O objetivo deste estudo foi investigar os efeitos do hipotiroidismo experimental sobre o leito vascular da aorta torácica. Para a análise histológica foram realizadas colorações de hematoxilina-eosina, picrosirius e Weigert. Na análise de expressão proteica, foram realizadas as quantificações para colágeno I e III, elastina, MMP-9 e MMP-2, TIMP-1 e TIMP-2. As análises histológicas demonstraram uma diminuição da AST das aortas dos animais hipo e juntamente a esta alteração, foi constatada a diminuição da expressão proteica de colágeno do tipo I. Em relação à elastina, foi possível observar aumento da expressão deste elemento nas aortas dos animais hipotiroideos. Na avaliação da expressão proteica para MMP-9, foi possível verificar uma redução desta proteína no grupo hipotiroideo, assim como um aumento da expressão de TIMP-2. Frente aos presentes resultados, é possível sugerir que o estado hipometabólico desencadeado pelo hipotiroidismo afeta as CMLVs comprometendo mecanismos de síntese/degradação, alterando o importante arranjo da MEC presente na aorta torácica. / The aim of this study was to investigate hypothyroidism effects on thoracic aorta wall. For histological analyses were performed stains like hematoxilin-eosin, picrosirius and Weigert. In the protein expression assays were performed quantification for collagen I and III, elastin, MMP-9, MMP-2, TIMP-1 and TIMP-2. The histological analyses showed a decrease in aortas CSA and also a decrease in protein expression of collagen I in the hypo group. As regards to elastin, was possible to see an increase of this protein expression in hypo animals. In the evaluation for MMP-9 expression, was found a decrease in this protein and for TIMP-2 an increase in hypothyroidism group. Facing to these results, is possible to suggest that the hypometabolic state triggered by hypothyroidism, affects the VSMCs compromising mechanisms of synthesis/degradation and changing the important constitution of thoracic aorta ECM.

A cirurgia de revascularização do miocárdio (CRVM) é um procedimento indicado para pacientes com angina pectoris não controlada com o tratamento clínico e para pacientes com elevado grau de obstrução das artérias principais. A cirurgia visa a melhorar a qualidade de vida relacionada à saúde (QVRS) dos pacientes, aliviar os sintomas da angina e aumentar a sobrevida, sobretudo dos pacientes de maior risco. No contexto do paciente coronariopata, a depressão tem sido relacionada como um preditor de pior QVRS, enquanto o senso de coerência (SC) tem sido associado a melhor QVRS e menor depressão. Objetivos: Avaliar a QVRS, depressão e SC, antes e seis meses após a CRVM e investigar as associações entre essas variáveis. Casuística e método: Estudo observacional e prospectivo, realizado em um hospital-escola no interior do Estado de São Paulo, desenvolvido entre os meses de setembro de 2006 e abril de 2008. A amostra foi constituída por 54 pacientes que fizeram parte das duas avaliações. Foram utilizados três instrumentos de medida: para avaliação da QVRS, o Medical Outcomes Study 36 - item Short-Form (SF-36), para a depressão, o Inventário de Depressão de Beck (IDB) e para o SC, o Questionário de Senso de Coerência de Antonovsky de 29 itens (QSCA). Os dados foram coletados por meio de entrevistas. Posteriormente, foram sumarizados por meio de estatística descritiva e analisados pelo teste de correlação de Pearson e teste t. A análise de regressão hierárquica foi realizada para verificar as associações entre a depressão, seis meses após a cirurgia, o sexo, idade, depressão préoperatória e SC, as quais se mostraram estatisticamente significantes nas análises bivariadas. O nível de significância adotado foi 0,05. Resultados: Os participantes eram, predominantemente, do sexo masculino, casados e com baixo nível de escolaridade. As médias obtidas, nos oito domínios do SF-36, foram maiores na segunda avaliação, quando comparadas ao pré-operatório, sendo as diferenças estatisticamente significantes. A medida de depressão foi maior antes do que após cirurgia (p=0,01) e não houve alteração na medida do SC (p=0,51). No préoperatório, as mulheres apresentaram menor avaliação da QVRS nos componentes do SF-36, exceto para Aspectos emocionais (p=0,68). A idade apresentou correlação moderada e positiva com o Estado geral de saúde (r=0,342, p=0,01) e com o SC (r=314, p=0,02), enquanto que moderada e negativa com a medida de depressão (r= -0,307, p=0,02). Após seis meses, os homens apresentaram melhor avaliação em todos os componentes do SF-36, sendo essa diferença estatisticamente significativa para Aspectos físicos (p=0,04), Dor (p=0,02), Estado geral de saúde (p=0,01) e Vitalidade (p=0,04). A idade demonstrou correlação positiva e forte com Estado geral de saúde (r=570, p=0,00) e moderada com Saúde mental (r=0,388, p=0,00). Para testar se a