Simulation of stent deployment in a realistic human coronary artery

Background  

The process of restenosis after a stenting procedure is related to local biomechanical environment. Arterial wall stresses caused by the interaction of the stent with the vascular wall and possibly stress induced stent strut fracture are two important parameters. The knowledge of these parameters after stent deployment in a patient derived 3D reconstruction of a diseased coronary artery might give insights in the understanding of the process of restenosis.     

Proteomic Analysis of the Systemic Response to Radiographic Contrast Media

Introduction  

Radiographic contrast media (RCM) have numerous effects on the hemostatic system, inflammatory pathways, and vascular endothelium. Given the increasing number of high-risk patients undergoing radiographic procedures, more information regarding the systemic effects of RCM is needed.     

Alterations in regional vascular geometry produced by theoretical stent implantation influence distributions of wall shear stress: analysis of a curved coronary artery using 3D computational fluid dynamics modeling

Background  

The success of stent implantation in the restoration of blood flow through areas of vascular narrowing is limited by restenosis. Several recent studies have suggested that the local geometric environment created by a deployed stent may influence regional blood flow characteristics and alter distributions of wall shear stress (WSS) after implantation, thereby rendering specific areas of the vessel wall more susceptible to neointimal hyperplasia and restenosis. Stents are most frequently implanted in curved vessels such as the coronary arteries, but most computational studies examining blood flow patterns through stented vessels conducted to date use linear, cylindrical geometric models. It appears highly probable that restenosis occurring after stent implantation in curved arteries also occurs as a consequence of changes in fluid dynamics that are established immediately after stent implantation.     

Proteome profiling of embryo chick retina

Background  

Little is known regarding the molecular pathways that underlie the process of retinal development. The purpose of this study was to identify proteins which may be involved in development of retina. We used a proteomics-based approach to identify proteins that are up- or down-regulated during the development of the embryo chick retina.     

Axial stent strut angle influences wall shear stress after stent implantation: analysis using 3D computational fluid dynamics models of stent foreshortening

Introduction  

The success of vascular stents in the restoration of blood flow is limited by restenosis. Recent data generated from computational fluid dynamics (CFD) models suggest that the vascular geometry created by an implanted stent causes local alterations in wall shear stress (WSS) that are associated with neointimal hyperplasia (NH). Foreshortening is a potential limitation of stent design that may affect stent performance and the rate of restenosis. The angle created between axially aligned stent struts and the principal direction of blood flow varies with the degree to which the stent foreshortens after implantation.     

Computation of elementary modes: a unifying framework and the new binary approach

Background  

Metabolic pathway analysis has been recognized as a central approach to the structural analysis of metabolic networks. The concept of elementary (flux) modes provides a rigorous formalism to describe and assess pathways and has proven to be valuable for many applications. However, computing elementary modes is a hard computational task. In recent years we assisted in a multiplication of algorithms dedicated to it. We require a summarizing point of view and a continued improvement of the current methods.     

Phylophenetic properties of metabolic pathway topologies as revealed by global analysis

Background  

As phenotypic features derived from heritable characters, the topologies of metabolic pathways contain both phylogenetic and phenetic components. In the post-genomic era, it is possible to measure the "phylophenetic" contents of different pathways topologies from a global perspective.     

Non-viral eNOS gene delivery and transfection with stents for the treatment of restenosis

Background  

In this study, we have examined local non-viral gene delivery, transfection, and therapeutic efficacy of endothelial nitric oxide synthase (eNOS) encoding plasmid DNA administered using coated stents in a rabbit iliac artery restenosis model.     

Multicellular Tumour Spheroid as a model for evaluation of [18F]FDG as biomarker for breast cancer treatment monitoring

Background  

Pluripotent mouse embryonic stem (ES) cells can be induced in vitro to become neural progenitors. Upon transplantation, neural progenitors migrate toward areas of damage and inflammation in the CNS. We tested whether undifferentiated and neuralized mouse ES cells migrate toward media conditioned by glioma cell lines (C6, U87 & N1321) or Stem Cell Factor (SCF).     

Use of data mining techniques to investigate disease risk classification as a proxy for compromised biosecurity of cattle herds in Wales

Background  

Boar taint is the unpleasant odour and flavour of the meat of uncastrated male pigs that is primarily caused by high levels of androstenone and skatole in adipose tissue. Androstenone is a steroid and its levels are mainly genetically determined. Studies on androstenone metabolism have, however, focused on a limited number of genes. Identification of additional genes influencing levels of androstenone may facilitate implementation of marker assisted breeding practices. In this study, microarrays were used to identify differentially expressed genes and pathways related to androstenone metabolism in the liver from boars with extreme levels of androstenone in adipose tissue.     

Identification of androgen-coregulated protein networks from the microsomes of human prostate cancer cells

Background  

Androgens play a critical role in the development of prostate cancer-dysregulation of androgen-regulated growth pathways can led to hormone-refractory prostate cancer. A comprehensive understanding of androgen-regulated cellular processes has not been achieved to date. To this end, we have applied a large-scale proteomic approach to define cellular processes that are responsive to androgen treatment in LNCaP prostate cancer cells.     

MitoRes: a resource of nuclear-encoded mitochondrial genes and their products in Metazoa

Background  

Mitochondria are sub-cellular organelles that have a central role in energy production and in other metabolic pathways of all eukaryotic respiring cells. In the last few years, with more and more genomes being sequenced, a huge amount of data has been generated providing an unprecedented opportunity to use the comparative analysis approach in studies of evolution and functional genomics with the aim of shedding light on molecular mechanisms regulating mitochondrial biogenesis and metabolism.     

