Tissue Vessels Research Articles

Angiopoietin/Tie2 Axis Regulates the Age-at-Injury Cerebrovascular Response to Traumatic Brain Injury.

Although age-at-injury influences chronic recovery from traumatic brain injury (TBI), the differential effects of age on early outcome remain understudied. Using a male murine model of moderate contusion injury, we investigated the underlying mechanism(s) regulating the distinct response between juvenile and adult TBI. We demonstrate similar biomechanical and physical properties of naive juvenile and adult brains. However, following controlled cortical impact (CCI), juvenile mice displayed reduced cortical lesion formation, cell death, and behavioral deficits at 4 and 14 d. Analysis of high-resolution laser Doppler imaging showed a similar loss of cerebral blood flow (CBF) in the ipsilateral cortex at 3 and 24 h post-CCI, whereas juvenile mice showed enhanced subsequent restoration at 2-4 d compared with adults. These findings correlated with reduced blood-brain barrier (BBB) disruption and increased perilesional vessel density. To address whether an age-dependent endothelial cell (EC) response affects vessel stability and tissue outcome, we magnetically isolated CD31+ ECs from sham and injured cortices and evaluated mRNA expression. Interestingly, we found increased transcripts for BBB stability-related genes and reduced expression of BBB-disrupting genes in juveniles compared with adults. These differences were concomitant with significant changes in miRNA-21-5p and miR-148a levels. Accompanying these findings was robust GFAP immunoreactivity, which was not resolved by day 35. Importantly, pharmacological inhibition of EC-specific Tie2 signaling abolished the juvenile protective effects. These findings shed new mechanistic light on the divergent effects that age plays on acute TBI outcome that are both spatial and temporal dependent.SIGNIFICANCE STATEMENT Although a clear "window of susceptibility" exists in the developing brain that could deter typical developmental trajectories if exposed to trauma, a number of preclinical models have demonstrated evidence of early recovery in younger patients. Our findings further demonstrate acute neuroprotection and improved restoration of cerebral blood flow in juvenile mice subjected to cortical contusion injury compared with adults. We also demonstrate a novel role for endothelial cell-specific Tie2 signaling in this age-related response, which is known to promote barrier stability, is heightened in the injured juvenile vasculature, and may be exploited for therapeutic interventions across the age spectrum following traumatic brain injury.

Coinhibition of mTORC1/mTORC2 and RhoA /ROCK pathways prevents chronic rejection of rat cardiac allografts

Chronic rejection of transplanted organs remains an unresolved issue in clinical organ transplantation. The macrophages play a crucial role in the development of chronic rejection. We showed previously that macrophage-specific deletion of RhoA or RhoA/ROCK inhibition prevent macrophage movement to the cardiac allografts and abrogate chronic rejection in rodent transplantation models. Here we assessed the ability of the mTORC1 and mTORC2 inhibitor everolimus, alone or in conjunction with the RhoA/ROCK inhibitor Y27632, to inhibit chronic rejection of Wistar Furth (WF; RT1.Au) rat cardiac allografts heterotopically transplanted into ACI (RT1.Aa) recipients. The transplanted hearts were analyzed for vessel occlusion and tissue fibrosis. T cell and macrophage subsets infiltration was analyzed by immunostaining with T cell and macrophage molecular markers. We found that a combination of the mTOR inhibitor everolimus and the RhoA/ROCK inhibitor Y27632 prolonged allograft survival; decreased vessel occlusion, collagen deposition, and macrophage infiltration; and inhibited the chronic rejection of rat cardiac allografts. These results indicate that coinhibition of the mTORC1/mTORC2 and RhoA pathways in transplant recipients abrogates chronic rejection of rat cardiac allografts, and will aid in the development of clinically applicable anti-chronic rejection therapies.

