Narrowing Of Blood Vessels Research Articles

Large-Scale, Ion-Current-Based Proteomic Investigation of the Rat Striatal Proteome in a Model of Short- and Long-Term Cocaine Withdrawal.

Given the tremendous detriments of cocaine dependence, effective diagnosis and patient stratification are critical for successful intervention yet difficult to achieve due to the largely unknown molecular mechanisms involved. To obtain new insights into cocaine dependence and withdrawal, we employed a reproducible, reliable, and large-scale proteomics approach to investigate the striatal proteomes of rats (n = 40, 10 per group) subjected to chronic cocaine exposure, followed by either short- (WD1) or long- (WD22) term withdrawal. By implementing a surfactant-aided precipitation/on-pellet digestion procedure, a reproducible and sensitive nanoLC-Orbitrap MS analysis, and an optimized ion-current-based MS1 quantification pipeline, >2000 nonredundant proteins were quantified confidently without missing data in any replicate. Although cocaine was cleared from the body, 129/37 altered proteins were observed in WD1/WD22 that are implicated in several biological processes related closely to drug-induced neuroplasticity. Although many of these changes recapitulate the findings from independent studies reported over the last two decades, some novel insights were obtained and further validated by immunoassays. For example, significantly elevated striatal protein kinase C activity persisted over the 22 day cocaine withdrawal. Cofilin-1 activity was up-regulated in WD1 and down-regulated in WD22. These discoveries suggest potentially distinct structural plasticity after short- and long-term cocaine withdrawal. In addition, this study provides compelling evidence that blood vessel narrowing, a long-known effect of cocaine use, occurred after long-term but not short-term withdrawal. In summary, this work developed a well-optimized paradigm for ion-current-based quantitative proteomics in brain tissues and obtained novel insights into molecular alterations in the striatum following cocaine exposure and withdrawal.

Simulation of balloon angioplasty in residually stressed blood vessels—Application of a gradient-enhanced fibre damage model

In this contribution we study the balloon angioplasty in a residually stressed artery by means of a non-local gradient-enhanced fibre damage model. The balloon angioplasty is a common surgical intervention used to extend or reopen narrowed blood vessels in order to restore the continuous blood flow in, for instance, atherosclerotic arteries. Inelastic, i.e. predominantly damage-related and elastoplastic processes are induced in the artery during its inflation resulting in an irreversible deformation. As a beneficial consequence, provided that the inelastic deformations do not exceed a specific limit, higher deformations can be obtained within the same pressure level and a continuous blood flow can be guaranteed. In order to study the mechanical response of the artery in this scenario, we make use of the non-local gradient-enhanced model proposed in Waffenschmidt et al. (2014). In this contribution, we extend this model to make use of an incompressible format in connection with a Q1Q1P0 finite element implementation. The residual stresses in the artery are also taken into account following the framework presented in Waffenschmidt (2015). From the results it becomes apparent that, when the artery is subjected to radial stresses beyond the physiological range, damage evolution is triggered in the collagen fibres. The impact of the residual stresses on the structural response and on the circumferential stress distribution along the thickness of the arterial wall is also studied. It is observed that the residual stresses have a beneficial effect on the mechanical response of the arterial wall.

The effectiveness of essential fatty acid, B vitamin, Vitamin C, magnesium and zinc supplementation for managing stress in women: a systematic review protocol

The effectiveness of essential fatty acid, B vitamin, Vitamin C, magnesium and zinc supplementation for managing stress in women: a systematic review protocol

A simple method for establishing an ostrich model of femoral head osteonecrosis and collapse.