Computer aided analysis of additional chromosome aberrations in Philadelphia chromosome positive acute lymphoblastic leukaemia using a simplified computer readable cytogenetic notation

Background  

The analysis of complex cytogenetic databases of distinct leukaemia entities may help to detect rare recurring chromosome aberrations, minimal common regions of gains and losses, and also hot spots of genomic rearrangements. The patterns of the karyotype alterations may provide insights into the genetic pathways of disease progression.     

Small RNA sequencing reveals miR-642a-3p as a novel adipocyte-specific microRNA and miR-30 as a key regulator of human adipogenesis

Background  

In severe obesity, as well as in normal development, the growth of adipose tissue is the result of an increase in adipocyte size and numbers, which is underlain by the stimulation of adipogenic differentiation of precursor cells. A better knowledge of the pathways that regulate adipogenesis is therefore essential for an improved understanding of adipose tissue expansion. As microRNAs (miRNAs) have a critical role in many differentiation processes, our study aimed to identify the role of miRNA-mediated gene silencing in the regulation of adipogenic differentiation.     

Genome increase as a clock for the origin and evolution of life

Background  

The size of non-redundant functional genome can be an indicator of biological complexity of living organisms. Several positive feedback mechanisms including gene cooperation and duplication with subsequent specialization may result in the exponential growth of biological complexity in macro-evolution.     

Involvement of CD147 in overexpression of MMP-2 and MMP-9 and enhancement of invasive potential of PMA-differentiated THP-1

Background  

During infection and inflammation, circulating blood monocytes migrate from the intravascular compartments to the extravascular compartments, where they mature into tissue macrophages. The maturation process prepares the cells to actively participate in the inflammatory and immune responses, and many factors have been reported to be involved in the process. We found in our study that CD147 played a very important role in this process.     

Association of health behaviour with heart rate variability: a population-based study

Background

Multiple randomized controlled trials (RCTs) have examined the cardiovascular effects of omega-3 fatty acids and have provided unexplained conflicting results. A meta-analysis of these RCTs to estimate efficacy and safety and potential sources of heterogeneity may be helpful.

Methods

The Cochrane library, MEDLINE, and EMBASE were systematically searched to identify all interventional trials of omega-3 fatty acids compared to placebo or usual diet in high-risk cardiovascular patients. The primary outcome was all-cause mortality and secondary outcomes were coronary restenosis following percutaneous coronary intervention and safety. Meta-analyses were carried out using Bayesian random-effects models, and heterogeneity was examined using meta-regression.

Results

A total of 29 RCTs (n = 35,144) met our inclusion criteria, with 25 reporting mortality and 14 reporting restenosis. Omega-3 fatty acids were not associated with a statistically significant decreased mortality (relative risk [RR] = 0.88, 95% Credible Interval [CrI] = 0.64, 1.03) or with restenosis prevention (RR = 0.89, 95% CrI = 0.72, 1.06), though the probability of some benefit remains high (0.93 and 0.90, respectively). However in meta-regressions, there was a >90% probability that larger studies and those with longer follow-up were associated with smaller benefits. No serious safety issues were identified.

Conclusions

Although not reaching conventional statistical significance, the evidence to date suggests that omega-3 fatty acids may result in a modest reduction in mortality and restenosis. However, caution must be exercised in interpreting these benefits as results were attenuated in higher quality studies, suggesting that bias may be at least partially responsible. Additional high quality studies are required to clarify the role of omega-3 fatty acid supplementation for the secondary prevention of cardiovascular disease.     

The stochastic behavior of a molecular switching circuit with feedback

Background  

Using a statistical physics approach, we study the stochastic switching behavior of a model circuit of multisite phosphorylation and dephosphorylation with feedback. The circuit consists of a kinase and phosphatase acting on multiple sites of a substrate that, contingent on its modification state, catalyzes its own phosphorylation and, in a symmetric scenario, dephosphorylation. The symmetric case is viewed as a cartoon of conflicting feedback that could result from antagonistic pathways impinging on the state of a shared component.     

Fluvastatin in the therapy of acute coronary syndrome: Rationale and design of a multicenter, randomized, double-blind, placebo-controlled trial (The FACS Trial)[ISRCTN81331696]

Background

Stent length serves as a predictor of restenosis in use of bare metal stents (BMS). This has been demonstrated in a feasibility study that used a single short BMS implant (<9 mm) in a high proportion of lesions; the study observed a low rate of restenosis.

Methods

We performed a pilot prospective study to investigate in a series of consecutive patients the immediate and long-term effects of implantation of either 1) a single short BMS for all lesions with low probability of restenosis or 2) a drug-eluting stent (DES) for all other lesions.

Results

The 200 patients studied had 236 coronary artery lesions that were treated with short BMS in 168/236 patients (71.2%) and with DES in 68/236 patients (28.8%). Angiographic success was achieved in 230/236 lesions (97.5%) and procedural success in 194/200 patients (97.0%). Restenosis occurred in 15/153 lesions (9.8%) after short BMS, in 3/62 lesions (4.8%) after DES, and in 18/215 of all lesions (8.4%) angiographically controlled after six to eight months. Target vessel revascularization was performed in 16/218 lesion (7.4%).

Conclusion

Most of the coronary artery lesions in this small group of consecutive patients were treated sufficiently with a single BMS implant. This differential approach of treating suitable lesions in medium- to large-sized vessels with a single short BMS device and treating all other lesions with a DES implant resulted in a low incidence of restenosis.