Fabrication of heterogeneous porous bilayered nanofibrous vascular grafts by two-step phase separation technique

Innterconnected porous architecture is critical for tissue engineering scaffold as well as biomimetic nanofibrous structure. In addition, a paradigm shift is recently taking place in the scaffold design from homogeneous porous scaffold to heterogeneous porous scaffold for the complex tissues. In this study, a versatile and simple one-pot method, dual phase separation, is developed to fabricate macroporous nanofibrous scaffold by phase separating the mixture solutions of immiscible polymer blends without using porogens. The macropores in the scaffold are interconnected, and their size can be tuned by the polymer blend ratio. Moreover, benefiting from the easy operation of dual phase separation technique, an innovative, versatile and facile two-step phase separation method is developed to fabricate heterogeneous porous layered nanofibrous scaffolds with different shapes, such as bilayered tubular scaffold and tri-layered cylindrical scaffold. The bilayered tubular nanofibrous scaffold composed of poly(l-lactic acid) (PLLA)/poly(l-lactide-co-ε-caprolactone) (PLCL) microporous inner layer and PLLA/poly(ε-caprolactone) (PCL) macroporous outer layer matches simultaneously the functional growth of endothelial cells (ECs) and smooth muscle cells (SMCs), and shows the favorable performance for potential small diameter blood vessel application. Therefore, this study provides the novel and facile strategies to fabricate macroporous nanofibrous scaffold and heterogeneous porous layered nanofibrous scaffold for tissue engineering applications. Statement of SignificanceThe fabrication of porous tissue engineering scaffold made of non-water-soluble polymer commonly requires the use of porogen materials. This is complex and time-consuming, resulting in greater difficulty to prepare heterogeneous porous layered scaffold for multifunctional tissues repair, such as blood vessel and osteochondral tissue. Herein, a novel, versatile and simple one-pot dual phase separation technique is developed for the first time to fabricate porous scaffold without using porogens. Simultaneously, it also endows the resultant scaffold with the biomimetic nanofibrous architecture. Based on the easy operation of this dual phase separation technique, a facile two-step phase separation method is also put forward for the first time and applied in fabricating heterogeneous porous layered nanofibrous scaffold for tissue engineering applications.

Neuroendocrine tumors of the small intestine causing a desmoplastic reaction of the mesentery are a more aggressive cohort

Desmoplastic reaction of the mesentery is commonly seen in patients with neuroendocrine tumors of the small intestine. However, it is not clear whether desmoplastic reaction is associated with tumor-specific characteristics and diminished prognosis. Therefore, the aim of this study was to investigate whether the presence of a desmoplastic reaction correlates with prognostic and molecular markers of neuroendocrine tumors of the small intestine. Patients with neuroendocrine tumors of the small intestine operated at our department from 2000 to 2016 were analyzed. Patient and tumor characteristics were evaluated. Kaplan-Meier and multivariate analyses were performed. In total, 148 patients underwent surgery, and preoperative imaging was available in 113 patients. A total of 45 patients showed desmoplastic reaction of the mesentery and progression-free survival was significantly impaired (26 months versus 65.4 months) compared with patients without desmoplastic reaction. These patients had significantly more often distant metastases (84.4% vs 39.7%), lymphatic vessel (68.9% vs 44.1%), and perineural tissue infiltration (57.8% vs 17.6%) compared with patients without desmoplastic reaction. However, proliferation index (positive desmoplastic reaction 4.1% versus negative desmoplastic reaction 3.3%) and tumor size (positive desmoplastic reaction 2 cm versus negative desmoplastic reaction 1.9 cm) were not diverging significantly. This study revealed that tumors leading to desmoplastic reaction are more aggressive, despite similar Ki67 indices.

What is the pathogenesis of proximal hypospadias?