BackgroundThis study aimed to develop a simple method of creating an animal model of non-trauma femoral head osteonecrosis and collapse using African ostriches with weights similar to those of humans.MethodsEighteen African ostriches were subjected to liquid nitrogen cryo-insult in the unilateral femoral head through surgical procedures using homemade cryogenic equipment combined with tract drilling inside the femoral head. Three animals were sacrificed at postoperative weeks 6 and 12, respectively, and the remaining animals were sacrificed at postoperative week 24. Bilateral femoral heads were harvested and subjected to gross observation, histological examination using hematoxylin and eosin staining, and radiographic examination. Micro-computed tomography was performed on a portion of the specimens at postoperative week 24, and angiographic examination of the femoral head was performed before sacrificing the animals.ResultsEight ostriches developed a limp at postoperative week 8, with a mean duration of 16.5 weeks. The postoperative femoral head specimens showed changes in contour and articular cartilage degeneration. Sagittal sectioning of the collapsed femoral head specimens revealed distinct boundaries among the osteonecrotic areas, osteosclerotic areas, and normal trabeculae. Histological examinations revealed active bone resorption in the osteonecrotic area of the subchondral bone, an increased number of fat cells, and active trabecular bone regeneration in the osteosclerotic areas. The postoperative radiographic examinations revealed that the height of the femoral head gradually decreased and progressed to collapse. Micro-computed tomography scans showed the interrupted trabecular bone with an irregular shape in the collapsed femoral head. Compared with the normal samples, angiographic findings revealed interrupted blood supply of the cryo-injured samples in some areas of the femoral heads, blood vessel narrowing, and decreased number of blood vessels in the cryo-injured areas.ConclusionThis study indicates that an animal model of osteonecrotic femoral head progressing to collapse can be established via a simplified method of cryosurgery. This model possesses histological features that are similar to those of humans; thus, it can be used as an ideal animal model for the study of femoral head necrosis.

Opiate dependence and withdrawal: role of oxidative stress in opiate regulations

Abstract not availableBangladesh Journal of Medical Science Vol.14(2) 2015 p.215

Computational analysis of the radial mechanical performance of PLLA coronary artery stents

Stents have been an effective tool to restore and maintain the patency of narrowed blood vessels, but they must have sufficient radial strength. Biodegradable stent materials have substantially lower mechanical properties than permanent stents. The stent geometry and material properties must be considered simultaneously when assessing stent performance. Material tests were performed to determine the mechanical characteristics of high-molecular-weight poly-l-lactic acid (PLLA). The results were used to calibrate an anisotropic elastic-plastic material model. Three distinct geometries were analysed with a range of material stiffness values in a finite element analysis to investigate their comparative effect on the radial strength, recoil, and radial stiffness. The performance of the different geometries varies substantially, with one particular geometry, with the highest material stiffness of 9GPa, exceeding the desired radial strength of 300mmHg.

EFFECTS OF CHEMICAL REACTION AND THERMAL RADIATION ON MHD FLOW OVER AN INCLINED PERMEABLE STRETCHING SURFACE WITH NON-UNIFORM HEAT SOURCE/SINK: AN APPLICATION TO THE DYNAMICS OF BLOOD FLOW

An analysis is performed to study the unsteady hydromagnetic heat and mass transfer of blood in a time-dependent porous narrow blood vessel over a permeable inclined stretching surface under slip conditions. The unsteadiness in the flow, temperature and concentration fields is caused by the time dependence of the stretching velocity, surface temperature and the surface concentration. Thermal radiation, chemical reaction, velocity slip, thermal slip and concentration slips are considered. Similarity transformations are used to convert the governing time-dependent non-linear boundary layer equations for momentum, heat equation and species equations into a system of ordinary differential equations. The resulting non-linear coupled differential equations are solved numerically by using fourth order Runge–Kutta scheme together with shooting method. The influence of pertinent parameters on velocity, temperature, concentration, skin-friction coefficient, Nusselt number and Sherwood number has been studied and numerical results are presented graphically and in tabular form. Comparisons with previously published work are performed and the results are found to be in excellent agreement.

Modulation of vascular smooth muscle cell phenotype by STAT-1 and STAT-3

ObjectiveSmooth muscle cell (SMC) de-differentiation is a key step that leads to pathological narrowing of blood vessels. De-differentiation involves a reduction in the expression of the SMC contractile genes that are the hallmark of quiescent SMCs. While there is considerable evidence linking inflammation to vascular diseases, very little is known about the mechanisms by which inflammatory signals lead to SMC de-differentiation. Given that the Signal Transducers and Activators of Transcription (STAT) transcriptional factors are the key signaling molecules activated by many inflammatory cytokines and growth factors, the aim of the present study was to determine if STAT transcriptional factors play a role SMC de-differentiation. Methods and resultsUsing shRNA targeted to STAT-1 and STAT-3, we show by real time RT-PCR and Western immunoblots that STAT-1 significantly reduces SMC contractile gene expression. In contrast, STAT-3 promotes expression of SMC contractile genes. Over-expression studies of STAT-1 and STAT-3 confirmed our observation that STAT-1 down-regulates whereas STAT-3 promotes SMC contractile gene expression. Bioinformatics analysis shows that promoters of all SMC contractile genes contain STAT binding sites. Finally, using ChIP analysis, we show that both STAT-1 and STAT-3 associate with the calponin gene. ConclusionThese data indicate that the balance of STAT-1 and STAT-3 influences the differentiation status of SMCs. Increased levels of STAT-1 promote SMC de-differentiation, whereas high levels of STAT-3 drive SMC into a more mature phenotype. Thus, inhibition of STAT-1 may represent a novel target for therapeutic intervention in the control of vascular diseases such as atherosclerosis and restenosis.