presença de depressão, seis meses após a cirurgia, associava-se com a depressão existente no pré-operatório, bem como com as variáveis sexo e idade, foi realizada regressão linear hierárquica cujo resultado mostrou que 49% da variância da medida de depressão, seis meses após a cirurgia, era explicada por essas variáveis. Com a inclusão da medida de SC no modelo constatou-se que essa variável explicou sozinha 18,7% da variância da medida de depressão, após o ajuste das demais variáveis. Conclusão: A QVRS melhora seis meses após a CRVM, assim como há diminuição da depressão, enquanto o SC não apresentou alteração, confirmando a estabilidade do constructo. Após o ajuste no modelo de regressão para as variáveis: sexo, idade e depressão no pré-operatório, o SC explica 18,7% da depressão pós-operatória, resultado importante em se tratando de uma variável psicossocial. / The myocardial revascularization surgery (MRS) is a recommended procedure for patients who suffer from angina pectoris which is not controlled under clinical treatment and for patients who have an elevated degree of obstruction of the main coronary arteries. The surgery aims at improving patients health-related quality of life, alleviating the symptoms of the angina and increasing their survival period, particularly of those at greater risk. As to the coronaropathy in patients, depression has been related to a predictor for worse HRQL, whereas the sense of coherence (SC) has been associated with a better HRQL and lower depression. Objectives: To evaluate the HRQL, depression and SC before MRS and six months after it and to investigate the associations among these variables. Casuistics and method: A prospective and observational study, which was carried out at a hospital school in the countryside of the State of São Paulo and developed between September 2006 and April 2008. The sample was constituted of 54 patients who took part in the two evaluations. Three instruments of measurement were utilized: to evaluate HRQL, the Medical Outcomes Study 36 - item Short-Form (SF-36), towards depression, the Beck Depression Inventary (BDI) and regarding SC, the Questionnaire of Sense of Coherence by Antonovsky of 29 items (QSCA). The data were collected by means of interviews. Later, they were summarized through descriptive statistics and analysed by our using the test of correlation by Peterson and the t test. The analysis of hierarchical regression was carried out to verify the associations among the depression, six months after the surgery, sex, age, pre-operatory depression and SC, which were shown to be statistically significant in the bivariate analyses. The adopted level of significance was 0,05. Results: The participants were predominantly male, married and had a low level of instruction. The averages obtained, in the eight domains of SF-36, were higher in the second evaluation when compared to the preoperatory period, being such differences statistically significant. The measurement of depression was higher before than after the surgery (p=0,01) and there was no alteration in the measurement of SC (p=0,51). In the pre-operatory period, women presented a lower evaluation of HRQL in the components of SF-36, except towards Emotional aspects (p=0,68). Age presented moderate and positive correlation towards the General state of health (r=0,342, p=0,01) and with the SC (r=314, p=0,02), whereas a moderate and negative one regarding the measurement of depression (r= -0,307, p=0,02). After six months, men showed a better evaluation in all the components of SF-36, being such a difference statistically significant towards Physical aspects (p=0,04), Pain (p=0,02), General state of health (p=0,01) and Vitality (p=0,04). Age demonstrated to have a strong and positive correlation with the General state of health (r=570, p=0,00) and a moderate one with Mental health (r=0,388, p=0,00). To test if the presence of depression, six months after the surgery, was associated with the existent pre-operatory depression, as well as with the variables sex and age, hierarchical linear regression was carried out whose result revealed that 49% of the variance of the measurement of depression, six months after the surgery, was explained by such variables. With the inclusion of SC measurement in the model, it was stated that this variable explained 18,7% of the variance of the measurement of depression by itself, after the adjustment of the other variables. Conclusion: The HRQL improves after six months of the MRS, depression diminishes, whereas the SC did not show any alteration, confirming the stability of the construct. After the adjustment in the model of regression towards the variables: sex, age and depression in the pre-operatory period, SC explains 18,7% of postoperatory depression, an important result regarding it is a psychosocial variable.

