemorrágico e quase todos os parâmetros foram totalmente restaurados após a reanimação em ambos os grupos. CONCLUSÃO: Neste estudo em modelo de choque hemorrágico, a reanimação guiada pelo VPP utilizou menor quantidade de fluido e menor quantidade de tempo do que quando guiado por IVDFVD derivado de cateter de artéria pulmonar. / INTRODUCTION: Different hemodynamic parameters, including static indicators of cardiac preload as right ventricular end-diastolic volume index (RVEDVI) and dynamic parameters as pulse pressure variation (PPV) have been used in the decision-making process regarding volume expansion in critically ill patients. The objective of this study was to compare fluid resuscitation guided by either PPV or RVEDVI after experimentally-induced hemorrhagic shock. METHODS: 26 anesthetized and mechanically ventilated pigs were allocated into control (Group-I), PPV (Group-II) and RVEDVI (Group- III). Hemorrhagic shock was induced by blood withdrawal to target mean arterial pressure of 40mmHg, maintained for 60 minutes. Parameters were measured at baseline, time of shock, sixty minutes after shock, immediately after resuscitation with hydroxyethyl starch 6% (130/0.4), one hour and two hours thereafter. The endpoint of fluid resuscitation was determined as the baseline values of PPV and RVEDVI. Statistical analysis of data was based on ANOVA for repeated measures followed by the Bonferroni test (P<0.05). RESULTS: Volume and time to resuscitation were higher in Group-III than in Group-II (Group-III = 1305±331ml and Group-II = 965±245ml; p<0.05 and Group-IIII = 24.8±4.7min and Group-II = 8.8±1.3 min, p<0.05, respectively). All static and dynamic parameters and biomarkers of tissue oxygenation were affected by hemorrhagic shock and nearly all parameters were restored after resuscitation in both groups. CONCLUSION: In the proposed model of hemorrhagic shock, resuscitation to the established endpoints was achieved within a smaller amount of time and with less volume when guided by PPV than when guided by pulmonary artery catheter-derived RVEDVI.

Metais são largamente empregados em implantes (endopróteses), principalmente nos que tem finalidade ortopédica. O meio fisiológico representa um meio extremamente agressivo, provocando corrosão que pode resultar em sérios problemas aos pacientes que recebem os implantes. Passou-se a utilizar revestimentos sobre o metal-base de implantes para melhorar a sua resistência à corrosão. Mais recentemente, revestimentos porosos de cerâmica, que permitem ao tecido ósseo um crescimento por entre a porosidade, passaram a ser empregados, pois assim dispensam o uso de cimentos acrílicos na fixação da prótese ao osso. A hidroxiapatita (HA) é um dos revestimentos cerâmicos cuja aplicação comercial tem crescido bastante, principalmente em cirurgias de substituição total de quadril (total hip replacement). A corrosão eletroquímica em metais comumente empregados em endopróteses e que aceitam o revestimento de hidroxiapatita (aços inox F138 grau 2, 316L grau 1 e liga Co-Cr-Mo F75)foi estudada, de forma a determinar se este tipo de revestimento influi ou não na corrosão. Através de testes, e análises metalográficas e de microscopia eletrônica de varredura, foi analisada a corrosão destes materiais em dois meios fisiológicos (Soro Bovino e Soro Fisiológico), comparando-se os resultados obtidos com e sem revestimento de hidroxiapatita. / MetaIs are widely used in implants (endoprostheses), mainly in orthopedic ones. The physiologic solution is very aggressive, and promote the metal corrosion, that may drive the patient that receive the implant to serious complications. Coatings over the base metal are being applied to improve the corrosion resistance. Recently, ceramic porous-coating began to be used. This kind of coating allows the bone tissue to ingrowth into the pores of HA-coated, and so avoid the use of acrylic cements do bind the protesis to the bone. The hidroxiapatite (HA) is one of the ceramic coatings that the commercial use have been growing, mainly in total hip replacement surgeries. The Electro-Chemical corrosion in the most common metaIs used in endoprostheses, that accept the HA-coat was studied (stainless steels F138 grade 1 and 316L grade 2 and F75 Co-Cr-Mo alloy). By this way, this study aimed to tell if the HA-coat has any influence in the corrosion rate. Trough chemical-electro corrosion tests, and metallographies, and electronic microscopy, the corrosion of these metaIs was analyzed in two different physiologic solutions, confronting the results between HA-coated and non coated samples. Coated samples had, in both solutions, a lower corrosion rate. The bovine solution was more agressive between non coated samples. But fisiologic solution was more agressive with coated samples. Between coated samples, F75 alloy had the lower corrosion rate. But F138 stainless steel without coating was the less corroded.

