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Sample records for blood vessel remodeling

  1. Synergistic actions of blocking angiopoietin-2 and tumor necrosis factor-α in suppressing remodeling of blood vessels and lymphatics in airway inflammation.

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    Le, Catherine T K; Laidlaw, Grace; Morehouse, Christopher A; Naiman, Brian; Brohawn, Philip; Mustelin, Tomas; Connor, Jane R; McDonald, Donald M

    2015-11-01

    Remodeling of blood vessels and lymphatics are prominent features of sustained inflammation. Angiopoietin-2 (Ang2)/Tie2 receptor signaling and tumor necrosis factor-α (TNF)/TNF receptor signaling are known to contribute to these changes in airway inflammation after Mycoplasma pulmonis infection in mice. We determined whether Ang2 and TNF are both essential for the remodeling on blood vessels and lymphatics, and thereby influence the actions of one another. Their respective contributions to the initial stage of vascular remodeling and sprouting lymphangiogenesis were examined by comparing the effects of function-blocking antibodies to Ang2 or TNF, given individually or together during the first week after infection. As indices of efficacy, vascular enlargement, endothelial leakiness, venular marker expression, pericyte changes, and lymphatic vessel sprouting were assessed. Inhibition of Ang2 or TNF alone reduced the remodeling of blood vessels and lymphatics, but inhibition of both together completely prevented these changes. Genome-wide analysis of changes in gene expression revealed synergistic actions of the antibody combination over a broad range of genes and signaling pathways involved in inflammatory responses. These findings demonstrate that Ang2 and TNF are essential and synergistic drivers of remodeling of blood vessels and lymphatics during the initial stage of inflammation after infection. Inhibition of Ang2 and TNF together results in widespread suppression of the inflammatory response. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  2. Role of arginase in vessel wall remodeling

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    William eDurante

    2013-05-01

    Full Text Available Arginase metabolizes the semi-essential amino acid L-arginine to L-ornithine and urea. There are two distinct isoforms of arginase, arginase I and II, which are encoded by separate genes and display differences in tissue distribution, subcellular localization, and molecular regulation. Blood vessels express both arginase I and II but their distribution appears to be cell-, vessel-, and species-specific. Both isoforms of arginase are induced by numerous pathologic stimuli and contribute to vascular cell dysfunction and vessel wall remodeling in several diseases. Clinical and experimental studies have documented increases in the expression and/or activity of arginase I or II in blood vessels following arterial injury and in pulmonary and arterial hypertension, aging, and atherosclerosis. Significantly, pharmacological inhibition or genetic ablation of arginase in animals ameliorates abnormalities in vascular cells and normalizes blood vessel architecture and function in all of these pathological states. The detrimental effect of arginase in vascular remodeling is attributable to its ability to stimulate vascular smooth muscle cell and endothelial cell proliferation, and collagen deposition by promoting the synthesis of polyamines and L-proline, respectively. In addition, arginase adversely impacts arterial remodeling by directing macrophages towards an inflammatory phenotype. Moreover, the proliferative, fibrotic, and inflammatory actions of arginase in the vasculature are further amplified by its capacity to inhibit nitric oxide synthesis by competing with nitric oxide synthase for substrate, L-arginine. Pharmacologic or molecular approaches targeting specific isoforms of arginase represent a promising strategy in treating obstructive fibroproliferative vascular disease.

  3. Chronic mild hypoxia promotes profound vascular remodeling in spinal cord blood vessels, preferentially in white matter, via an α5β1 integrin-mediated mechanism.

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    Halder, Sebok K; Kant, Ravi; Milner, Richard

    2018-05-01

    Spinal cord injury (SCI) leads to rapid destruction of neuronal tissue, resulting in devastating motor and sensory deficits. This is exacerbated by damage to spinal cord blood vessels and loss of vascular integrity. Thus, approaches that protect existing blood vessels or stimulate the growth of new blood vessels might present a novel approach to minimize loss or promote regeneration of spinal cord tissue following SCI. In light of the remarkable power of chronic mild hypoxia (CMH) to stimulate vascular remodeling in the brain, the goal of this study was to examine how CMH (8% O 2 for up to 7 days) affects blood vessel remodeling in the spinal cord. We found that CMH promoted the following: (1) endothelial proliferation and increased vascularity as a result of angiogenesis and arteriogenesis, (2) increased vascular expression of the angiogenic extracellular matrix protein fibronectin as well as concomitant increases in endothelial expression of the fibronectin receptor α5β1 integrin, (3) strongly upregulated endothelial expression of the tight junction proteins claudin-5, ZO-1 and occludin and (4) astrocyte activation. Of note, the vascular remodeling changes induced by CMH were more extensive in white matter. Interestingly, hypoxic-induced vascular remodeling in spinal cord blood vessels was markedly attenuated in mice lacking endothelial α5 integrin expression (α5-EC-KO mice). Taken together, these studies demonstrate the considerable remodeling potential of spinal cord blood vessels and highlight an important angiogenic role for the α5β1 integrin in promoting endothelial proliferation. They also imply that stimulation of the α5β1 integrin or controlled use of mild hypoxia might provide new approaches for promoting angiogenesis and improving vascular integrity in spinal cord blood vessels.