Sabe-se que o sistema imune, através de um fenômeno denominado imunossenescência, gradativamente diminui a sua capacidade de resposta durante a vida. Este fato pode tornar o indivíduo mais suscetível a infecções e outras patologias. Neste contexto, seria útil procurar por fatores que alterassem esta evolução natural, principalmente os capazes de acelerar este processo. Por esta razão, nós procuramos por diferenças nos parâmetros imunológicos entre o antes e o depois da cirurgia de valva cardíaca em idosos com mais de 65 anos. Nossos resultados não apontaram, no pós-operatório, para uma diminuição da capacidade imune, uma vez que os testes cutâneos de hipersensibilidade para o PPD, tricofitina e candidina não se alteraram. Quando a resposta linfoproliferativa foi avaliada in vitro, também não apresentou diferença. Por outro lado, nós observamos um aumento na porcentagem de células T CD3 +, T CD4 + e monócitos no sangue periférico, quando comparamos os períodos. Sendo que os marcadores de ativação cellular CD25 +, CD69 + e o CD95 também se apresentaram elevados. Quanto a secreção de citocinas, nossos resultados apontam para um amento de IL-4 e IL-8. Inversamente, concentrações reduzidas de IL-2, IL-12 e IFN- foram detectadas no sobrenadante de PBMCs quando estimuladas in vitro. Em suma, nossos dados demonstram que a cirurgia de valva cardiaca é capaz de alterar vários parâmetros da resposta immune, com um aumenrto da porcentagem de células, quanto da expressão de marcadores de ativação celular e secreção de citocinas / It is known that the immune system, through a phenomenon called immunosenescence, undergoes functional changes during life which may culminate in a diminished capacity of response, turning the subject more susceptible to infections and other pathologies. In this context, it is useful to search for factors that alter this natural evolution, mainly able to delay this process. For this reason, we assessed different immunologic parameters before and after cardiac valve surgery in 65 year-old patients. Our results did not point to a postoperative immunedeficiency-like state, once that the cutaneous tests to PPD, candidin and tricophytin remained positive for most of the subjects. When the proliferative response was assessed in vitro, there were also no differences. On the other hand, we observed a post-surgical increase in the percentage of T CD3 +, T CD4 + cells and in monocytes from peripheral blood when we compare both periods. Moreover, it is important to highlight that activation markers, such as CD25, CD69 and CD95 were also presented in higher levels. According to the cytokine secretion, our results appointed to a greater secretion of IL-4 and IL-8 postoperative. Conversely, reduced concentrations of IL-2, IL-12 and IFN- were detected in supernatant of PBMCs when stimulated in vitro. In summary, our data reveal that the cardiac valve surgery with extra corporeal procedure and anesthesia is able to alter several parameters of the immune response, with an increased percentage of the major assessed cells, as well as in the expression of activation markers and cytokine secretion

BACKGROUND: It is well established that thoracic aortic aneurysms (TAA) and abdominal aortic aneurysms (AAA) have different risk factors, clinical features, and genetic influences. Differences between and amongst subtypes of TAAs have received less attention. Despite observations of divergent clinical outcomes between ascending thoracic aortic aneurysms (ATAAs) and descending thoracic aortic aneurysms (DTAAs), etiologic factors determining the anatomic distribution of these aneurysms are not well understood. METHODS: From 3,247 patients registered in an institutional Thoracic Aortic