Engineering micropatterned surfaces to modulate the function of vascular stem cells

Multipotent vascular stem cells have been implicated in vascular disease and in tissue remodeling post therapeutic intervention. Hyper-proliferation and calcified extracellular matrix deposition of VSC cause blood vessel narrowing and plaque hardening thereby increasing the risk of myocardial infarct. In this study, to optimize the surface design of vascular implants, we determined whether micropatterned polymer surfaces can modulate VSC differentiation and calcified matrix deposition. Undifferentiated rat VSC were cultured on microgrooved surfaces of varied groove widths, and on micropost surfaces. 10μm microgrooved surfaces elongated VSC and decreased cell proliferation. However, microgrooved surfaces did not attenuate calcified extracellular matrix deposition by VSC cultured in osteogenic media conditions. In contrast, VSC cultured on micropost surfaces assumed a dendritic morphology, were significantly less proliferative, and deposited minimal calcified extracellular matrix. These results have significant implications for optimizing the design of cardiovascular implant surfaces.

A Retrospective Survey Studying the Impact of Fabry Disease on Pregnancy.

Fabry disease (FD) is a lysosomal storage disorder resulting from a deficiency of lysosomal enzyme α-galactosidase A (α-gal A). Reduced or missing α-gal A enzyme results in the storage of globotriaosylceramide (GL3) and related glycosphingolipids in the cellular lysosomes throughout the body. The majority of GL3 buildup occurs in the body's vasculature resulting in narrowed blood vessels and an increased risk for strokes, transient ischemic attacks, and deep vein thrombosis. Theoretical concerns have been raised about increased pregnancy complications in women affected by FD as glycosphingolipid storage has been found in both maternal- and fetal-derived placental tissues. This retrospective study was conducted to better understand risks for women with FD during pregnancy. Survey questions included queries about prenatal medications, teratogenic exposures, prenatal testing, common pregnancy complications, Fabry symptoms during pregnancy, obstetrical history, and immediate neonatal history. In total, 41 affected women completed the survey. Results indicate several Fabry-related symptoms and features may worsen during pregnancy, including gastrointestinal symptoms, acroparesthesias, proteinuria, headaches, and postpartum depression. Although no life-threatening complications were reported, a statistically significant increased frequency of hypertension was observed when comparing data from this study to the general population (p < 0.05) and previous publications (p < 0.001). Limitations include sample size and recall bias. Though this survey sampling of women was small and required women to recall their past pregnancy experiences, the findings suggest that when pregnant, women with FD should be aware of potential worsening of FD symptoms and may benefit from consulting with a maternal-fetal medicine specialist.

Biomechanical Modeling of Human Finger

Many of the studies in the biomechanics of the human body made globally focused primarily on hand-arm. This segment of the human body is considered a "gateway" of vibrations to other parts of the body or to internal organs. A long-term exposure to these mechanical vibration (caused by vibrating hand equipment: drill, grinder, etc.) affects the soft tissues and may lead to a dangerous syndrome, that is particularly vibration white finger (VWF), which is narrowing of blood vessels, a phenomenon that in time and untreated can even cause gangrene. This article focuses on a dynamic model with three degrees of freedom of the human finger. Some dynamic characteristics, such as centre of gravity, stiffness and damping, using both a rigid body structure system and computer simulations can be determined after measuring the vibrations.

Understanding the mechanisms of sickle cell disease by simulations with a discrete particle model

Sickle cell disease (SCD) is an inherited blood disorder characterized by rigid, sickle-shaped red blood cells (RBCs). Because of their rigidity and shape, sickle cells can get stuck in smaller blood vessels, causing blockages and depriving oxygen to tissues. This study develops and applies mathematical models to better understand the mechanism of SCD. Two-dimensional models of RBCs and blood vessels have been constructed by representing them as discrete particles interacting with different forces. The nonlinear, elastic property of healthy RBCs could be adequately reproduced using a cosine angle bending force and a worm-like chain spring force. With the ability to deform, RBCs can squeeze through narrow blood vessels. In modeling sickle cells as rigid bodies and applying repelling and friction forces from the blood vessel, this study shows that geometrical factors (dimensions of the sickle cell and blood vessels) as well as rigidity and adhesiveness of the sickle cell all play an important role in determining how, and if, sickle cells become trapped within narrow blood capillaries. With lack of data to validate the model, this study primarily provides a sensitivity analysis of factors influencing sickle cell occlusion and identified critical data to support future modeling.