To report the information concerning the pathogenesis of proximal hypospadias and causes of curvature associated with it. From January 2009 to December 2015, 74 patients underwent repair of proximal hypospadias. In 70 patients we performed a systematic biopsies in the lateral areas of the urethral plate, as well as under this plate. The study of the histological structure of these areas was performed using routine staining with hematoxylin and eosin, and the Masson's trichrome which color the collagen fibers in blue and monoclonal antibody against alpha-smooth muscle actin. This prospective study shows that the fibrotic tissue abnormally present on the ventral side of the penis consists of a mixture of fibrous connective tissue, nerve nets, short vessels, and smooth muscle fibers. In contrast to the scrotal dartos, penile dartos fascia does not contain smooth muscle fibers. Therefore, these fibers may come from a blood vessel or spongy tissue which existed during neonatal period in the distal part of the penis before disappearing. In addition, in 13 cases, the presence downstream of the urethral meatus, of a bifurcation of corpus spongiosum into two branches supposes that the corpus spongiosum is form by fusion around the urethra of two mesenchymal bodies. The arterial supply of this purely masculine formation originates from a new vascularization and it is probably, developed under secretion of androgens (angiogenic substances in target tissues). These findings allow us to suggest that the proximal hypospadias is due to avascular necrosis of the distal part ie. poorly vascularized part of the corpus spongiosum.

Regulation of von-Willebrand Factor Secretion from Endothelial Cells by the Annexin A2-S100A10 Complex.

Endothelial cells serve as gatekeepers of vascular hemostasis and local inflammatory reactions. They can rapidly respond to changes in the environment, caused, for example, by blood vessel injury, tissue damage or infection, by secreting in a strictly regulated manner factors regulating these processes. These factors include adhesion receptors for circulating leukocytes and platelets, P-selectin and von-Willebrand factor (VWF) that are stored in specialized secretory granules of endothelial cells, the Weibel-Palade bodies (WPB). Acute exposure of these adhesion molecules converts the endothelial cell surface from an anti-adhesive state enabling unrestricted flow of circulating blood cells to an adhesive one capable of capturing leukocytes (through P-selectin) and platelets (through VWF). While these are important (patho)physiological responses, compromised or dysregulated WPB secretion can cause pathologies such as excessive bleeding or vascular occlusion. Several factors are involved in regulating the exocytosis of WPB and thus represent potential targets for therapeutic interventions in these pathologies. Among them, the annexin A2 (AnxA2)-S100A10 complex has been shown to participate in the tethering/docking of secretion-competent WPB at the plasma membrane, and interference with AnxA2/S100A10 expression or complex formation significantly reduces acute WPB exocytosis and VWF release. Thus, developing specific means to efficiently block AnxA2-S100A10 complex formation in endothelial cells could lead to novel avenues towards interfering with acute vascular thrombosis.

Screening RhoA/ROCK inhibitors for the ability to prevent chronic rejection of mouse cardiac allografts

BackgroundChronic rejection of transplanted organs is a major obstacle in organ transplantation. The main symptoms of chronic rejection are vessel occlusion and tissue fibrosis. Macrophages play a crucial role in chronic rejection. We showed previously that RhoA deletion or RhoA/Rock inhibition using Y27632 inhibitor reorganizes macrophage actin cytoskeleton, prevents macrophage movement to the cardiac allografts, and abrogates chronic rejection in rodent models. Although besides Y27632 there are other RhoA/ROCK inhibitors available commercially, their efficacy in inhibition of chronic rejection remains unknown. MethodsWe screened four RhoA/Rock inhibitors for their ability to inhibit chronic rejection of BALB/c [H-2d] mouse cardiac allografts heterotopically transplanted into C57BL/6 [H-2b] recipients. We also tested the effect of inhibitors on macrophages in vitro. ResultsWe found that out of four tested compounds, the Fasudil and Azaindole, inhibited vessel occlusion, tissue fibrosis, decreased M2 macrophage infiltration and abrogated chronic rejection of mouse cardiac allografts. The remaining inhibitors, SAR-407899 and SLX-2119, decreased only tissue fibrosis, and were ineffective or only slightly effective in inhibiting vessel occlusion. We also found that Azaindole and Fasudil affected actin cytoskeleton and protein expression in mouse peritoneal macrophages ConclusionResults of these studies might help in development of anti-chronic rejection therapy for clinical use.