This diploma thesis deals with experiencing emotions and emotional habituation. The aim of the work was to compare changes in subjectively felt intensity of emotional experience and physiological responses during repeated affective stimulation. In the theoretical part were presented the concepts of affective experience and emotional habituation, their biological basis and methods of investigation. The empirical part is devoted to an experiment in which sets of positive and negative picture (IAPS database) and sets of videos in different order were repeatedly presented to group of 124 people. During the presentation were observed changes in subjective evaluation of stimuli and in physiological responses (skin conductance, skin temperature). The habituation process has been tested with regard to the order of stimuli. The results demonstrated that habituation process were present at a subjective level. Also habituation process occured for the physiological indicator, the skin temperature in the part of group that saw for the first stimulus set of positive videos. The habituation of skin conductance did not appear, on the contrary its values increase with a series of repetitions. There is some probability, that subjective and physiological habituation are independent to each other. Previous affective...

The prevalence and devastating nature of cardiovascular diseases has led to many advancements in the therapies used to treat the millions of patients that suffer as a result of these conditions. As coronary artery disease (CAD) is the most common of these cardiovascular conditions, it is a major focus of research among the medical industry. Although lifestyle changes and drug therapies can treat early CAD, more advanced cases often require more definitive interventions. In conjunction with angioplasty, stenting of an occluded vessel has shown significant success in preventing restenosis. However, as with nearly every therapeutic process in the medical field, several complications have arisen in stented patients that pose a need for further improvement of the devices. As a result, the stent industry is constantly striving towards improving the characteristics and outcome of their product and with these efforts comes the need for extensive testing and research. Continuous improvement and innovation in the field of tissue engineering has brought about the possibility of creating laboratory grown tissue engineered vascular grafts (TEVGs) for the purpose of replacing and/or bypassing damaged or occluded regions of the vasculature. By employing the techniques used to produce TEVGs, a blood vessel mimic (BVM) bioreactor system has been developed with the intent of using the resulting construct as a model for testing the cellular response of a human blood vessel to an intravascular device such as a stent. This would allow gathering of more significant data in the early stages of device development and may reduce the overall costs and time required to refine a design. Although the BVM system has previously been used to cultivate viable constructs that were subsequently used to observe the response to a deployed stent, the flow conditions within the original design are not representative of the physiologic conditions in a native vessel. This aspect of the original system presented a need for development in order to be considered by researchers as an accurate in vitro representation of the target vessels in which the stents are used. One of the primary concerns of this environment is creating and maintaining physiologic flow conditions that will represent those present in native vessels in order to facilitate cells sodded on the construct to grow as they would under native conditions. The two key aspects of flow are pulsatility and wall shear stress. Studies in this thesis were carried out to determine the best and most feasible methods for implementing appropriate levels of pulsation and wall shear stress in the previously established BVM bioreactor system with the intention of maintaining the original system’s simplicity and high throughput potential. Pulsatile flow was created by elevating backpressure in the BVM chamber while using a different pump head and pump tubing. Wall shear stress was adjusted by altering the viscosity of the perfusate and flow rate through the system. Both pulsatile flow and shear stress were established without any major changes to the overall configuration of the system. Pulsatile pressures of ~80 mmHg and wall shear stress forces of ~6.4 dyn/cm2 were established with minimal alteration to the original system. Pulsatility was created by using a 3-roller peristaltic pump head in place of the originally specified 8-roller head to create pulses that were then regulated with backpressure created by restricting down stream flow. Increasing the viscosity and corresponding flow rate allowed for instigation and control of wall shear stress at the inner wall of the BVM graft. Although the resulting protocols presented here require refinement for ultimately successful implementation, they are important underpinnings that will facilitate the eventual development of an ideal BVM system that is highly suitable for use as a high-throughput intravascular device testing model.