The frontiers of nuclear cardiology research

The frontiers of nuclear cardiology research

PET/SPECT imaging of hindlimb ischemia: focusing on angiogenesis and blood flow

Peripheral artery disease (PAD) is a result of the atherosclerotic narrowing of blood vessels to the extremities, and the subsequent tissue ischemia can lead to the up-regulation of angiogenic growth factors and formation of new vessels as a recovery mechanism. Such formation of new vessels can be evaluated with various non-invasive molecular imaging techniques, where serial images from the same subjects can be obtained to allow the documentation of disease progression and therapeutic response. The most commonly used animal model for preclinical studies of PAD is the murine hindlimb ischemia model, and a number of radiotracers have been investigated for positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging of PAD. In this review article, we summarize the PET/SPECT tracers that have been tested in the murine hindlimb ischemia model as well as those used clinically to assess the extremity blood flow.

Morphological features of coronary arteries and lesions in hearts from five species of sharks collected from the northwestern Atlantic Ocean

Morphological features of coronary arteries and incidental lesions are reported from hearts in five species of sharks, the shortfin mako shark, Isurus oxyrhinchus Rafinesque, thresher shark Alopias vulpinus (Bonaterre), blue shark, Prionace glauca L., the smooth dogfish, Mustelus canis (Mitchill), and spiny dogfish, Squalus acanthias L. Sharks were collected from the northwestern Atlantic between June and August from 1996 to 2010. They were necropsied dockside and the hearts were preserved in buffered formalin. Routine sections including ventricle/conus arteriosus and the atrio-ventricular junctions were embedded in paraffin, stained with common histological and immunohistochemical methods and examined by brightfield microscopy. Myointimal hyperplasia, medial myo-myxomatous hyperplasia and bifurcation pads were observed commonly, and medial muscle reorientation and epicardial myeloid tissues were rare. All the above features differed in severity, prevalence and distribution depending on anatomical site and shark species/size. Morphometric analysis indicated that myomyxomatous hyperplasia is associated with luminal narrowing of blood vessels. As suggested previously, the described morphological features are most likely physiological responses to blood flow characteristics. Vascular and cardiac lesions were uncommon and included, granulomatous proliferative epicarditis with fibroepitheliomas, myxomatous epicardial expansions, medial arterial vacuolation, myocardial fibrosis, acute ventricular emboli and parasitic granulomas. The lesions of embolism, proliferative and granulomatous epicarditis and myocardial fibrosis were in all sharks associated with capture events including retained fishing hooks. The significance and aetiopathogenesis of medial vacuolation and epicardial myxomatous expansions remains unclear.

Shear-Activated Nanotherapeutics for Drug Targeting to Obstructed Blood Vessels

Obstruction of critical blood vessels due to thrombosis or embolism is a leading cause of death worldwide. Here, we describe a biomimetic strategy that uses high shear stress caused by vascular narrowing as a targeting mechanism--in the same way platelets do--to deliver drugs to obstructed blood vessels. Microscale aggregates of nanoparticles were fabricated to break up into nanoscale components when exposed to abnormally high fluid shear stress. When coated with tissue plasminogen activator and administered intravenously in mice, these shear-activated nanotherapeutics induce rapid clot dissolution in a mesenteric injury model, restore normal flow dynamics, and increase survival in an otherwise fatal mouse pulmonary embolism model. This biophysical strategy for drug targeting, which lowers required doses and minimizes side effects while maximizing drug efficacy, offers a potential new approach for treatment of life-threatening diseases that result from acute vascular occlusion.

Fuzzy 기법을 이용한 관상동맥영상의 에지추출

Coronary Intervention treatment has become the core that is the test of cardiac catheterization to conduct treatment with Coronary Arteriography. Operators must be careful in Coronary Intervention treatment because the stent is inserted into the point of narrowing of blood vessel. So, the operator must correctly recognize the path of blood vessel to deal with the problems which are damages and ruptures of blood vessel, and there would be some errors of finding the path of blood vessel by bad qualify of the image. Therefore in this paper, median filtering is conducted by preprocessing to evaluate the performance of the effect of noise of the image that affects quality of the image and Fuzzy Edge Extraction Techniques is tested by using Soble Edge Extraction Techniques to compare the performance with The Fuzzy Edge Extraction Techniques. In result, the performance, removing the noise and extracting the signal of Fuzzy Edge Extraction Techniques using median filtering, demonstrates the superiority.