Center Database from July 1992 through August 2013, we identified 921 patients with full aortic dimensional imaging by CT or MRI scan with TAA > 3.5 cm and without evidence of aortic dissection (AoD). Patients were analyzed in three groups: isolated ATAA (n=677), isolated DTAA (n=97), and combined ATAA and DTAA (n=146). RESULTS: Patients with a DTAA, alone or with coexistent ATAA, had significantly more hypertension (80.6% vs. 61.8%, p<.001) and a higher burden of atherosclerotic disease ( 86.7% vs. 7.5%, p<.001) ) and were more likely to be female (59.3% vs. 29.5%, P<.001). Conversely, patients with isolated ATAA were significantly younger (average age 59.5 vs. 71, p<.001), and contained almost every case of overt genetically-triggered TAA. Patients with isolated DTAA were demographically indistinguishable from patients with combined ATAA and DTAA. In follow up, patients with isolated DTAA, or with ATAA and DTAA, experienced significantly more aortic events (aortic dissection/rupture) and had higher mortality than patients with isolated ATAA. CONCLUSIONS: Based on patient characteristics and outcomes, subtypes of TAA emerge. DTAA with or without associated ATAA or AAA appears to be a disease more highly associated with atherosclerosis, hypertension, and advanced age. In contrast, isolated ATAA appears to be a clinically distinct entity with a higher burden of genetically triggered disease. These data have important implications for familial screening recommendations for TAA.

Made available in DSpace on 2014-06-11T19:22:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-02-27Bitstream added on 2014-06-13T19:27:34Z : No. of bitstreams: 1 oliveira_gcv_me_botfm.pdf: 521554 bytes, checksum: 4e1594735e9b4ade8985592087d02570 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Foi realizado estudo experimental em cães para avaliar a eficácia da anestesia peridural torácica e seus efeitos na respiração, comparando-se dois volumes, 0,25 e 0,33 ml/kg do anestésico local ropivacaína a 0,75%. Para isso foram utilizados oito animais, sem raça definida, com idade entre um e três anos, com peso médio de 24,7 ± 6,3 Kg, em boas condições de saúde. Para isso foi necessária anestesia prévia dos animais a fim de se determinar a concentração anestésica mínima na qual o animal apresentasse resposta positiva a um estímulo elétrico. Sendo assim a indução foi realizada com isofluorano na concentração inicial de 5% no vaporizador calibrado, através de máscara facial e a intubação foi efetuada. O estímulo elétrico foi realizado com corrente de 50 V em 50 ciclos/s de 10 milisegundos. Se a resposta fosse negativa, a concentração era reduzida em 0,2%, sendo o procedimento repetido até que o animal apresentasse resposta positiva para a determinação do estímulo supra máximo positivo. Um cateter peridural foi introduzido do espaço lombossacro até a região torácica das vértebras T1-T2. Foi administrada ropivacaína e as avaliações foram realizadas por dois avaliadores que não tinham conhecimento do tratamento utilizado. Os parâmetros aferidos foram freqüência cardíaca, respiratória, pressões arteriais, ritmo cardíaco, concentração expirada de CO2, volume minuto, volume corrente, hemogasometria e temperatura esofágica. A avaliação do bloqueio sensitivo foi realizada através da avaliação do estímulo elétrico e de pinçamento da pele para avaliação do panículo nervoso. Houve redução da freqüência cardíaca e de pressão arterial, o que revela um bloqueio simpático com os dois grupos. Houve depressão respiratória, pois os dois grupos apresentaram elevação do CO2, e foram colocados sob ventilação controlada... / Experimental study was conducted in dogs to assess the effectiveness of the thoracic epidural anesthesia