  4. Low level arsenic promotes progressive inflammatory angiogenesis and liver blood vessel remodeling in mice

    International Nuclear Information System (INIS)

    Straub, Adam C.; Stolz, Donna B.; Vin, Harina; Ross, Mark A.; Soucy, Nicole V.; Klei, Linda R.; Barchowsky, Aaron

    2007-01-01

    The vascular effects of arsenic in drinking water are global health concerns contributing to human disease worldwide. Arsenic targets the endothelial cells lining blood vessels, and endothelial cell activation or dysfunction may underlie the pathogenesis of both arsenic-induced vascular diseases and arsenic-enhanced tumorigenesis. The purpose of the current studies was to demonstrate that exposing mice to drinking water containing environmentally relevant levels of arsenic promoted endothelial cell dysfunction and pathologic vascular remodeling. Increased angiogenesis, neovascularization, and inflammatory cell infiltration were observed in Matrigel plugs implanted in C57BL/6 mice following 5-week exposures to 5-500 ppb arsenic [Soucy, N.V., Mayka, D., Klei, L.R., Nemec, A.A., Bauer, J.A., Barchowsky, A., 2005. Neovascularization and angiogenic gene expression following chronic arsenic exposure in mice. Cardiovasc.Toxicol 5, 29-42]. Therefore, functional in vivo effects of arsenic on endothelial cell function and vessel remodeling in an endogenous vascular bed were investigated in the liver. Liver sinusoidal endothelial cells (LSEC) became progressively defenestrated and underwent capillarization to decrease vessel porosity following exposure to 250 ppb arsenic for 2 weeks. Sinusoidal expression of PECAM-1 and laminin-1 proteins, a hallmark of capillarization, was also increased by 2 weeks of exposure. LSEC caveolin-1 protein and caveolae expression were induced after 2 weeks of exposure indicating a compensatory change. Likewise, CD45/CD68-positive inflammatory cells did not accumulate in the livers until after LSEC porosity was decreased, indicating that inflammation is a consequence and not a cause of the arsenic-induced LSEC phenotype. The data demonstrate that the liver vasculature is an early target of pathogenic arsenic effects and that the mouse liver vasculature is a sensitive model for investigating vascular health effects of arsenic

  5. Molecular imaging of tumor blood vessels in prostate cancer.

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    Tilki, Derya; Seitz, Michael; Singer, Bernhard B; Irmak, Ster; Stief, Christian G; Reich, Oliver; Ergün, Süleyman

    2009-05-01

    In the past three decades many efforts have been undertaken to understand the mechanisms of tumor angiogenesis. The introduction of anti-angiogenic drugs in tumor therapy during the last few years necessitates the establishment of new techniques enabling molecular imaging of tumor vascular remodelling. The determination of tumor size as commonly used is not appropriate since the extended necrosis under anti-angiogenic therapy does not necessarily result in the reduction of tumor diameter. The basis for the molecular imaging of tumor blood vessels is the remodelling of the tumor vessels under anti-angiogenic therapy which obviously occurs at an early stage and seems to be a convincing parameter. Beside the enormous progress in this field during the last few years the resolution is still not high enough to evaluate the remodelling of the micro tumor vessels. New imaging approaches combining specific molecular markers for tumor vessels with the different imaging techniques are needed to overcome this issue as exemplarily discussed for prostate cancer in this review. Molecular contrast agents targeting the vasculature will allow clinicians the visualization of vascular remodelling processes taking place under anti-angiogenic therapy and improve tumor diagnosis and follow-up.

  6. Vascular remodeling: A redox-modulated mechanism of vessel caliber regulation.

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    Tanaka, Leonardo Y; Laurindo, Francisco R M

    2017-08-01

    Vascular remodeling, i.e. whole-vessel structural reshaping, determines lumen caliber in (patho)physiology. Here we review mechanisms underlying vessel remodeling, with emphasis in redox regulation. First, we discuss confusing terminology and focus on strictu sensu remodeling. Second, we propose a mechanobiological remodeling paradigm based on the concept of tensional homeostasis as a setpoint regulator. We first focus on shear-mediated models as prototypes of remodeling closely dominated by highly redox-sensitive endothelial function. More detailed discussions focus on mechanosensors, integrins, extracellular matrix, cytoskeleton and inflammatory pathways as potential of mechanisms potentially coupling tensional homeostasis to redox regulation. Further discussion of remodeling associated with atherosclerosis and injury repair highlights important aspects of redox vascular responses. While neointima formation has not shown consistent responsiveness to antioxidants, vessel remodeling has been more clearly responsive, indicating that despite the multilevel redox signaling pathways, there is a coordinated response of the whole vessel. Among mechanisms that may orchestrate redox pathways, we discuss roles of superoxide dismutase activity and extracellular protein disulfide isomerase. We then discuss redox modulation of aneurysms, a special case of expansive remodeling. We propose that the redox modulation of vascular remodeling may reflect (1) remodeling pathophysiology is dominated by a particularly redox-sensitive cell type, e.g., endothelial cells (2) redox pathways are temporospatially coordinated at an organ level across distinct cellular and acellular structures or (3) the tensional homeostasis setpoint is closely connected to redox signaling. The mechanobiological/redox model discussed here can be a basis for improved understanding of remodeling and helps clarifying mechanisms underlying prevalent hard-to-treat diseases. Copyright © 2017 Elsevier Inc. All

  7. A Computational Model Predicting Disruption of Blood Vessel Development

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    Vascular development is a complex process regulated by dynamic biological networks that vary in topology and state across different tissues and developmental stages. Signals regulating de novo blood vessel formation (vasculogenesis) and remodeling (angiogenesis) come from a varie...

  8. Tumor Blood Vessel Dynamics

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    Munn, Lance

    2009-11-01

    ``Normalization'' of tumor blood vessels has shown promise to improve the efficacy of chemotherapeutics. In theory, anti-angiogenic drugs targeting endothelial VEGF signaling can improve vessel network structure and function, enhancing the transport of subsequent cytotoxic drugs to cancer cells. In practice, the effects are unpredictable, with varying levels of success. The predominant effects of anti-VEGF therapies are decreased vessel leakiness (hydraulic conductivity), decreased vessel diameters and pruning of the immature vessel network. It is thought that each of these can influence perfusion of the vessel network, inducing flow in regions that were previously sluggish or stagnant. Unfortunately, when anti-VEGF therapies affect vessel structure and function, the changes are dynamic and overlapping in time, and it has been difficult to identify a consistent and predictable normalization ``window'' during which perfusion and subsequent drug delivery is optimal. This is largely due to the non-linearity in the system, and the inability to distinguish the effects of decreased vessel leakiness from those due to network structural changes in clinical trials or animal studies. We have developed a mathematical model to calculate blood flow in complex tumor networks imaged by two-photon microscopy. The model incorporates the necessary and sufficient components for addressing the problem of normalization of tumor vasculature: i) lattice-Boltzmann calculations of the full flow field within the vasculature and within the tissue, ii) diffusion and convection of soluble species such as oxygen or drugs within vessels and the tissue domain, iii) distinct and spatially-resolved vessel hydraulic conductivities and permeabilities for each species, iv) erythrocyte particles advecting in the flow and delivering oxygen with real oxygen release kinetics, v) shear stress-mediated vascular remodeling. This model, guided by multi-parameter intravital imaging of tumor vessel structure

  9. Effect of antiprogesterone RU486 on VEGF expression and blood vessel remodeling on ovarian follicles before ovulation.