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There are limited methods of assessing pulmonary function in horses at rest. In this study, we developed clinical techniques to measure gas exchange efficiency in horses. These techniques were then used to evaluate horses with varying degrees of lower respiratory disease. Three groups of horses (Group 1: asymptomatic, n=6; Group 2: symptomatic only with rebreathing, n=11; Group 3: symptomatic at rest, n=9) were selected based on physical exam, transtracheal aspirate, and thoracic radiographs. Blood samples were obtained from the transverse facial artery and jugular vein. Maximal end-tidal CO₂ tension (E_TCO₂) was measured by an infrared capnograph through a facemask. Alveolar O, tension, alveolar dead space fraction (V_DB/V_T), and physiologic shunt fraction (Q_S/Q_T) were calculated using standard formulas. Horses with both mild and severe signs of lower respiratory disease had significant (p<0.05) differences in gas exchange indices at rest compared to asymptomatic horses. Albuterol was administered to seven of the Group 2 horses from a metered-dose inhaler through an equine facemask at a dose of 90 μg per 100 kg. Blood samples and tidal gas samples were obtained 15 minutes post-treatment, and Q_S/Q_T and (V_DB/V_T) were calculated. Albuterol caused significant (p<0.05) hypoxemia 15 minutes following inhaled administration. This was accompanied by a significant increase in Q_S/Q_T, suggesting that the hypoxemia was due to increases in which the ratios of ventilation to perfusion were decreased. / Master of Science

Le facteur VIII (FVIII) est une glycoprotéine de la coagulation plasmatique, co-facteur du facteur IX activé (FIXa). Son métabolisme dépend de multiples facteurs limitant ou favorisant sa survie ou sa fonction. L’objectif de ce travail était d’analyser les différents paramètres pouvant influencer le taux de FVIII circulant et sa fonction pro-coagulante. Il a compris 4 volets : 1) Nous avons montré que la rétention intra-cellulaire connue du FVIII était en grande partie liée à son agrégation et sa dégradation par les 2 voies protéasomale et lysosomale. 2) Nous avons analysé les mutations du gène F8 responsables de l’hémophilie A dans une large cohorte de patients. Leur analyse bio-informatique a permis de démontrer leur caractère délétère pour le FVIII. L’influence de ces mutations sur la survenue d’allo-anticorps anti-FVIII a été étudiée et stratifiée, en association avec l’origine ethnique et la recherche d’antécédents familiaux d’nticorps. 3) La recherche des facteurs influençant les taux de FVIII chez les conductrices d’hémophilie A a mis en évidence des déterminants majeurs : l’existence d’une maladie génétique additionnelle responsable d’un déficit en FVIII, le taux de facteur Willebrand et l’inactivation non aléatoire du chromosome X ; et des déterminants secondaires : l’âge, la sévérité de l’hémophilie, le polymorphisme D1241E du gène F8 et 5 nouveaux polymorphismes de la LRP1 localisés dans ses sites de liaison pour le FVIII. 4) Nous avons analysé 8 FVIII recombinant mutés in vitro en alanine dans la région 1808-1818 du FVIII. Les études antérieures n’analysant que la chaîne légère, ont montré que cette région était la plus affine pour le FIXa. Nous démontrons ici que la région 1808-1818 ne paraît pas si essentielle à la fonction du FVIIIcar au sein de la molécule entière, son affinité diminue et ses mutations n’altèrent que très modérément l’activité du FVIII. / The factor VIII (FVIII) is a glucoprotein of the coagulation, being the cofactor of the activated factor IX (FIXa). Its metabolism depends on various limiting factors or enhancing its survey or function. The objective of this research’s work was to analyse different parameters that could influence the plasma FVIII level and its pro-coagulant function. It included 4 parts : 1) We showed that the known intra-cellular retention of FVIII was mainly due to its aggregation and degradation following both proteasomal and lysosomal pathways. 2) We analysed FVIII gene mutations responsible for hemophilia A in a large patients cohort. The bio-informatic analysis demonstrated its deleterious consequence. The influence of these mutations on the anti-FVIII antibodies occurrence was stratified, in association with ethnicity and familial antecedent of inhibitor. 3) The research of factors influencing FVIII levels in hemophilia A carriers showed : i) major determinants such as the presence of an additional genetic disease characterised by a FVIII deficiency, the factor Willebrad’s level and the non-random inactivation of the X chromosome; and ii) minor determinants : age, severity of hemophilia, the polymorphism D1241E of FVIII gene, and 5 new polymorphisms of LRP1 located in its binding site for FVIII.4) We analysed 8 recombinant FVIII with in vitro created mutations in its 1808-1818 region. Previous studies that analysed only the FVIII light chain, have shown that this region constituted the more affine binding site of FVIII for FIXa. We demonstrated here that the 1808-1818 region is not as essential as it was reported because within the entire molecule, its affinity decreases and mutations affecting it do alter mildly the FVIII activity.