Targeted Biodegradable Nanoparticles for Drug Delivery to Smooth Muscle Cells

Targeted delivery of therapeutic agents to prevent smooth muscle cell (SMC) proliferation is important in averting restenosis (a narrowing of blood vessels). Since platelet derived growth factor (PDGF) receptors are over-expressed in proliferating SMCs after injury from cardiovascular interventions, such as angioplasty and stent implantation, our hypothesis is that conjugation of PDGF-BB (platelet-derived growth factor BB (homodimer)) peptides to biodegradable poly (D,L-lactic-co-glycolide) (PLGA) nanoparticles (NPs) would exhibit an increased uptake of these NPs by proliferating SMCs. In this study, poly (D,L-lactide-co-glycolide) (PLGA) nanoparticles containing dexamethasone were formulated and conjugated with PDGF-BB peptides. These NPs were stable, biocompatible, and exhibited a sustained drug release over 14 days. Various particle uptake studies using HASMCs (human aortic smooth muscle cells) demonstrated that PDGF-BB peptide-conjugated nanoparticles significantly increased cellular uptake and decreased proliferation of HASMCs compared to control nanoparticles (without conjugation of PDGF-BB peptides). These NPs were internalized primarily by clathrin-mediated endocytosis and macropinocytosis. Our in vitro results suggest that PDGF-BB peptide-conjugated NPs could represent as an effective targeted, sustained therapeutic delivery system to reduce restenosis and neointimal hyperplasia.

Elastomeric degradable biomaterials by photopolymerization-based CAD-CAM for vascular tissue engineering

A predominant portion of mortalities in industrial countries can be attributed to diseases of the cardiovascular system. In the last decades great efforts have been undertaken to develop materials for artificial vascular constructs. However, bio-inert materials like ePTFE or PET fail as material for narrow blood vessel replacements (coronary bypasses). Therefore, we aim to design new biocompatible materials to overcome this. In this paper we investigate the use of photoelastomers for artificial vascular constructs since they may be precisely structured by means of additive manufacturing technologies. Hence, 3D computer aided design and manufacturing technologies (CAD-CAM) offer the possibility of creating cellular structures within the grafts that might favour ingrowth of tissue. Different monomer formulations were screened concerning their suitability for this application but all had drawbacks, especially concerning the suture tear resistance. Therefore, we chose to modify the original network architecture by including dithiol chain transfer agents which effectively co-react with the acrylates and reduce crosslink density. A commercial urethane diacrylate was chosen as base monomer. In combination with reactive diluents and dithiols, the properties of the photopolymers could be tailored and degradability could be introduced. The optimized photoelastomers were in good mechanical accordance with native blood vessels, showed good biocompatibility in in vitro tests, degraded similar to poly(lactic acid) and were successfully manufactured with the 3D CAD-CAM technology.

Apelin induces enlarged and nonleaky blood vessels for functional recovery from ischemia

AbstractThe efficacy of therapeutic angiogenesis for revascularization in ischemia using genes, proteins, and cells has been established. For further improvement, processes allowing enlargement of the luminal cavity to facilitate efficient blood flow need to be facilitated. Recently, we found that expression of APJ and its specific ligand, apelin, is seen in endothelial cells when angiogenesis is taking place during embryogenesis. Apelin-deficient mice are viable but have narrow intersomitic vessels during embryogenesis and narrow blood vessels in the trachea and skin after birth. Apelin induces the formation of larger cords of endothelial cells, mainly mediated by cell-cell aggregation, resulting in the generation of larger blood vessels. Here we report that transgenic overexpression of apelin in keratinocytes induces enlarged but not leaky blood vessels in the dermis. In the hind limb ischemia model, apelin together with vascular endothelial growth factor (VEGF) effectively induced functional vessels larger than with VEGF alone. Endogenous apelin is required for the suppression of VEGF-, histamine-, or inflammation-induced vascular hyperpermeability. Apelin inhibited the down-modulation of vascular endothelial-cadherin by VEGF, resulting in suppression of hyperpermeability. Our results suggest apelin efficacy for therapeutic angiogenesis.