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    Annunziata Mauro

    Full Text Available BACKGROUND: The success of ovarian follicle growth and ovulation is strictly related to the development of an adequate blood vessel network required to sustain the proliferative and endocrine functions of the follicular cells. Even if the Vascular Endothelial Growth Factor (VEGF drives angiogenesis before ovulation, the local role exerted by Progesterone (P₄ remains to be clarified, in particular when its concentration rapidly increases before ovulation. AIM: This in vivo study was designed to clarify the effect promoted by a P₄ receptor antagonist, RU486, on VEGF expression and follicular angiogenesis before ovulation, in particular, during the transition from pre to periovulatory follicles induced by human Chorionic Gonadotropins (hCG administration. MATERIAL AND METHODS: Preovulatory follicle growth and ovulation were pharmacologically induced in prepubertal gilts by combining equine Chorionic Gonadotropins (eCG and hCG used in the presence or absence of RU486. The effects on VEGF expression were analyzed using biochemical and immunohistochemical studies, either on granulosa or on theca layers of follicles isolated few hours before ovulation. This angiogenic factor was also correlated to follicular morphology and to blood vessels architecture. RESULTS AND CONCLUSIONS: VEGF production, blood vessel network and follicle remodeling were impaired by RU486 treatment, even if the cause-effect correlation remains to be clarified. The P₄ antagonist strongly down-regulated theca VEGF expression, thus, preventing most of the angiogenic follicle response induced by hCG. RU486-treated follicles displayed a reduced vascular area, a lower rate of endothelial cell proliferation and a reduced recruitment of perivascular mural cells. These data provide important insights on the biological role of RU486 and, indirectly, on steroid hormones during periovulatory follicular phase. In addition, an in vivo model is proposed to evaluate how periovulatory

  10. Thyroid hormone promotes remodeling of coronary resistance vessels.

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    Olga V Savinova

    Full Text Available Low thyroid hormone (TH function has been linked to impaired coronary blood flow, reduced density of small arterioles, and heart failure. Nonetheless, little is known about the mechanisms by which THs regulate coronary microvascular remodeling. The current study examined the initial cellular events associated with coronary remodeling induced by triiodothyronine (T3 in hypothyroid rats. Rats with established hypothyroidism, eight weeks after surgical thyroidectomy (TX, were treated with T3 for 36 or 72 hours. The early effects of T3 treatment on coronary microvasculature were examined morphometrically. Gene expression changes in the heart were assessed by quantitative PCR Array. Hypothyroidism resulted in arteriolar atrophy in the left ventricle. T3 treatment rapidly induced small arteriolar muscularization and, within 72 hours, restored arteriolar density to control levels. Total length of the capillary network was not affected by TX or T3 treatment. T3 treatment resulted in the coordinate regulation of Angiopoietin 1 and 2 expression. The response of Angiopoietins was consistent with vessel enlargement. In addition to the well known effects of THs on vasoreactivity, these results suggest that THs may affect function of small resistance arteries by phenotypic remodeling of vascular smooth muscle cells (VSMC.

  11. Bio-Adaption between Magnesium Alloy Stent and the Blood Vessel: A Review.

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    Ma, Jun; Zhao, Nan; Betts, Lexxus; Zhu, Donghui

    2016-09-01

    Biodegradable magnesium (Mg) alloy stents are the most promising next generation of bio-absorbable stents. In this article, we summarized the progresses on the in vitro studies, animal testing and clinical trials of biodegradable Mg alloy stents in the past decades. These exciting findings led us to propose the importance of the concept "bio-adaption" between the Mg alloy stent and the local tissue microenvironment after implantation. The healing responses of stented blood vessel can be generally described in three overlapping phases: inflammation, granulation and remodeling. The ideal bio-adaption of the Mg alloy stent, once implanted into the blood vessel, needs to be a reasonable function of the time and the space/dimension. First, a very slow degeneration of mechanical support is expected in the initial four months in order to provide sufficient mechanical support to the injured vessels. Although it is still arguable whether full mechanical support in stented lesions is mandatory during the first four months after implantation, it would certainly be a safety design parameter and a benchmark for regulatory evaluations based on the fact that there is insufficient human in vivo data available, especially the vessel wall mechanical properties during the healing/remodeling phase. Second, once the Mg alloy stent being degraded, the void space will be filled by the regenerated blood vessel tissues. The degradation of the Mg alloy stent should be 100% completed with no residues, and the degradation products (e.g., ions and hydrogen) will be helpful for the tissue reconstruction of the blood vessel. Toward this target, some future research perspectives are also discussed.