INTRODUÇÃO: Os Potenciais Evocados Auditivos avaliam a atividade neuroelétrica da via auditiva desde o nervo auditivo até o córtex cerebral. A vectoeletronistagmografia permite analisar os canais semicirculares e/ou nervo vestibular inferior, verificando se existe comprometimento vestibular periférico ou central. A reabilitação vestibular é composta de exercícios físicos ativos e repetitivos de olhos, cabeça e corpo e/ou manobras específicas que visam diminuir a tontura e a instabilidade corporal, aumentar a estabilização no olhar, o controle postural e melhorar o bem-estar na realização das atividades do diaa- dia. Levando-se em conta a escassez de trabalhos na literatura que investiguem a via auditiva central em indivíduos com síndrome vestibular periférica e que sejam submetidos à reabilitação vestibular, torna-se importante conhecer o funcionamento do sistema auditivo central, desde o tronco encefálico até o córtex auditivo, em indivíduos com vestibulopatias periféricas. OBJETIVOS: caracterizar os potenciais evocados auditivos de curta, média e longa latências em indivíduos com vestibulopatias periféricas, bem como verificar a evolução destes potenciais e dos resultados obtidos no Dizziness Handicap Inventory (DHI) frente à reabilitação vestibular. MÉTODOS: Foram submetidos à avaliação eletrofisiológica da audição por meio dos potenciais evocados auditivos de tronco encefálico (PEATE), potencial evocado auditivo de média latência (PEAML) e potencial cognitivo (P300), bem como à aplicação do questionário DHI, antes e após reabilitação vestibular, 20 indivíduos com diagnóstico de Síndrome Vestibular Periférica Irritativa (SVPI) e 17 indivíduos com diagnóstico de Síndrome Vestibular Periférica Deficitária (SVPD), com idades entre 20 e 70 anos. RESULTADOS: Os resultados demonstraram que o grupo com SVPD apresentou maior porcentagem de resultados alterados no PEATE e PEAML. No que diz respeito aos tipos de alterações, pode-se observar no grupo com SVPD, alteração em tronco encefálico baixo no PEATE pré e pós RV; aumento das latências das ondas Na e Pa no PEAML pós RV, aumento da latência da onda Pa pré RV e efeito eletrodo para a amplitude Na- Pa pós RV. No grupo com SVPI, foi observada alteração do tipo outros no PEATE pré RV; aumento da latência da onda Pa no PEAML pré e pós RV e ambas as alterações para a amplitude Na-Pa pós RV. No estudo da evolução dos resultados pré e pós RV, pode-se observar maior porcentagem de resultados semelhantes para os três potenciais, em ambos os grupos avaliados. Na comparação do DHI pré e pós RV, ocorreram melhores resultados para os aspectos físico, emocional e funcional no grupo com SVPI e para os aspectos físico e emocional no grupo com SVPD. Tornam-se necessários mais estudos que avaliem a via auditiva central destes indivíduos para uma melhor caracterização dos achados eletrofisiológicos / INTRODUCTION: The auditory evoked potentials assess the neuroelectrical activity of the auditory pathway from the auditory nerve to the cerebral cortex. The vectoelectronystagmography analyzes the semicircular canals and/or inferior vestibular nerve, checking peripheral or central vestibular involvement. The vestibular rehabilitation therapy consists in active exercises and repetitive eyes exercises, head and body and/or specific maneuvers to reduce the dizziness and body instability, increase gaze stability and postural control and also improve well-being in daily activities. Taking into account the scarcity of studies in the literature that investigate the central auditory pathways in subjects who underwent vestibular rehabilitation therapy, it becames important to know the central auditory system from the brainstem to the auditory cortex, in subjects with peripheral vestibular disorders. OBJECTIVE: To characterize the auditory evoked potentials of short, middle and long latencies in subjects with peripheral vestibular disorders, as well as to evaluate the development of these potentials and the results obtained in the Dizziness Handicap Inventory (DHI) after vestibular rehabilitation therapy (VRT). METHODS: brainstem auditory evoked potential (BAEP), Auditory Middle- Latency Response (AMLR), cognitive potential (P300) and DHI were carried out in 20 subjects with Peripheral Vestibular Hyperfunction Syndrome and 17 subjects with Peripheral Vestibular Hypofunction Syndrome, aged between 20 and 70, before and after vestibular rehabilitation therapy. RESULTS: The results showed that the Peripheral Vestibular Hypofunction Syndrome group, presented higher percentage of altered results on BAEP and AMLR. Comparing the normal and altered results (qualitative analysis) between the groups in the