Efeito da vitamina E na formaçao neo-intimal pós-angioplastia em modelo experimental com coelhos hipercolesterolemicos

Orientador : Alvaro Vieira MouraDissertaçao (mestrado) - Universidade Federal do Paraná, Setor de Ciencias da SaúdeResumo: Com o objetivo de avaliar o efeito da vitamina E (acetato de DL-a tocoferol) na proliferação intimai pós-angioplastia, foi desenvolvido um experimento com dezesseis coelhos submetidos à dieta hipercolesterolêmica a 1%. Os dezesseis coelhos foram divididos em dois grupos de oito animais. O primeiro grupo, chamado de Grupo A, foi alimentado com dieta aterogênica a 1% de colesterol, associada a 30mg/kg/dia de vitamina E, administrada diariamente. O segundo grupo (grupo controle), chamado de Grupo B, foi somente alimentado com dieta aterogênica a 1% de colesterol. Todos os animais permaneceram submetidos a suas respectivas dietas durante os trinta e seis dias em que durou o experimento. No décimo quinto dia, todos os animais foram sujeitados ao procedimento de criação das lesões na artéria central de suas orelhas. Este procedimento constituiu-se de uma compressão externa sobre a artéria central durante trinta minutos. Foram provocadas quatro lesões em cada animal: duas (proximal e distai) em cada orelha. Após 21 dias do procedimento, colheram-se amostras de sangue para a dosagem dos níveis de colesterol sérico, triglicerídeos, HDL e LDL e os coelhos foram sacrificados com dose letal de anestésico. As lesões arteriais foram avaliadas usando-se planimetria digital dos cortes histológicos. Os resultados obtidos mostraram elevação dos níveis de colesterol total, de triglicerídeos, da HDL e da LDL nos dois grupos, sem diferença estatística. Os resultados da análise morfométrica das lesões demostraram uma média de neo-íntima de 24,15% (em relação a camada média) no grupo tratado com vitamina E e de uma média de neo-íntima de 25,14% (em relação à camada média) no grupo controle, sem diferença estatisticamente significativa (p=0,587). Concluiu-se que a vitamina E (actetato de DL-a tocoferol na dose de 30mg/kg/dia) não modificou a formação neo-intimal pós-angioplastia neste modelo experimental.Abstract: This experiment was started to evaluate the effect of vitamin E (DL cxtocoferol acetate) on the neointimal proliferative response in rabbits fed with a hipercholesterolemic diet (cholesterol 1%). The rabbits were divided in two groups of eight. Both groups were fed with the antherogenic diet for 36 days. The first group (group A) was fed daily with the diet associated with vitamin E in a dosage of 30mg/Kg/day. The second group (group B) was fed only with the atherogenic diet. After 15 days all animals were submitted to the external compression or their ear's central arteries for thirty minutes in order to create the lesions. We produced four lesions in each animal, two in each ear (proximal and distal). After 21 days blood samples were taken to measure cholesterol, triglicerids, HDL and LDL. After that, the animals were sacrificed with a lethal dose of anesthesic. The histological cuts of the lesions were evaluated by digital planimetry. The results showed no statistical difference concerning the serical levels of cholesterol, triglicerids, HDL and LDL between groups. The morphometric analysis of the lesions showed no statistical difference of the mean values of neointimal proliferation between groups (group A=24,15% and group B=25,14%, P=0,587%). We concluded that vitamin E (DL a-tocoferol acetate), in a dosage of 30mg/Kg/day, did not modify the neointimal proliferative response using this experimental model

Time- and frequency-resolved fluorescence with a single TCSPC detector via a Fourier-transform approach

We introduce a broadband single-pixel spectro-temporal fluorescence detector, combining time-correlated single photon counting (TCSPC) with Fourier transform (FT) spectroscopy. A birefringent common-path interferometer (CPI) generates two time-delayed replicas of the sample’s fluorescence. Via FT of their interference signal at the detector, we obtain a two-dimensional map of the fluorescence as a function of detection wavelength and emission time, with high temporal and spectral resolution. Our instrument is remarkably simple, as it only requires the addition of a CPI to a standard single-pixel TCSPC system, and it shows a readily adjustable spectral resolution with inherently broad bandwidth coverag

Time- and frequency-resolved fluorescence with a single TCSPC detector via a Fourier-transform approach

We introduce a broadband single-pixel spectro-temporal fluorescence detector, combining time-correlated single photon counting (TCSPC) with Fourier transform (FT) spectroscopy. A birefringent common-path interferometer (CPI) generates two time-delayed replicas of the sample's fluorescence. Via FT of their interference signal at the detector, we obtain a two-dimensional map of the fluorescence as a function of detection wavelength and emission time, with high temporal and spectral resolution. Our instrument is remarkably simple, as it only requires the addition of a CPI to a standard single-pixel TCSPC system, and it shows a readily adjustable spectral resolution with inherently broad bandwidth coverage