and their effects on respiration, compared two volumes, 0.25 and 0.33 ml / kg of local anesthetic ropivacaine at 0.75%. For that eight animals were used, mixed breed, aged between one and three years, with average weight of 24.7 ± 6.3 kg, in good health. For this was required anesthesia of the animals prior to find the minimum anesthesia concentration that the animal had a positive response to electrical stimulation. Thus the induction was performed with isoflurane in the initial concentration of 5% in precision vaporizer by face mask and intubation was performed. The electrical stimulation was performed with current of 50 V at 50 cycles / s, 10 milliseconds. If the purposeful gross movement was negative, the concentration was reduced by 0.2%, and the procedure repeated until the animal had a positive response for determining the maximum positive stimulus above. An epidural catheter was introduced into the space lombossacro to the region of thoracic vertebrae T1-T2. Ropivacaine was administered and the evaluations were conducted by two evaluators who were not aware of treatment used. The parameters were measured heart rate, breathing, blood pressure, heart rate, expired concentration of CO2, minute volume, tidal volume, blood gas and esophageal temperature. The assessment of sensory block was done through evaluation of electrical stimulation and clamping the skin to assess the panículous nervous. Decreased heart rate and blood pressure, which shows a sympathetic block with the two groups. There was respiratory depression, since both groups had elevation of CO2, and were placed under controlled ventilation, which prevented the evaluation of spontaneous ventilation. The pinch of the skin test showed a blockage in extensive loss of nerve panículous in two groups, with no statistical... (Complete abstract click electronic access below)

A Dissertation Submitted to the Faculty of Science University of the Witwatersrand, Johannesburg for the Degree of Master of Science January, 1990 / This is a study of the morphological and functional aspects of A. africanus thoracic and lumbar vertebrae in comparison with those of modern human and anthropoid ape vertebrae. The purpose is to determine if any derived features in the morphology of hominids, as distinct from primitive features shared with non-hominids, were present and if so to what stage of attainment of full erectness such features point. The major results of this study are as follows: (i) There is a difference in the configuration of the lumbar articular facets between pongids, on the one hand, and modern human and A. africanus, on the other hand. This difference suggests that similar stresses operate in these regions in the two hominid groups. (ii) Bony adaptation to a developed lumbar lordosis is present in A. africanus. (iii) Major agreement has been found in the relative dimensions of modern human and A. africanus lumbar vertebrae, in contrast to those of pongid vertebrae. This indicates probable correspondence in the pattern of weight transmission to the pelvis in modern humans and A. africanus. (iv) The decrease of inferior lumbar vertebral body area starts at higher levels in sts 14 (an A. africanus partial skeleton) than in modern man, suggesting a longer curved lower lumbar region in A. africanus. From these results it may be concluded that the trunk was probably carried in a fully erect posture in A. africanus. The bony adaptation thereto, however, may not have been fully developed as in modern man. It is proposed that, in Sts 14, the last two lumbar vertebrae were carried at an angle relative to each other and to the sacrum, in contrast to the abrupt change in direction between L5 and the sacrum in modern man.