Молекулы клеточной адгезии ICAM-1 и VCAM-1 при инфекционной патологии

Endothelial activation is an important part of immune response to an infection. Processes of leukocytes migration in the tissue of blood vessels depend on endothelium condition. With the activation of the endothelium followed by its dysfunction, there is an increase in expression on the membrane of endothelial cells of molecules of cell adhesion, in particular, the molecule of intercellular adhesion molecule 1-type (ICAM-1) and the molecule of adhesion of vascular endothelium of the 1-type (vascular cell adhesion molecule 1 - VCAM-1), which provide a strong adhesion of leukocytes to the endothelium. Soluble forms of these molecules can be considered as surrogate biomarkers of endothelial activation. The review provides the data of the world literature of changes in the expression of these biomarkers in sepsis, hemolytic-uremic syndrome, malaria, dengue haemor-rhagic fever, boutonneuse fever, viral hepatitis, tuberculosis. Despite the ambiguous results it can be concluded that ICAM-1 и VCAM-1 are promising for further study both to foresee the course and outcomes in different infectious pathology, and to develop new therapeutic strategy.

Recognition of Coronary Atherosclerotic Plaque Tissue on Intravascular Ultrasound Images by Using Misclassification Sensitive Training of Discriminative Restricted Boltzmann Machine

Coronary atherosclerotic plaque has been extensively studied in pathological research. Improving the evaluation of vulnerable rupture is important to prevent acute heart failure. Intravascular ultrasound (IVUS) method is one of techniques to acquire information about atherosclerotic plaque, which is backscattered ultrasound signal sensed by IVUS transducer. The vessel structure and tissue components are then characterized in relation to the acquired signals. In this study, eight human coronary vessel sections are involved, and we use discriminative restricted Boltzmann machine (RBM) to classify coronary tissues as a target classifier. The quantization domain of IVUS signals are used to extract binary features for adapting Gaussian model of RBM. In addition, we propose a misclassification sensitive training of disRBM to deal with the class imbalances. The results are compared to the conventional integrated backscattered IVUS method (IB-IVUS) and the cost sensitive neural network for the same tasks.

Why does vitreoretinal traction create macular oedema?