  12. Bio-Adaption between Magnesium Alloy Stent and the Blood Vessel: A Review

    Science.gov (United States)

    Ma, Jun; Zhao, Nan; Betts, Lexxus; Zhu, Donghui

    2016-01-01

    Biodegradable magnesium (Mg) alloy stents are the most promising next generation of bio-absorbable stents. In this article, we summarized the progresses on the in vitro studies, animal testing and clinical trials of biodegradable Mg alloy stents in the past decades. These exciting findings led us to propose the importance of the concept “bio-adaption” between the Mg alloy stent and the local tissue microenvironment after implantation. The healing responses of stented blood vessel can be generally described in three overlapping phases: inflammation, granulation and remodeling. The ideal bio-adaption of the Mg alloy stent, once implanted into the blood vessel, needs to be a reasonable function of the time and the space/dimension. First, a very slow degeneration of mechanical support is expected in the initial four months in order to provide sufficient mechanical support to the injured vessels. Although it is still arguable whether full mechanical support in stented lesions is mandatory during the first four months after implantation, it would certainly be a safety design parameter and a benchmark for regulatory evaluations based on the fact that there is insufficient human in vivo data available, especially the vessel wall mechanical properties during the healing/remodeling phase. Second, once the Mg alloy stent being degraded, the void space will be filled by the regenerated blood vessel tissues. The degradation of the Mg alloy stent should be 100% completed with no residues, and the degradation products (e.g., ions and hydrogen) will be helpful for the tissue reconstruction of the blood vessel. Toward this target, some future research perspectives are also discussed. PMID:27698548

  13. Extensive vascular remodeling in the spinal cord of pre-symptomatic experimental autoimmune encephalomyelitis mice; increased vessel expression of fibronectin and the α5β1 integrin

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    Boroujerdi, Amin; Welser-Alves, Jennifer V.; Milner, Richard

    2013-01-01

    Alterations in vascular structure and function are a central component of demyelinating disease. In addition to blood-brain barrier (BBB) breakdown, which occurs early in the course of disease, recent studies have described angiogenic remodeling, both in multiple sclerosis tissue and in the mouse demyelinating model, experimental autoimmune encephalomyelitis (EAE). As the precise timing of vascular remodeling in demyelinating disease has yet to be fully defined, the purpose of the current study was to define the time-course of these events in the MOG35-55 EAE model. Quantification of endothelial cell proliferation and vessel density revealed that a large part of angiogenic remodeling in cervical spinal cord white matter occurs during the pre-symptomatic phase of EAE. At the height of vascular remodeling, blood vessels in the cervical spinal cord showed strong transient upregulation of fibronectin and the α5β1 integrin. In vitro experiments revealed that α5 integrin inhibition reduced brain endothelial cell proliferation under inflammatory conditions. Interestingly, loss of vascular integrity was evident in all vessels during the first 4–7 days post-immunization, but after 14 days, was localized predominantly to venules. Taken together, our data demonstrate that extensive vascular remodeling occurs during the pre-symptomatic phase of EAE and point to a potential role for the fibronectin-α5β1 integrin interaction in promoting vascular remodeling during demyelinating disease. PMID:24056042

  14. Remodelling of choroidal blood flow in radiation choroidopathy

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    Kobayashi, Hideo; Muraoka, Kanemitsu; Takahashi, Kyoichi; Sutoh, Noriko [Gunma Univ., Maebashi (Japan). School of Medicine

    1997-02-01

    Two males, aged 68 and 34 years each, presented with radiation retinopathy. One had received radiation therapy to the whole brain for intracranial metastasis of lung carcinoma 29 months before. The other underwent surgery and radiation for melanoma of the upper eyelid 15 years before. When examined by indocyanine green angiography. both cases showed vasoocclusive changes in the choroid involving the choriocapillaris and major vessels in the affected fundus area. In one eye with severe retinal vascular lesions in the superior temporal quadrant, the vortex vein in the quadrant had obliterated. The venous blood in this quadrant was drained into the inferior temporal vortex vein crossing the presumed watershed zone temporal to the macula. Collaterals had formed between choroidal arteries and between choroidal veins. These cases illustrate that choroidal vascular lesions may be present in radiation retinopathy, that the former may be more pronounced than the latter and that choroidal vessels may undergo extensive remodelling to compensate for the disturbed choroidal circulation. (author)

  15. Remodelling of choroidal blood flow in radiation choroidopathy

    International Nuclear Information System (INIS)

    Kobayashi, Hideo; Muraoka, Kanemitsu; Takahashi, Kyoichi; Sutoh, Noriko

    1997-01-01

    Two males, aged 68 and 34 years each, presented with radiation retinopathy. One had received radiation therapy to the whole brain for intracranial metastasis of lung carcinoma 29 months before. The other underwent surgery and radiation for melanoma of the upper eyelid 15 years before. When examined by indocyanine green angiography. both cases showed vasoocclusive changes in the choroid involving the choriocapillaris and major vessels in the affected fundus area. In one eye with severe retinal vascular lesions in the superior temporal quadrant, the vortex vein in the quadrant had obliterated. The venous blood in this quadrant was drained into the inferior temporal vortex vein crossing the presumed watershed zone temporal to the macula. Collaterals had formed between choroidal arteries and between choroidal veins. These cases illustrate that choroidal vascular lesions may be present in radiation retinopathy, that the former may be more pronounced than the latter and that choroidal vessels may undergo extensive remodelling to compensate for the disturbed choroidal circulation. (author)

  16. Absorbed dose calculations to blood and blood vessels for internally deposited radionuclides

    International Nuclear Information System (INIS)

    Akabani, G.; Poston, J.W. Sr.

    1992-01-01

    At present, absorbed dose calculations for radionuclides in the human circulatory system use relatively simple models and are restricted in their applications. To determine absorbed doses to the blood and to the surface of the blood vessel wall, Monte Carlo calculations were performed using the code Electron Gamma Shower (EGS4). Absorbed doses were calculated for the blood and the blood vessel wall (lumen) for different blood vessel sizes. The radionuclides chosen for this study were those commonly used in nuclear medicine. No diffusion of the radionuclide into the blood vessel was or cross fire between blood vessels was assumed. Results are useful in assessing the doses to blood and blood vessel walls for different nuclear medicine procedures

  17. Absorbed dose calculations to blood and blood vessels for internally deposited radionuclides

    International Nuclear Information System (INIS)

    Akabani, G.; Poston, J.W.