Excitation-emission Fourier-transform spectroscopy based on a birefringent interferometer

The correlation of molecular excitation and emission events provides a powerful multidimensional spectroscopy tool, by relating transitions from electronic ground and excited states through two-dimensional excitation-emission maps. Here we present a compact, fast and versatile Fourier-transform spectrometer, combining absorption and excitation-emission fluorescence spectroscopy in the visible. We generate phase-locked excitation pulse pairs via an inherently stable birefringent wedge-based common-path interferometer, retaining all the advantages of Fourier-transform spectroscopy but avoiding active stabilization or auxiliary tracking beams. We employ both coherent and incoherent excitation sources on dye molecules in solution, with data acquisition times in the range of seconds and minutes, respectively

Safety of the Deferral of Coronary Revascularization on the Basis of Instantaneous Wave-Free Ratio and Fractional Flow Reserve Measurements in Stable Coronary Artery Disease and Acute Coronary Syndromes

OBJECTIVES The aim of this study was to investigate the clinical outcomes of patients deferred from coronary revascularization on the basis of instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR) measurements in stable angina pectoris (SAP) and acute coronary syndromes (ACS). BACKGROUND Assessment of coronary stenosis severity with pressure guidewires is recommended to determine the need for myocardial revascularization. METHODS The safety of deferral of coronary revascularization in the pooled per-protocol population (n = 4,486) of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation) and iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome) randomized clinical trials was investigated. Patients were stratified according to revascularization decision making on the basis of iFR or FFR and to clinical presentation (SAP or ACS). The primary endpoint was major adverse cardiac events (MACE), defined as the composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization at 1 year. RESULTS Coronary revascularization was deferred in 2,130 patients. Deferral was performed in 1,117 patients (50%) in the iFR group and 1,013 patients (45%) in the FFR group (p <0.01). At 1 year, the MACE rate in the deferred population was similar between the iFR and FFR groups (4.12% vs. 4.05%; fully adjusted hazard ratio: 1.13; 95% confidence interval: 0.72 to 1.79; p = 0.60). A clinical presentation with ACS was associated with a higher MACE rate compared with SAP in deferred patients (5.91% vs. 3.64% in ACS and SAP, respectively; fully adjusted hazard ratio: 0.61 in favor of SAP; 95% confidence interval: 0.38 to 0.99; p = 0.04). CONCLUSIONS Overall, deferral of revascularization is equally safe with both iFR and FFR, with a low MACE rate of about 4%. Lesions were more frequently deferred when iFR was used to assess physiological significance. In deferred patients presenting with ACS, the event rate was significantly increased compared with SAP at 1 year. (C) 2018 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.Peer reviewe

Efeito da vitamina E na formaçao neo-intimal pós-angioplastia em modelo experimental com coelhos hipercolesterolemicos

Orientador : Alvaro Vieira MouraDissertaçao (mestrado) - Universidade Federal do Paraná, Setor de Ciencias da SaúdeResumo: Com o objetivo de avaliar o efeito da vitamina E (acetato de DL-a tocoferol) na proliferação intimai pós-angioplastia, foi desenvolvido um experimento com dezesseis coelhos submetidos à dieta hipercolesterolêmica a 1%. Os dezesseis coelhos foram divididos em dois grupos de oito animais. O primeiro grupo, chamado de Grupo A, foi alimentado com dieta aterogênica a 1% de colesterol, associada a 30mg/kg/dia de vitamina E, administrada diariamente. O segundo grupo (grupo controle), chamado de Grupo B, foi somente alimentado com dieta aterogênica a 1% de colesterol. Todos os animais permaneceram submetidos a suas respectivas dietas durante os trinta e seis dias em que durou o experimento. No décimo quinto dia, todos os animais foram sujeitados ao procedimento de criação das lesões na artéria central de suas orelhas. Este procedimento constituiu-se de uma compressão externa sobre a artéria central durante trinta minutos. Foram provocadas quatro lesões em cada animal: duas (proximal e distai) em cada orelha. Após 21 dias do procedimento, colheram-se amostras de sangue para a dosagem dos níveis de colesterol sérico, triglicerídeos, HDL e LDL e os coelhos foram sacrificados com dose letal de anestésico. As lesões arteriais foram avaliadas usando-se planimetria digital dos cortes histológicos. Os resultados obtidos mostraram elevação dos níveis de colesterol total, de triglicerídeos, da HDL e da LDL nos dois grupos, sem diferença estatística. Os resultados da análise morfométrica das lesões demostraram uma média de neo-íntima de 24,15% (em relação a camada média) no grupo tratado com vitamina E e de uma média de neo-íntima de 25,14% (em relação à camada média) no grupo controle, sem diferença estatisticamente significativa (p=0,587). Concluiu-se que a vitamina E (actetato de DL-a tocoferol na dose de 30mg/kg/dia) não modificou a formação neo-intimal pós-angioplastia neste modelo experimental.Abstract: This experiment was started to evaluate the effect of vitamin E (DL cxtocoferol acetate) on the neointimal proliferative response in rabbits fed with a hipercholesterolemic diet (cholesterol 1%). The rabbits were divided in two groups of eight. Both groups were fed with the antherogenic diet for 36 days. The first group (group A) was fed daily with the diet associated with vitamin E in a dosage of 30mg/Kg/day. The second group (group B) was fed only with the atherogenic diet. After 15 days all animals were submitted to the external compression or their ear's central arteries for thirty minutes in order to create the lesions. We produced four lesions in each animal, two in each ear (proximal and distal). After 21 days blood samples were taken to measure cholesterol, triglicerids, HDL and LDL. After that, the animals were sacrificed with a lethal dose of anesthesic. The histological cuts of the lesions were evaluated by digital planimetry. The results showed no statistical difference concerning the serical levels of cholesterol, triglicerids, HDL and LDL between groups. The morphometric analysis of the lesions showed no statistical difference of the mean values of neointimal proliferation between groups (group A=24,15% and group B=25,14%, P=0,587%). We concluded that vitamin E (DL a-tocoferol acetate), in a dosage of 30mg/Kg/day, did not modify the neointimal proliferative response using this experimental model