A 65-year-old taxi driver was referred due to blurry vision in the right eye of two-day duration and described his symptoms as if he was ‘looking through ice’. There were no other symptoms. Visual acuity (VA) was 0.7 in the right eye and 0.8 in the left eye. Slit lamp examination revealed macular oedema in the right eye (Fig. 1). Optical coherent tomography (OCT, Topcon 3D OCT-2000 FA plus) revealed vitreomacular traction (VMT) and macular oedema involving the inner layers of the retina in the right eye. In the left eye, a partial posterior vitreous detachment (PVD) was seen, without VMT (Fig. 1). A diagnosis of VMT syndrome, due to incomplete PVD, was entertained. The patient was advised of the situation and did not receive any treatment. A follow-up appointment was scheduled few weeks later. Before that appointment, he came to the clinic complaining of floaters in the right eye. On examination, the vision was 1.0 in both eyes, a Weiss ring was visible on biomicroscopy in the vitreous cavity of the right eye and there were no signs of maculopathy. Optical coherent tomography (OCT) imaging was normal, except for minimal shadows on the image due to vitreous floaters. He was diagnosed with complete PVD. Vitreomacular traction is caused by an incomplete PVD where the vitreous remains attached to the posterior retina, exerting traction on the macula. The traction causes retinal distortion and can cause various macular disorders, including cystoid macular oedema, macular hole and epiretinal membrane (Duker et al. 2013). In our case, the initial OCT image showed clear vitreous traction on the central macular area resulting in distortion and macular oedema. No epiretinal membrane was noted. The distortion is easy to understand, but what is the mechanism that translates mechanical traction into tissue oedema? Newton's third law states: ‘To every action there is always opposed an equal reaction’ (Newton 1726), which in current terminology means that for every force, there is a counter-force acting in the opposite direction. The force exerted by the vitreous gel pulls anteriorly on the retina, and this is met by an equal force in the retina pulling posteriorly towards the back of the eye. The opposite pulling forces lower the hydrostatic pressure in the tissue between the forces (Fig. 2). Starling's law describes the formation of oedema in tissues. It states that fluid transport between tissue and blood vessels is controlled by hydrostatic and osmotic forces. The hydrostatic pressure difference (created by the heart) between blood vessels and tissue drives water down a pressure gradient into the interstitial space. The osmotic pressure difference pulls water from tissue into blood vessels due to high osmotic activity of the macromolecules in blood. In normal conditions, the hydrostatic and osmotic pressure differences between tissue and blood vessels are equal and opposite and no net transport of water takes place; oedema is neither formed nor reduced (Hall & Guyton 2011). This steady state is upset by the VMT. The traction reduces the hydrostatic pressure in the retina, thus increasing the pressure difference between blood vessel and retinal tissue. Water flows down this pressure gradient and accumulates in the tissue as oedema. Water accumulation lowers the osmotic pressure in the interstitial space and increases the osmotic pressure difference, until a new equilibrium is established between the hydrostatic and osmotic pressure differences. At this time, the net transport of water again is zero and the tissue reaches a steady state – with macular oedema (Stefánsson 2009). Vitreomacular traction (VMT) with macular oedema can be managed conservatively as spontaneous resolution occurs in some cases. When the VMT is persistent, it is usually treated surgically with pars plana vitrectomy, but pharmacological vitreolysis with ocriplasmin and pneumatic release with intravitreal gas have also shown to be effective (Jackson et al. 2013). Surgical, spontaneous, pneumatic or enzymatic release of the VMT reverses the situation described above. Hydrostatic pressure in the retina increases back to normal, water flows back into the blood vessels, and the macular oedema disappears.

Sensing of silver nanoparticles on/in endothelial cells using atomic force spectroscopy.

Endothelial cells, due to their location, are interesting objects for atomic force spectroscopy study. They constitute a barrier between blood and vessel tissues located deeper, and therefore they are the first line of contact with various substances present in blood, eg, drugs or nanoparticles. This work intends to verify whether the mechanical response of immortalized human umbilical vein endothelial cells (EA.hy926), when exposed to silver nanoparticles, as measured using force spectroscopy, could be effectively used as a bio-indicator of the physiological state of the cells. Silver nanoparticles were characterized with transmission electron microscopy and dynamic light scattering techniques. Tetrazolium salt reduction test was used to determine cell viability after treatment with silver nanoparticles. An elasticity of native cells was examined in the Hanks' buffer whereas fixed cells were softly fixed with formaldehyde. Additional aspect of the work is the comparative force spectroscopy utilizing AFM probes of ball-shape and conical geometries, in order to understand what changes in cell elasticity, caused by SNPs, were detectable with each probe. As a supplement to elasticity studies, cell morphology observation by atomic force microscopy and detection of silver nanoparticles inside cells using transmission electron microscopy were also performed. Cells exposed to silver nanoparticles at the highest selected concentrations (3.6μg/mL, 16μg/mL) are less elastic. It may be associated with the reorganization of the cellular cytoskeleton and the "strengthening" of the cell cortex caused by presence of silver nanoparticles. This observation does not depend on cell fixation. Agglomerates of silver nanoparticles were observed on the cell membrane as well as inside the cells.

FORCED WAVES PROPAGATION IN GREAT LIVING ARTERIES TISSUES

Starting from experimental data, this work exploit the similarity of pressure and axial wave’s propagation of both pressure and axial waves in large vessel (e.g., aorta) with the solution of a mathematical model developed to describe the motion of acoustic waves in solid. In particular, we show how the motion parameters derived by fitting the experimental data measured in living dog arteries are related to mechanical properties of the vessel tissue using the same theoretical model. Furthermore, we briefly discuss the consequence on the predicted forced wave motion of inferring from experimental data a phase velocity depending from frequency.