    1991-05-01

    At present, absorbed dose calculations for radionuclides in the human circulatory system used relatively simple models and are restricted in their applications. To determine absorbed doses to the blood and to the surface of the blood vessel wall, EGS4 Monte Carlo calculations were performed. Absorbed doses were calculated for the blood and the blood vessel wall (lumen) for different blood vessels sizes. The radionuclides chosen for this study were those commonly used in nuclear medicine. No diffusion of the radionuclide into the blood vessel was assumed nor cross fire between vessel was assumed. Results are useful in assessing the dose in blood and blood vessel walls for different nuclear medicine procedures. 6 refs., 6 figs., 5 tabs

  18. Estimation of center line and diameter of brain blood vessel using three-dimensional blood vessel matching method with head three-dimensional CTA image

    International Nuclear Information System (INIS)

    Maekawa, Masashi; Shinohara, Toshihiro; Nakayama, Masato; Nakasako, Noboru

    2010-01-01

    To support and automate the brain blood vessel disease diagnosis, a novel method to obtain the center line and the diameter of a blood vessel is proposed with a three-dimensional head computed tomographic angiography (CTA) image. Although the line thinning processing with distance transform or gray information is generally used to obtain the blood vessel center line, this method is not essentially one to obtain the center line and tends to yield extra lines depending on CTA images. In this study, the center line of the blood vessel is obtained by tracing the vessel. The blood vessel is traced by sequentially estimating the center point and direction of the blood vessel. The center point and direction of the blood vessel are estimated by taking the correlation between the blood vessel and a solid model of the blood vessel that is designed by considering noise influence. In addition, the vessel diameter is also estimated by correlating the blood vessel and the blood vessel model of which the diameter is variable. The validity of the proposed method is confirmed by experimentally applied the proposed method to an actual three-dimensional head CTA image. (author)

  19. Tumor vessel normalization after aerobic exercise enhances chemotherapeutic efficacy.

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    Schadler, Keri L; Thomas, Nicholas J; Galie, Peter A; Bhang, Dong Ha; Roby, Kerry C; Addai, Prince; Till, Jacob E; Sturgeon, Kathleen; Zaslavsky, Alexander; Chen, Christopher S; Ryeom, Sandra

    2016-10-04

    Targeted therapies aimed at tumor vasculature are utilized in combination with chemotherapy to improve drug delivery and efficacy after tumor vascular normalization. Tumor vessels are highly disorganized with disrupted blood flow impeding drug delivery to cancer cells. Although pharmacologic anti-angiogenic therapy can remodel and normalize tumor vessels, there is a limited window of efficacy and these drugs are associated with severe side effects necessitating alternatives for vascular normalization. Recently, moderate aerobic exercise has been shown to induce vascular normalization in mouse models. Here, we provide a mechanistic explanation for the tumor vascular normalization induced by exercise. Shear stress, the mechanical stimuli exerted on endothelial cells by blood flow, modulates vascular integrity. Increasing vascular shear stress through aerobic exercise can alter and remodel blood vessels in normal tissues. Our data in mouse models indicate that activation of calcineurin-NFAT-TSP1 signaling in endothelial cells plays a critical role in exercise-induced shear stress mediated tumor vessel remodeling. We show that moderate aerobic exercise with chemotherapy caused a significantly greater decrease in tumor growth than chemotherapy alone through improved chemotherapy delivery after tumor vascular normalization. Our work suggests that the vascular normalizing effects of aerobic exercise can be an effective chemotherapy adjuvant.

  20. NMR blood vessel imaging method and apparatus

    International Nuclear Information System (INIS)

    Riederer, S.J.

    1988-01-01

    A high speed method of forming computed images of blood vessels based on measurements of characteristics of a body is described comprising the steps of: subjecting a predetermined body area containing blood vessels of interest to, successively, applications of a short repetition time (TR) NMR pulse sequence during the period of high blood velocity and then to corresponding applications during the period of low blood velocity for successive heart beat cycles; weighting the collected imaging data from each application of the NMR pulse sequence according to whether the data was acquired during the period of high blood velocity or a period of low blood velocity of the corresponding heart beat cycle; accumulating weighted imaging data from a plurality of NMR pulse sequences corresponding to high blood velocity periods and from a plurality of NMR pulse sequences corresponding to low blood velocity periods; subtracting the weighted imaging data corresponding to each specific phase encoding acquired during the high blood velocity periods from the weighted imaging data for the same phase encoding corresponding to low blood velocity periods in order to compute blood vessel imaging data; and forming an image of the blood vessels of interest from the blood vessel imaging data

  1. Ionizing radiations and blood vessels

    International Nuclear Information System (INIS)

    Vorob'ev, E.I.; Stepanov, R.P.

    1985-01-01

    Data on phenomeology of radiation changes of blood vessels are systemized and the authors' experience is generalyzed. A critical analysis of modern conceptions on processes resulting in vessel structure damage after irradiation, is given. Special attention is paid to reparation and compensation of radiation injury of vessels

  2. Bone marrow blood vessels: normal and neoplastic niche

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    Saeid Shahrabi

    2016-11-01

    Full Text Available Blood vessels are among the most important factors in the transport of materials such as nutrients and oxygen. This study will review the role of blood vessels in normal bone marrow hematopoiesis as well as pathological conditions like leukemia and metastasis. Relevant literature was identified by a Pubmed search (1992-2016 of English-language papers using the terms bone marrow, leukemia, metastasis, and vessel. Given that blood vessels are conduits for the transfer of nutrients, they create a favorable situation for cancer cells and cause their growth and development. On the other hand, blood vessels protect leukemia cells against chemotherapy drugs. Finally, it may be concluded that the vessels are an important factor in the development of malignant diseases.

  3. Ionizing radiations and blood vessels

    International Nuclear Information System (INIS)

    Vorob'ev, E.I.; Stepanov, R.P.

    1985-01-01

    Data on phenomenology of radiation-induced changes in blood vessels are systematized and authors' experience is generalized. Modern concepts about processes leading to vessel structure injury after irradiation is critically analyzed. Special attention is paid to reparation and compensation of X-ray vessel injury, consideration of which is not yet sufficiently elucidated in literature

  4. Vascular targeting of LIGHT normalizes blood vessels in primary brain cancer and induces intratumoural high endothelial venules.