BAEP, lower brainstem was predominantly observed in the Peripheral Vestibular Hypofunction Syndrome group before and after VRT; increased latencies of Na and Pa waves in AMLR after VRT, incresead latency of Pa wave in AMLR before VRT and electrode effect to the Na-Pa amplitude after VRT. The alteration predominantly observed in the Peripheral Vestibular Hyperfunction Syndrome group, was the other type one before VRT; increased latency of Pa wave in AMLR before and after VRT and both changes to the Na-Pa amplitude after VRT. In the study of the evolution before and after VRT, it was observed a higher percentage of similar results for the three potentials in both groups. Comparing results before and after VRT, the DHI greatest improvement occurred for the physical, emotional and functional aspects in the Peripheral Vestibular Hyperfunction Syndrome group and for the physical and emotional aspects in the Peripheral Vestibular Hypofunction Syndrome group. Further studies that evaluate the central auditory pathway of individuals with peripheral vestibular syndrome are needed to better characterize the electrophysiological findings

Para investigar se estresse oxidativo contribui para a progressão da calcificação/estenose valvar aórtica (VA), avaliamos a produção de espécies reativas de oxigênio (ERO) e efeitos dos antioxidantes tempol e ác. lipóico em modelo de calcificação VA em coelhos. Superóxido, H2O2 e 3-nitrotirosina aumentaram em células inflamatórias e principalmente nos núcleos de calcificação, juntamente com as subunidades p22phox, Nox2 da NADPH oxidase e da proteína dissulfeto isomerase, que co-localizam. PCR mostrou aumento da Nox4 em relação a Nox1. A calcificação foi menor com ác.lipóico e maior com tempol, coicidindo com resultados de modelo in vitro em células musculares lisas. VA humanas estenóticas tiveram aumento semelhante de ERO e da expressão protéica em torno da calcificação. Estresse oxidativo pode contribuir para a progressão da estenose aórtica. / To invetigate whether oxidative stress contributes to aortic valve (AV) calcification/stenosis progression, we assessed reactive oxygen species (ROS) production and effects of antioxidants tempol and lipoic acid in a rabbit AV calcification model. Superoxide, H2O2 and 3-nitrotyrosine increased in inflammatory cells and mainly in calcifying nuclei, coincident with NADPH oxidase subunits p22phox, Nox2 and protein disulfide isomerase, which co-localized. PCR showed switch from Nox1 to Nox4. Calcification was smaller with lipoic acid and greater with tempol, similar to an in vitro smooth muscle cell calcification model results. Human stenotic AV had analogous increase in ROS and protein expression around calcifying nuclei. Oxidative stress can contribute to AV stenosis progression.

Objetivos A variação da pressão sistólica (VPS) é parâmetro de avaliação hemodinâmica em indivíduos ventilados mecanicamente. O objetivo deste estudo foi investigá-la em coelhos submetidos à hemorragia e pneumoperitônio. Método Estudou-se 11 coelhas sob 4 tratamentos: após 20 minutos de estabilização (T1); pneumoperitônio de 10mmHg por 30 minutos (T2); hemorragia de 20% da volemia estimada, realizada em 10 minutos, mais 10 minutos de estabilização, na vigência de pneumoperitônio (T3); após reposição do sangue retirado, em 10 minutos, mais 10 minutos de estabilização, sem pneumoperitônio (T4). Resultados Observou-se aumento de VPS significativo (p < 0,05) em T2 e T3, com maior valor em T3, em relação a T1 e que não houve diferença significativa entre T4 e T1. Delta Down tem maior participação na VPS nos tratamentos T1, T3 e T4. Em T2 a contribuição de ambas é equilibrada. Conclusões VPS mostrou ser preditora de hipovolemia durante hemorragia e pneumoperitônio / Systolic pressure variation (SPV) is a hemodynamic analysis parameter for mechanically ventilated individuals. The aim of this study was to investigate it in rabbits submitted to hemorrhage and pneumoperitoneum. Methods Eleven rabbits were studied under 4 treatments: after 20 minutes of stabilization (T1); 10 mmHg pneumoperitoneum for 30 minutes (T2); hemorrhage of 20% of the estimated volemia, performed in 10 minutes, followed by 10 minutes of stabilization, under pneumoperitoneum (T3); re-infusion in 10 minutes of the blood shed and more 10 minutes of stabilization, without pneumoperitoneum (T4). Results There was a significant increase in SPV (p < 0.05) in T2 and T3, with a higher value in T3, related to T1 and no difference between T4 and T1. Delta Down is the main component in T1, T3 and T4, while in T2 it is balanced with Delta Up. Conclusions SPV showed to be predictor of hypovolemia during hemorrhage and pneumoperitoneum