Abstract 692: Development of the Gene Therapy With CRE Decoy ODN to Prevent Vascular Intimal Hyperplasia

Background: Intimal hyperplasia (IH) is the main cause of vein graft stenosis or failure after bypass surgery. However, in the previous study, no therapeutic targets for the treatment of IH have been identified. Our recent research have been reported that the inhibition of Cyclic adenosine monophosphate response-element (CRE) binding protein (CREB) activation is a key role for vein graft IH. Objective: In consideration of future clinical application, we focused on decoy oligodeoxynucleotide (ODN) transfection as gene therapy strategy for suppressing IH. The goal of the present study is to identify whether the CRE decoy ODN had the therapeutic efficacy for suppressing IH. Methods: We developed phosphorothioate CRE decoy ODN and checked binding ability to a CRE sequence using CREB transcription assay . We chose a decoy ODN having high first-binding ability and transfected it to vascular smooth muscle cell(VSMC) in vitro. Proliferation was assessed using MTS assay and migration was assessed using a modified Boyden-chamber assay. We examined CRE activity using Luciferase reporter gene assay. We checked expression of mRNAs using qRT-PCR. In wire-injury mouse model(C57BL6,n=6), CRE decoy ODN was transfected to injured vessel wall using ultrasound-sonoporation method in vivo. Results: CREB transcription factor assay showed CRE decoy had about 80 folds binding ability of control decoy in IC50 value (vs.control,n=5). Transfer of CRE decoy ODN resulted in significantly downregulated CRE activity(vs.control,P<.01,n=12) and inhibited VSMC proliferation (vs.control,P<.01,n=12) and migration (vs.control,P<.01,n=5). In a wire-injury mouse model, histopathological analysis revealed that transfer of the CRE decoy ODN significantly repressed IH whereas intensive IH was observed in the control group. In this vessel tissue, Levels of mRNA CCNA2 and Bcl2 were significantly lower in CRE decoy group than in control group(n=6,P<.01,respectively). CRE-activated gene expression was strongly repressed. Conclusions: The present result suggested that CRE decoy ODN inhibiting CREB function provide an effective therapeutic approach to suppressing IH.

Gene expression profiles of ion channels and receptors in mouse resistance arteries: Effects of cell type, vascular bed, and age.

Receptors and ion channels of smooth muscle cells (SMCs) and endothelial cells (ECs) are integral to the regulation of vessel diameter and tissue blood flow. Physiological roles of ion channels and receptors in skeletal muscle and mesenteric arteries have been identified; however, their gene expression profiles are undefined. We tested the hypothesis that expression profiles for ion channels and receptors governing vascular reactivity vary with cell type, vascular bed, and age. Mesenteric and superior epigastric arteries were dissected from Old (24-26months) and Young (3-6months) C57BL/6J mice. ECs and SMCs were collected for analysis with custom qRT-PCR arrays to determine expression profiles of 80 ion channel and receptor genes. Bioinformatics analyses were applied to gain insight into functional interactions. We identified 68 differences in gene expression with respect to cell type, vessel type, and age. Heat maps illustrate differential expression, and distance matrices predict patterns of coexpression. Gene networks based upon protein-protein interaction datasets and KEGG pathways illustrate biological processes affected by specific differences in gene expression. Differences in gene expression profiles are most pronounced between microvascular ECs and SMCs with subtle variations between vascular beds and age groups.