Actin isoform specific mutations have been identified as causes for various human diseases. These include twelve missense mutations in γ-nonmuscle actin leading to early onset autosomal dominate nonsyndromic hearing loss and twenty two missense mutations in α-smooth muscle actin leading to thoracic aortic aneurysms and dissections (TAAD). The molecular mechanisms leading to these human pathologies are mainly unknown, principally due to the inability to isolate pure mutant γ-nonmuscle actin and α-smooth muscle actin in quantities required for biochemical analysis. To begin to address these problems, I have individually expressed the human nonmuscle actin isoforms, β– and γ– nonmuscle actin, in a baculovirus expression system and characterized their biochemical properties. Surprisingly, despite a conserved amino acid difference of only 4 residues at or near the N-terminus, Ca-γ-actin exhibits slower monomeric and filamentous biochemical properties than β-actin. In the Mg-form, the difference between the two is smaller. Mixing experiments with Ca-actins reveal the two will readily co-polymerize. Calcium bound in the high affinity binding site of γ-actin may cause a selective energy barrier relative to β-actin that retards the equilibration between G– and F-monomer conformations resulting in a slower polymerizing actin with greater filament stability. This difference may be particularly important in sites such as the γ-actin-rich cochlear hair cell stereocilium where local mM calcium concentrations may exist. In hair cells γ-nonmuscle actin seems to play a central role in stereocilia maintenance. To determine how the deafness causing D51N-γ-mutant actin mutation leads to deafness, I expressed and characterized it in the γ-actin background. The D51N mutation, lethal when cloned into yeast, displayed decreased filament stability and polymerization kinetics of an actin more dynamic than γ-actin. This result suggests that the hearing effects of the γ-actin mutations on the hearing apparatus are not simply caused by an inability to polymerize. The observed increased polymerization rates and decreased filament stability may have major implications for the human disease, as the mutation may alter the ability of the γ-actin to fulfill its maintenance functions. To address the basis by which TAAD mutations cause vascular dysfunction I introduced two of the know human mutations, N115T and R116Q, into yeast actin, 86% identical to human α-smooth muscle actin. I then generated yeast strains expressing each of these mutations as the sole actin in the cell to assess their effect on actin function in vivo and in vitro. Both mutant strains exhibited reduced ability to grow under a variety of stress conditions, although the N115T cells were more severely affected. In vitro the mutations caused exhibited altered thermostability and nucleotide exchange rates indicating effects on monomer conformation with R116Q the most severely affected. The N115T actin demonstrated a biphasic elongation phase during polymerization, while R116Q actin demonstrated a markedly extended nucleation phase. Allele-specific effects were also seen on critical concentration, rate of depolymerization and filament treadmilling. R116Q filaments were hypersensitive to severing by the actin-binding protein cofilin. In contrast, N115T filaments were hyposensitive to cofilin, despite near normal binding affinities of actin for cofilin. The mutant specific effects on actin behavior suggest that individual mechanisms may contribute to TAAD. Understanding the mechanisms of actin dependent human diseases requires elucidation of the effects of the mutations on the behavior of actin per se, its regulation, and the impact on actin mediated processes within the cell. The work provided in this thesis and future studies will provide the information required to understand the pathways involved in these diseases and form innovative treatments for deafness and TAAD.

Objective: Evaluation of surgical quality ensures consistency of care and facilitates improvements in the quality of care delivered. Methods: An overview of surgical quality measurement is presented. A system for monitoring thoracic morbidity and mortality (TM&M) at the Ottawa Hospital is introduced and evaluated. Results of a needs assessment survey on the involvement in thoracic surgical research and quality improvement initiatives are presented. Results: Structure, process, and outcomes reflect different viewpoints on how to evaluate surgical quality. The feasibility of the TM&M system is evaluated using descriptive and univariate statistics, while its inter-rater reliability is assessed amongst the Canadian Association of Thoracic Surgeons. Conclusions: Outcomes have been fundamental in the evaluation of surgical quality. TM&M classification system advocates for a practice of continuous quality improvement and provides standardized and reliable feedback on surgical outcomes. Results of the needs assessment have built a strong foundation of knowledge on prospective ways to enhance the monitoring of surgical quality.

No description available.

Objective: Evaluation of surgical quality ensures consistency of care and facilitates improvements in the quality of care delivered. Methods: An overview of surgical quality measurement is presented. A system for monitoring thoracic morbidity and mortality (TM&M) at the Ottawa Hospital is introduced and evaluated. Results of a needs assessment survey on the involvement in thoracic surgical research and quality improvement initiatives are presented. Results: Structure, process, and outcomes reflect different viewpoints on how to evaluate surgical quality. The feasibility of the TM&M system is evaluated using descriptive and univariate statistics, while its inter-rater reliability is assessed amongst the Canadian Association of Thoracic Surgeons. Conclusions: Outcomes have been fundamental in the evaluation of surgical quality. TM&M classification system advocates for a practice of continuous quality improvement and provides standardized and reliable feedback on surgical outcomes. Results of the needs assessment have built a strong foundation of knowledge on prospective ways to enhance the monitoring of surgical quality.