Time-domain photocurrent spectroscopy based on a common-path birefringent interferometer

We present diffraction-limited photocurrent (PC) microscopy in the visible spectral range based on broadband excitation and an inherently phase-stable common-path interferometer. The excellent path-length stability guarantees high accuracy without the need for active feedback or post-processing of the interferograms. We illustrate the capabilities of the setup by recording PC spectra of a bulk GaAs device and compare the results to optical transmission data

Single-molecule excitation-emission spectroscopy

Single-molecule spectroscopy (SMS) provides a detailed view of individual emitter properties and local environments without having to resort to ensemble averaging. While the last several decades have seen substantial refinement of SMS techniques, recording excitation spectra of single emitters still poses a significant challenge. Here we address this problem by demonstrating simultaneous collection of fluorescence emission and excitation spectra using a compact common-path interferometer and broadband excitation, which is implemented as an extension of a standard SMS microscope. We demonstrate the technique by simultaneously collecting room-temperature excitation and emission spectra of individual terrylene diimide molecules and donor-acceptor dyads embedded in polystyrene. We analyze the resulting spectral parameters in terms of optical lineshape theory to obtain detailed information on the interactions of the emitters with their nanoscopic environment. This analysis finally reveals that environmental fluctuations between the donor and acceptor in the dyads are not correlated

Alterações histopatológicas associadas à braquiterapia intra-arterial com o samário-153

A lesão da parede arterial provocada por balão de angioplastia ou implante de próteses endovasculares em modelos experimentais e humanos pode provocar a reestenose do vaso, principalmente por migração e proliferação de células musculares lisas e síntese de matriz extracelular. Vários estudos demonstraram que a braquiterapia intra-arterial atua nestes fatores e, conseqüentemente, no tratamento da reestenose coronariana. Este estudo tem por objetivo avaliar as alterações vasculares morfológicas e morfométricas induzidas pela braquiterapia com samário-153 (153Sm), utilizando uma dose considerada ideal e outra elevada em coelhos hipercolesterolêmicos. Foram analisados 43 coelhos hipercolesterolêmicos e um total de 86 artérias ilíacas submetidas à lesão por balão de angioplastia, divididos em três grupos, sendo irradiados com as doses de 15Gy (n = 14) e 60Gy (n = 36) e controle (n = 36). Foram realizadas análise morfométrica (área neo-intimal, área da camada média, área do vaso) e análise histológica qualitativa para avaliação tecidual. O colesterol médio foi de 1.362 ± 497mg/dl nos três grupos. O achado mais relevante foi uma significativa inibição da hiperplasia neo-intimal no grupo irradiado com a dose de 15Gy, maior do que o controle e com a dose de 60Gy. Na dose de 60 Gy, além de ineficaz para inibir a proliferação neo-intimal, teve características tissulares e estruturais sugestivas de radiolesão, como presença de células xantomatosas, tecidos hialino e amorfo, proliferação vascular. Estas células, bem como o aumento das dimensões morfométricas do vaso, foram proporcionais aos graus de lesão nas lâminas elásticas interna e externa, sendo observados principalmente com a dose de 60Gy. Os segmentos médios das artérias ilíacas, representando o local de maior contato com o balão, tiveram maiores alterações morfométricas e celulares em relação aos segmentos referenciais (proximal e distal) nos três grupos. Em conclusão, o grupo de artérias submetidas à irradiação de 15Gy foi eficaz para a inibição da proliferação neo-intimal. O grupo irradiado com a maior dose de 60Gy foi ineficaz para inibir a hiperplasia neo-intimal e apresentou características morfométricas e teciduais compatíveis com a radiolesão vascular