Thinking on the Training of Uniportal Video-assisted Thoracic Surgery

近年来，单孔胸腔镜技术迅速发展，已成为全球外科发展方向。单孔胸腔镜外科医师的针对性，规范化、系统化培训已成为重要的课题，技术培训是保证手术安全性的必不可少的重要环节。单孔电视胸腔镜技术培训应包括：由临床大中心经验丰富的专家直接面对面的教授手术技巧，或聘请专家导师前往学员所在单位进行针对性现场指导，这是一个代表性的、不可缺少的重要环节。网络视频通常也可以作为培训的方式。目前的技术提供了很多模拟训练，诸如：体外模拟器，人工合成胸腔、肺模型，动物实验，3D和VR技术能够为学习者提供各种层面的培训需求。对于大样本量的培训中心，短期的集中培训和中长期的系统性培训目前越来越受关注。根据学员的分级评估，采用多元化的培训模式，因材施教的针对性训练，有助于提高培训效果。我科在单孔胸腔镜外科医师培训方面做了一些工作，积累了一些培训经验，我们认为这样的培训是可行且完全有必要的。

A Hopeful Prospect of Riociguat as a Soluble Guanylate Cyclase Stimulator for Management of Pressure Ulcers.

Pressure ulcer remains as a common problem, especially developed in disabled patients and hence, subjected to continuous pressure for prolonged periods of time. Most of the studies investigating the preventive and therapeutic approaches have focused on wound cleansing, dressing and supportive strategies, as well as pharmacological therapy including zinc sulphate, vitamin A or phenytoin. Despite such efforts, pressure ulcer continues to impair the life quality and expectancy. Thus involving in the paradigm shift in biomedical studies, the recent ones focus on biological signaling pathways involving nitric oxide (NO)- soluble guanylatecyclase (sGC)- cyclic guanosine monophosphate (cGMP) contributing in vasodilation, reperfusion and oxygen delivery. Literatures review focusing on NO/sGC/cGMP pathway was performed as well as seeking themolecular biology aspects inKyoto Encyclopedia of genes and genomes (KEGG). NO is an important signaling molecule activating sGC and cGMP production, which is a mediator of vasodilation and platelet inhibition. Considering the subject, it could be hypothesized that the application of sGC stimulators and activators is a very curious strategy for pressure ulcer healing. It is well known that pressure and shear forces usually produce the blood vessel obstruction, inducing ischemia and tissue necrosis and in pathologic states, damaged endothelium leads to a reduced synthesis of NO and inadequate oxygen supply contributing to delayed wound healing. Riociguat is the first FDA approved agent of new class of sGC stimulators, involving in activation of sGC both in presence and absence of NO. The findings of this review confirm that Riociguat could start a new therapeutic approach for pressure ulcer treatment even with dysfunctional endothelium.

Mechanical Characterization of the Vessel Wall by Data Assimilation of Intravascular Ultrasound Studies

Atherosclerotic plaque rupture and erosion are the most important mechanisms underlying the sudden plaque growth, responsible for acute coronary syndromes and even fatal cardiac events. Advances in the understanding of the culprit plaque structure and composition are already reported in the literature, however, there is still much work to be done toward in-vivo plaque visualization and mechanical characterization to assess plaque stability, patient risk, diagnosis and treatment prognosis. In this work, a methodology for the mechanical characterization of the vessel wall plaque and tissues is proposed based on the combination of intravascular ultrasound (IVUS) imaging processing, data assimilation and continuum mechanics models within a high performance computing (HPC) environment. Initially, the IVUS study is gated to obtain volumes of image sequences corresponding to the vessel of interest at different cardiac phases. These sequences are registered against the sequence of the end-diastolic phase to remove transversal and longitudinal rigid motions prescribed by the moving environment due to the heartbeat. Then, optical flow between the image sequences is computed to obtain the displacement fields of the vessel (each associated to a certain pressure level). The obtained displacement fields are regarded as observations within a data assimilation paradigm, which aims to estimate the material parameters of the tissues within the vessel wall. Specifically, a reduced order unscented Kalman filter is employed, endowed with a forward operator which amounts to address the solution of a hyperelastic solid mechanics model in the finite strain regime taking into account the axially stretched state of the vessel, as well as the effect of internal and external forces acting on the arterial wall. Due to the computational burden, a HPC approach is mandatory. Hence, the data assimilation and computational solid mechanics computations are parallelized at three levels: (i) a Kalman filter level; (ii) a cardiac phase level; and (iii) a mesh partitioning level. To illustrate the capabilities of this novel methodology toward the in-vivo analysis of patient-specific vessel constituents, mechanical material parameters are estimated using in-silico and in-vivo data retrieved from IVUS studies. Limitations and potentials of this approach are exposed and discussed.

