Lipid-rich Plaques Detected by Near-infrared Spectroscopy Are More Frequently Exposed to High Shear Stress

High wall shear stress (WSS) and near-infrared spectroscopy (NIRS) detected lipid-rich plaque (LRP) are both known to be associated with plaque destabilization and future adverse cardiovascular events. However, knowledge of spatial co-localization of LRP and high WSS is lacking. This study investigated the co-localization of LRP based on NIRS and high WSS. Fifty-three patients presenting acute coronary syndrome underwent NIRS-intravascular-ultrasound (NIRS-IVUS) imaging of a non-culprit coronary artery. WSS was obtained using WSS profiling in 3D-reconstructions of the coronary arteries based on fusion of IVUS-segmented lumen and CT-derived 3D-centerline. Thirty-eight vessels were available for final analysis and divided into 0.5 mm/45° sectors. LRP sectors, as identified by NIRS, were more often colocalized with high WSS than sectors without LRP. Moreover, there was a dose-dependent relationship between lipid content and high WSS exposure. This study is a first step in understanding the evolution of LRPs to vulnerable plaques. [Figure not available: see fulltext.

Identification of a sheath-associated protein involved in phosphate transport in Sphaerotilus natans

Sphaerotilus natans was shown to have a fourfold lower K′ m of phosphate transport when grown in medium containing 0.1 m m phosphate, compared to cells grown in 10.0 m m phosphate. Analysis of sheath proteins from cells grown at these two phosphate levels revealed a protein of 53 kDa present in the sheath of cells grown at a phosphate concentration of 0.1 m m . This sheath-associated, phosphate-regulated protein, designated SapP, was gel purified and used to raise a polyclonal antibody. Enzyme-linked immunosorbent assay was used to localize this protein to the surface of the sheathed cells. Phosphate uptake assays done in the presence of the antibody also showed a rise in the K′ m of phosphate transport in cells grown in 0.1 m m phosphate, indicating that this protein is involved in high-affinity phosphate transport.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46762/1/253_2004_Article_BF00166797.pd

Bentall Procedure: A Systematic Review and Meta-Analysis

Background. The Bentall procedure is considered the gold standard in the treatment of patients requiring aortic root replacement. An up-to-date overview of outcomes after the Bentall procedure is lacking. Methods. We conducted a systematic review and meta-analysis of characteristics of and long-term outcome after the Bentall procedure with a mechanical valve prosthesis. Pooling was performed using the inverse variance method within a random-effects model. Outcome events are reported as linearized occurrence rates (percentage per patient year) with 95% confidence intervals. Results. In total, 46 studies with 7,629 patients (mean age, 50 years; 76% men) were selected. Pooled early mortality was 6% (422 patients). During a mean follow-up of 6 years (49,175 patient-years), the annual linearized occurrence rate for late mortality was 2.02% (1.77%-2.31%; 892 patients), for aortic root reoperation it was 0.46% (0.36%-0.59%), for hemorrhage it was 0.64% (0.47%-0.87%), for thromboemboli it was 0.77% (0.60%-1.00%), for endocarditis it was 0.39% (0.33%-0.46%), and for major adverse valve-related events it was 2.66% (2.17%-3.24%). Operations performed in more recent years were associated with lower rates of aortic root reoperation (beta = -0.452; p = 0.015). Conclusions. This systematic review illustrates that rates of aortic root reoperation after the Bentall procedure have decreased over the years. However, late mortality, major bleeding, and thromboembolic complications remain a concern. This report may be used to benchmark the potential therapeutic benefit of novel surgical approaches, such as valve-sparing aortic root replacement. (C) 2016 by The Society of Thoracic Surgeon

Vascular biomechanics and molecular disease activity in the thoracic aorta: a novel imaging method

Aims The influence haemodynamics have on vessel wall pathobiology in aortic disease is incomplete. This aim of this study was to develop a repeatable method for assessing the relationship between aortic wall shear stress (WSS) and disease activity by fusing 4D flow cardiovascular magnetic resonance (CMR) with hybrid positron emission tomography (PET). Methods and results As part of an ongoing clinical trial, patients with bicuspid aortic valve (BAV) were prospectively imaged with both 18F-sodium fluoride (18F-NaF) PET, a marker of calcification activity, and 4D flow CMR. We developed novel software allowing accurate 3D co-registration and high-resolution comparison of aortic peak systolic WSS and 18F-NaF PET uptake (maximum tissue-to-background ratio). Intra-observer repeatability of both measurements was determined using Bland–Altman plots and intra-class correlation coefficients (ICCs). The relationship between localized WSS and 18F-NaF uptake was analysed using linear mixed-effect models. Twenty-three patients with BAV (median age 50 [44–55] years, 22% female) were included. Intra-observer repeatability for WSS (ICC = 0.92) and 18F-NaF (ICC = 0.91) measurements obtained within 1.4 ± 0.6 cm2 regions of interest was excellent. On multivariable analysis, 18F-NaF PET uptake was independently and negatively associated with WSS as well as diastolic blood pressure (both P < 0.05), adjusted for age. Conclusion Fused assessment of WSS and 18F-NaF PET uptake is feasible and repeatable, demonstrating a clear association between these two factors. This high spatial resolution approach has major potential to advance our understanding of the relationship between vascular haemodynamics and disease activity

An MRI-based method to register patient-specific wall shear stress data to histology.

Wall shear stress (WSS), the frictional force exerted on endothelial cells by blood flow, is hypothesised to influence atherosclerotic plaque growth and composition. We developed a methodology for image registration of MR and histology images of advanced human carotid plaques and corresponding WSS data, obtained by MRI and computational fluid dynamics. The image registration method requires four types of input images, in vivo MRI, ex vivo MRI, photographs of transversally sectioned plaque tissue and histology images. These images are transformed to a shared 3D image domain by applying a combination of rigid and non-rigid registration algorithms. Transformation matrices obtained from registration of these images are used to transform subject-specific WSS data to the shared 3D image domain as well. WSS values originating from the 3D WSS map are visualised in 2D on the corresponding lumen locations in the histological sections and divided into eight radial segments. In each radial segment, the correlation between WSS values and plaque composition based on histological parameters can be assessed. The registration method was successfully applied to two carotid endarterectomy specimens. The resulting matched contours from the imaging modalities had Hausdorff distances between 0.57 and 0.70 mm, which is in the order of magnitude of the in vivo MRI resolution. We simulated the effect of a mismatch in the rigid registration of imaging modalities on WSS results by relocating the WSS data with respect to the stack of histology images. A 0.6 mm relocation altered the mean WSS values projected on radial bins on average by 0.59 Pa, compared to the output of original registration. This mismatch of one image slice did not change the correlation between WSS and plaque thickness. In conclusion, we created a method to investigate correlations between WSS and plaque composition

A química medicinal na próxima década Brazilian medicinal chemistry in the next decade

<abstract language="eng">Medicinal chemistry is multi, trans and inter disciplinary on its essence. It has a great deal of challenging Brazilian chemists in the next decade. The pharmacy school is essentially attached and has an important role in the development on the field that is still in domain of big pharmaceutical industries. This work shows the challenges to face and directions to jointly follow for a myriad of researchers throughout the country. The unnamed science has to work out through specific objectives in order to diminish the problems associated with human being health. A brief history is presented where the main goal is to devise chemistry, as a natural science, and many other interfaced disciplines