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    He, Bo; Jabouille, Arnaud; Steri, Veronica; Johansson-Percival, Anna; Michael, Iacovos P; Kotamraju, Venkata Ramana; Junckerstorff, Reimar; Nowak, Anna K; Hamzah, Juliana; Lee, Gabriel; Bergers, Gabriele; Ganss, Ruth

    2018-06-01

    High-grade brain cancer such as glioblastoma (GBM) remains an incurable disease. A common feature of GBM is the angiogenic vasculature, which can be targeted with selected peptides for payload delivery. We assessed the ability of micelle-tagged, vascular homing peptides RGR, CGKRK and NGR to specifically bind to blood vessels in syngeneic orthotopic GBM models. By using the peptide CGKRK to deliver the tumour necrosis factor (TNF) superfamily member LIGHT (also known as TNF superfamily member 14; TNFSF14) to angiogenic tumour vessels, we have generated a reagent that normalizes the brain cancer vasculature by inducing pericyte contractility and re-establishing endothelial barrier integrity. LIGHT-mediated vascular remodelling also activates endothelia and induces intratumoural high endothelial venules (HEVs), which are specialized blood vessels for lymphocyte infiltration. Combining CGKRK-LIGHT with anti-vascular endothelial growth factor and checkpoint blockade amplified HEV frequency and T-cell accumulation in GBM, which is often sparsely infiltrated by immune effector cells, and reduced tumour burden. Furthermore, CGKRK and RGR peptides strongly bound to blood vessels in freshly resected human GBM, demonstrating shared peptide-binding activities in mouse and human primary brain tumour vessels. Thus, peptide-mediated LIGHT targeting is a highly translatable approach in primary brain cancer to reduce vascular leakiness and enhance immunotherapy. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  5. [Stem and progenitor cells in biostructure of blood vessel walls].

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    Korta, Krzysztof; Kupczyk, Piotr; Skóra, Jan; Pupka, Artur; Zejler, Paweł; Hołysz, Marcin; Gajda, Mariusz; Nowakowska, Beata; Barć, Piotr; Dorobisz, Andrzej T; Dawiskiba, Tomasz; Szyber, Piotr; Bar, Julia

    2013-09-18

    Development of vascular and hematopoietic systems during organogenesis occurs at the same time. During vasculogenesis, a small part of cells does not undergo complete differentiation but stays on this level, "anchored" in tissue structures described as stem cell niches. The presence of blood vessels within tissue stem cell niches is typical and led to identification of niches and ensures that they are functioning. The three-layer biostructure of vessel walls for artery and vein, tunica: intima, media and adventitia, for a long time was defined as a mechanical barrier between vessel light and the local tissue environment. Recent findings from vascular biology studies indicate that vessel walls are dynamic biostructures, which are equipped with stem and progenitor cells, described as vascular wall-resident stem cells/progenitor cells (VW-SC/PC). Distinct zones for vessel wall harbor heterogeneous subpopulations of VW-SC/PC, which are described as "subendothelial or vasculogenic zones". Recent evidence from in vitro and in vivo studies show that prenatal activity of stem and progenitor cells is not only limited to organogenesis but also exists in postnatal life, where it is responsible for vessel wall homeostasis, remodeling and regeneration. It is believed that VW-SC/PC could be engaged in progression of vascular disorders and development of neointima. We would like to summarize current knowledge about mesenchymal and progenitor stem cell phenotype with special attention to distribution and biological properties of VW-SC/PC in biostructures of intima, media and adventitia niches. It is postulated that in the near future, niches for VW-SC/PC could be a good source of stem and progenitor cells, especially in the context of vessel tissue bioengineering as a new alternative to traditional revascularization therapies.

  6. Stem and progenitor cells in biostructure of blood vessel walls

    Directory of Open Access Journals (Sweden)

    Krzysztof Korta

    2013-09-01

    Full Text Available Development of vascular and hematopoietic systems during organogenesis occurs at the same time. During vasculogenesis, a small part of cells does not undergo complete differentiation but stays on this level, “anchored” in tissue structures described as stem cell niches. The presence of blood vessels within tissue stem cell niches is typical and led to identification of niches and ensures that they are functioning. The three-layer biostructure of vessel walls for artery and vein, tunica: intima, media and adventitia, for a long time was defined as a mechanical barrier between vessel light and the local tissue environment. Recent findings from vascular biology studies indicate that vessel walls are dynamic biostructures, which are equipped with stem and progenitor cells, described as vascular wall-resident stem cells/progenitor cells (VW-SC/PC. Distinct zones for vessel wall harbor heterogeneous subpopulations of VW-SC/PC, which are described as “subendothelial or vasculogenic zones”. Recent evidence from in vitro and in vivo studies show that prenatal activity of stem and progenitor cells is not only limited to organogenesis but also exists in postnatal life, where it is responsible for vessel wall homeostasis, remodeling and regeneration. It is believed that VW-SC/PC could be engaged in progression of vascular disorders and development of neointima. We would like to summarize current knowledge about mesenchymal and progenitor stem cell phenotype with special attention to distribution and biological properties of VW-SC/PC in biostructures of intima, media and adventitia niches. It is postulated that in the near future, niches for VW-SC/PC could be a good source of stem and progenitor cells, especially in the context of vessel tissue bioengineering as a new alternative to traditional revascularization therapies.

  7. Trends in Tissue Engineering for Blood Vessels

    Directory of Open Access Journals (Sweden)

    Judee Grace Nemeno-Guanzon

    2012-01-01

    Full Text Available Over the years, cardiovascular diseases continue to increase and affect not only human health but also the economic stability worldwide. The advancement in tissue engineering is contributing a lot in dealing with this immediate need of alleviating human health. Blood vessel diseases are considered as major cardiovascular health problems. Although blood vessel transplantation is the most convenient treatment, it has been delimited due to scarcity of donors and the patient’s conditions. However, tissue-engineered blood vessels are promising alternatives as mode of treatment for blood vessel defects. The purpose of this paper is to show the importance of the advancement on biofabrication technology for treatment of soft tissue defects particularly for vascular tissues. This will also provide an overview and update on the current status of tissue reconstruction especially from autologous stem cells, scaffolds, and scaffold-free cellular transplantable constructs. The discussion of this paper will be focused on the historical view of cardiovascular tissue engineering and stem cell biology. The representative studies featured in this paper are limited within the last decade in order to trace the trend and evolution of techniques for blood vessel tissue engineering.