The Effect of Passive Smoking for Different Periods on Histopathological Central Nervous System of Male Mice Mus musculus

The research aims to show the histopathological changes caused by passive smoking in the central nervous system tissues. Laboratory animals were offered for (10, 20) weeks for a period of passive smoking (2,4) hours per day. Histopathological examination of brain and spinal cord showed the presence of degeneration and necrotic neurons in the brain tissue and spinal cord in addition to vacuolation and heavy hemorrhage in the brain tissue and congestion of blood vessels of the brain and spinal cord and clarity clot inside the blood vessel of the brain tissue.

Receiver-Operating Characteristic Analysis of Eigen-Based Clutter Filters for Ultrasound Color Flow Imaging.

The eigen-based filter has theoretically established itself as a potent solution in ultrasound color flow imaging (CFI) for combating against clutter arising from moving tissues. Yet, it remains poorly understood on how much gain in flow detection sensitivity and specificity can be delivered by this adaptive clutter filter. Here, we investigated the receiver operating characteristic (ROC) of the eigen-based clutter filter to statistically evaluate its efficacy. Our investigation was conducted using a new vascular phantom testbed that incorporated both intrinsic tissue motion (vessel pulsation: 7.58 cm/s peak velocity) and extrinsic tissue motion (vibration: 5-Hz frequency, 2.98 cm/s peak velocity), as well as pulsatile flow (pulse rate: 60 beats/min; systolic flow rate: 6.5 mL/s). The eigen-filter (single-ensemble formulation) was applied to CFI raw data sets obtained from the phantom's short-axis view (slow-time ensemble size: 12; pulse repetition frequency: 2 kHz; and ultrasound frequency: 5 MHz), and post-filter Doppler power was compared between flow and tissue regions. Results show that, in the presence of vessel pulsation and tissue vibration, the eigen-filter yielded a high true positive rate in depicting flow pixels in CFI frames (0.945 and 0.917, respectively, during peak systole and end diastole at 60° beam-flow angle), while maintaining a low false alarm rate (0.10) in rendering tissue pixels. Also, the eigen-filter posed ROC curves whose area under curve was higher than those for the polynomial regression filter (statistically significant; t-test p values were less than 0.05). These findings serve well to substantiate the merit of using eigen-filters to enhance the vascular visualization capability of CFI.

Comparison of Optical Coherence Tomography Angiography and Laser Speckle Flowgraphy for the Diagnosis of Normal-Tension Glaucoma.

Purpose To compare optical coherence tomography angiography (OCT-A) and laser speckle flowgraphy (LSFG) for the diagnosis of normal-tension glaucoma (NTG). Methods Twenty-eight eyes of 28 patients with NTG and 25 eyes of 25 normal subjects matched for age, refractive errors, systemic blood pressure, and central corneal thickness were evaluated. OCT-A was used to measure whole image vessel density, inside disc vessel density, and peripapillary vessel density; using LSFG, mean blur rate (MBR) inside the whole optic nerve head (ONH) area (MBRA), and MBR of the vessel area (MBRV) and tissue area (MBRT) inside the ONH, were determined. Receiver operating characteristic (ROC) curves and areas under the ROC (AUROC) were used to assess the diagnostic ability of each variable. Results The AUROC for OCT-A whole image vessel density (0.950) was significantly greater than that for OCT-A peripapillary vessel density (0.830) and for all LSFG parameters (MBRA = 0.793, MBRV = 0.601, and MBRT = 0.61) (P < 0.001). The AUROC for OCT-A inside disc vessel density (0.931) was significantly greater than that for all LSFG parameters (P < 0.005). Conclusions OCT-A vessel density had a higher glaucoma diagnostic ability compared to all LSFG parameters in patients with NTG.