RESUMO
The research into the pathophysiology of atherosclerosis has considerably increased our understanding of the disease complexity, but still many questions remain unanswered, both mechanistically and pharmacologically. Here, we provided evidence that the pro-oxidant enzyme Prenylcysteine Oxidase 1 (PCYOX1), in the human atherosclerotic lesions, is both synthesized locally and transported within the subintimal space by proatherogenic lipoproteins accumulating in the arterial wall during atherogenesis. Further, Pcyox1 deficiency in Apoe-/- mice retards atheroprogression, is associated with decreased features of lesion vulnerability and lower levels of lipid peroxidation, reduces plasma lipid levels and inflammation. PCYOX1 silencing in vitro affects the cellular proteome by influencing multiple functions related to inflammation, oxidative stress, and platelet adhesion. Collectively, these findings identify the pro-oxidant enzyme PCYOX1 as an emerging player in atherogenesis and, therefore, understanding the biology and mechanisms of all functions of this unique enzyme is likely to provide additional therapeutic opportunities in addressing atherosclerosis.
Assuntos
Aterosclerose/genética , Liases de Carbono-Enxofre/genética , Adulto , Idoso , Animais , Aterosclerose/metabolismo , Liases de Carbono-Enxofre/metabolismo , Feminino , Humanos , Inflamação/genética , Masculino , Camundongos , Pessoa de Meia-Idade , Estresse Oxidativo/genética , Adesividade Plaquetária/genéticaRESUMO
Realistic numerical models of human subjects and their surrounding environment represent the basic points of radiofrequency (RF) electromagnetic dosimetry. This also involves differentiating the human models in men and women, possibly with different body shapes and postures. In this context, the aims of this paper are, firstly, to propose a female dielectric anatomical model (fDAM) and, secondly, to compare the power absorption distributions of a male and a female model from 0.1 to 4 GHz. For realizing the fDAM, a magnetic resonance imaging tomographer to acquire images and a recent technique which avoids the discrete segmentation of body tissues into different types have been used. Simulations have been performed with the FDTD method by using a novel filtering-based subgridding algorithm. The latter is applied here for the first time to dosimetry, allowing an abrupt mesh refinement by a factor of up to 7. The results show that the whole-body-averaged specific absorption rate (WBA-SAR) of the female model is higher than that of the male counterpart, mainly because of a thicker subcutaneous fat layer. In contrast, the maximum averaged SAR over 1 g (1gA-SAR) and 10 g (10gA-SAR) does not depend on gender, because it occurs in regions where no subcutaneous fat layer is present.
Assuntos
Ondas de Rádio , Radiometria/métodos , Absorção , Tecido Adiposo/patologia , Adulto , Algoritmos , Peso Corporal , Feminino , Cabeça , Humanos , Imageamento por Ressonância Magnética , Masculino , Modelos Anatômicos , Modelos Teóricos , Imagens de Fantasmas , Postura , Doses de Radiação , Fatores SexuaisRESUMO
Complex permittivity values have a dominant role in the overall consideration of interaction between radiofrequency electromagnetic fields and living matter, and in related applications such as electromagnetic dosimetry. There are still some concerns about the accuracy of published data and about their variability due to the heterogeneous nature of biological tissues. The aim of this study is to provide an alternative semi-automatic method by which numerical dielectric human models for dosimetric studies can be obtained. Magnetic resonance imaging (MRI) tomography was used to acquire images. A new technique was employed to correct nonuniformities in the images and frequency-dependent transfer functions to correlate image intensity with complex permittivity were used. The proposed method provides frequency-dependent models in which permittivity and conductivity vary with continuity--even in the same tissue--reflecting the intrinsic realistic spatial dispersion of such parameters. The human model is tested with an FDTD (finite difference time domain) algorithm at different frequencies; the results of layer-averaged and whole-body-averaged SAR (specific absorption rate) are compared with published work, and reasonable agreement has been found. Due to the short time needed to obtain a whole body model, this semi-automatic method may be suitable for efficient study of various conditions that can determine large differences in the SAR distribution, such as body shape, posture, fat-to-muscle ratio, height and weight.
Assuntos
Algoritmos , Antropometria/métodos , Impedância Elétrica , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Modelos Anatômicos , Modelos Biológicos , Contagem Corporal Total/métodos , Carga Corporal (Radioterapia) , Simulação por Computador , Humanos , Imageamento por Ressonância Magnética/instrumentação , Micro-Ondas , Imagens de Fantasmas , Doses de Radiação , Radiometria/métodos , Raphanus , Eficiência Biológica Relativa , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Numerical human models for electromagnetic dosimetry are commonly obtained by segmentation of CT or MRI images and complex permittivity values are ascribed to each issue according to literature values. The aim of this study is to provide an alternative semi-automatic method by which non-segmented images, obtained by a MRI tomographer, can be automatically related to the complex permittivity values through two frequency dependent transfer functions. In this way permittivity and conductivity vary with continuity--even in the same tissue--reflecting the intrinsic realistic spatial dispersion of such parameters. A female human model impinged by a plane wave is tested using finite-difference time-domain algorithm and the results of the total body and layer-averaged specific absorption rate are reported.