  8. Involvement of the Reck tumor suppressor protein in maternal and embryonic vascular remodeling in mice

    Directory of Open Access Journals (Sweden)

    Kitayama Hitoshi

    2010-08-01

    Full Text Available Abstract Background Developmental angiogenesis proceeds through multiple morphogenetic events including sprouting, intussusception, and pruning. Mice lacking the membrane-anchored metalloproteinase regulator Reck die in utero around embryonic day 10.5 with halted vascular development; however, the mechanisms by which this phenotype arises remain unclear. Results We found that Reck is abundantly expressed in the cells associated with blood vessels undergoing angiogenesis or remodelling in the uteri of pregnant female mice. Some of the Reck-positive vessels show morphological features consistent with non-sprouting angiogenesis. Treatment with a vector expressing a small hairpin RNA against Reck severely disrupts the formation of blood vessels with a compact, round lumen. Similar defects were found in the vasculature of Reck-deficient or Reck conditional knockout embryos. Conclusions Our findings implicate Reck in vascular remodeling, possibly through non-sprouting angiogenesis, in both maternal and embyornic tissues.

  9. A computational model predicting disruption of blood vessel development.

    Directory of Open Access Journals (Sweden)

    Nicole Kleinstreuer

    2013-04-01

    Full Text Available Vascular development is a complex process regulated by dynamic biological networks that vary in topology and state across different tissues and developmental stages. Signals regulating de novo blood vessel formation (vasculogenesis and remodeling (angiogenesis come from a variety of biological pathways linked to endothelial cell (EC behavior, extracellular matrix (ECM remodeling and the local generation of chemokines and growth factors. Simulating these interactions at a systems level requires sufficient biological detail about the relevant molecular pathways and associated cellular behaviors, and tractable computational models that offset mathematical and biological complexity. Here, we describe a novel multicellular agent-based model of vasculogenesis using the CompuCell3D (http://www.compucell3d.org/ modeling environment supplemented with semi-automatic knowledgebase creation. The model incorporates vascular endothelial growth factor signals, pro- and anti-angiogenic inflammatory chemokine signals, and the plasminogen activating system of enzymes and proteases linked to ECM interactions, to simulate nascent EC organization, growth and remodeling. The model was shown to recapitulate stereotypical capillary plexus formation and structural emergence of non-coded cellular behaviors, such as a heterologous bridging phenomenon linking endothelial tip cells together during formation of polygonal endothelial cords. Molecular targets in the computational model were mapped to signatures of vascular disruption derived from in vitro chemical profiling using the EPA's ToxCast high-throughput screening (HTS dataset. Simulating the HTS data with the cell-agent based model of vascular development predicted adverse effects of a reference anti-angiogenic thalidomide analog, 5HPP-33, on in vitro angiogenesis with respect to both concentration-response and morphological consequences. These findings support the utility of cell agent-based models for simulating a

  10. Distinct bone marrow blood vessels differentially regulate haematopoiesis.

    Science.gov (United States)

    Itkin, Tomer; Gur-Cohen, Shiri; Spencer, Joel A; Schajnovitz, Amir; Ramasamy, Saravana K; Kusumbe, Anjali P; Ledergor, Guy; Jung, Yookyung; Milo, Idan; Poulos, Michael G; Kalinkovich, Alexander; Ludin, Aya; Kollet, Orit; Shakhar, Guy; Butler, Jason M; Rafii, Shahin; Adams, Ralf H; Scadden, David T; Lin, Charles P; Lapidot, Tsvee

    2016-04-21

    Bone marrow endothelial cells (BMECs) form a network of blood vessels that regulate both leukocyte trafficking and haematopoietic stem and progenitor cell (HSPC) maintenance. However, it is not clear how BMECs balance these dual roles, and whether these events occur at the same vascular site. We found that mammalian bone marrow stem cell maintenance and leukocyte trafficking are regulated by distinct blood vessel types with different permeability properties. Less permeable arterial blood vessels maintain haematopoietic stem cells in a low reactive oxygen species (ROS) state, whereas the more permeable sinusoids promote HSPC activation and are the exclusive site for immature and mature leukocyte trafficking to and from the bone marrow. A functional consequence of high permeability of blood vessels is that exposure to blood plasma increases bone marrow HSPC ROS levels, augmenting their migration and differentiation, while compromising their long-term repopulation and survival. These findings may have relevance for clinical haematopoietic stem cell transplantation and mobilization protocols.

  11. Automatic segmentation of blood vessels from retinal fundus images ...

    Indian Academy of Sciences (India)

    The retinal blood vessels were segmented through color space conversion and color channel .... Retinal blood vessel segmentation was also attempted through multi-scale operators. A few works in this ... fundus camera at 35 degrees field of view. The image ... vessel segmentation is available from two human observers.

  12. Functional dilatation and medial remodeling of the renal artery in response to chronic increased blood flow.

    Science.gov (United States)

    Roan, Jun-Neng; Yeh, Chin-Yi; Chiu, Wen-Cheng; Lee, Chou-Hwei; Chang, Shih-Wei; Jiangshieh, Ya-Fen; Tsai, Yu-Chuan; Lam, Chen-Fuh

    2011-01-01

    Renal blood flow (RBF) is tightly regulated by several intrinsic pathways in maintaining optimal kidney blood supply. Using a rat model of aortocaval (AC) fistula, we investigated remodeling of the renal artery following prolonged increased blood flow. An AC fistula was created in the infrarenal aorta of anesthetized rats, and changes of blood flow in the renal artery were assessed using an ultrasonic flow probe. Morphological changes and expression of endothelial nitric oxide synthase and matrix metalloproteinase-2 in the remodeled renal artery were analyzed. Blood flow in the renal artery increased immediately after creation of AC fistula, but normal RBF was restored 8 weeks later. The renal artery dilated significantly 8 weeks after operation. Expression of endothelial nitric oxide synthase and matrix metalloproteinase-2 was upregulated shortly after blood flow increase, and returned to baseline levels after 3 weeks. Histological sections showed luminal dilatation with medial thickening and endothelial cell-to-smooth muscle cell attachments in the remodeled renal artery. Increased RBF was accommodated by functional dilatation and remodeling in the medial layer of the renal artery in order to restore normal blood flow. Our results provide important mechanistic insight into the intrinsic regulation of the renal artery in response to increased RBF. Copyright © 2011 S. Karger AG, Basel.

  13. Evaluation of Aortic Blood Flow and Wall Shear Stress in Aortic Stenosis and Its Association With Left Ventricular Remodeling

    Science.gov (United States)

    von Knobelsdorff-Brenkenhoff, Florian; Karunaharamoorthy, Achudhan; Trauzeddel, Ralf Felix; Barker, Alex J; Blaszczyk, Edyta; Markl, Michael; Schulz-Menger, Jeanette

    2016-01-01

    Background Aortic stenosis (AS) leads to variable stress for the left ventricle (LV) and consequently a broad range of LV remodeling. Study aim was to describe blood flow patterns in the ascending aorta of AS patients and determine their association with remodeling. Methods and Results Thirty-seven patients with AS (14 mild, 8 moderate, 15 severe; age 63±13 years) and 37 healthy controls (age 60±10 years) underwent 4D-flow MRI. Helical and vortical flow formations and flow eccentricity were assessed in the ascending aorta. Normalized flow displacement from the vessel center and peak systolic wall shear stress (WSSpeak) in the ascending aorta were quantified. LV remodeling was assessed based on LV mass index (LVMI-I) and the ratio of LV mass to enddiastolic volume (relative wall mass; RWM). Marked helical and vortical flow formation and eccentricity were more prevalent in patients with AS than in healthy subjects, and AS patients exhibited an asymmetric and elevated distribution of WSSpeak. In AS, aortic orifice area was strongly negatively associated with vortical flow formation (p=0.0274), eccentricity (p=0.0070) and flow displacement (p=0.0021). Bicuspid aortic valve was associated with more intense helical (p=0.0098) and vortical flow formation (p=0.0536), higher flow displacement (p=0.11) and higher WSSpeak (p=0.0926). LVM-I and RWM were significantly associated with aortic orifice area (p=0.0611, p=0.0058) and flow displacement (p=0.0058, p=0.0283). Conclusions In this pilot study, AS leads to abnormal blood flow pattern and WSSpeak in the ascending aorta. In addition to aortic orifice area, normalized flow displacement was significantly associated with LV remodeling. PMID:26917824

  14. New aspects of vascular remodelling: the involvement of all vascular cell types.

    Science.gov (United States)

    McGrath, John C; Deighan, Clare; Briones, Ana M; Shafaroudi, Majid Malekzadeh; McBride, Melissa; Adler, Jeremy; Arribas, Silvia M; Vila, Elisabet; Daly, Craig J

    2005-07-01

    Conventionally, the architecture of arteries is based around the close-packed smooth muscle cells and extracellular matrix. However, the adventitia and endothelium are now viewed as key players in vascular growth and repair. A new dynamic picture has emerged of blood vessels in a constant state of self-maintenance. Recent work raises fundamental questions about the cellular heterogeneity of arteries and the time course and triggering of normal and pathological remodelling. A common denominator emerging in hypertensive remodelling is an early increase in adventitial cell density suggesting that adventitial cells drive remodelling and may initiate subsequent changes such as re-arrangement of smooth muscle cells and extracellular matrix. The organization of vascular smooth muscle cells follows regular arrangements that can be modelled mathematically. In hypertension, new patterns can be quantified in these terms and give insights to how structure affects function. As with smooth muscle, little is known about the organization of the vascular endothelium, or its role in vascular remodelling. Current observations suggest that there may be a close relationship between the helical organization of smooth muscle cells and the underlying pattern of endothelial cells. The function of myoendothelial connections is a topic of great current interest and may relate to the structure of the internal elastic lamina through which the connections must pass. In hypertensive remodelling this must present an organizational challenge. The objective of this paper is to show how the functions of blood vessels depend on their architecture and a continuous interaction of different cell types and extracellular proteins.

  15. Recovery of testicular blood flow following ligation of testicular vessels

    International Nuclear Information System (INIS)

    Pascual, J.A.; Villanueva-Meyer, J.; Salido, E.; Ehrlich, R.M.; Mena, I.; Rajfer, J.

    1989-01-01

    To determine whether initial ligation of the testicular vessels of the high undescended testis followed by a delayed secondary orchiopexy is a viable alternative to the classical Fowler-Stephens procedure, a series of preliminary experiments were conducted in the rat in which testicular blood flow was measured by the 133-xenon washout technique before, and 1 hour and 30 days after ligation of the vessels. In addition, testicular histology, and testis and sex-accessory tissue weights were measured in 6 control, 6 sham operated and 6 testicular vessel ligated rats 54 days after vessel ligation. The data demonstrate that ligation and division of the testicular blood vessels produce an 80 per cent decrease in testicular blood flow 1 hour after ligation of the vessels. However, 30 days later testis blood flow returns to the control and pre-treatment value. There were no significant changes in testis or sex-accessory tissue weights 54 days after vessel ligation. Histologically, 4 of the surgically operated testes demonstrated necrosis of less than 25 per cent of the seminiferous tubules while 1 testis demonstrated more than 75 per cent necrosis. The rest of the tubules in all 6 testes demonstrated normal spermatogenesis. From this study we conclude that initial testicular vessel ligation produces an immediate decrease in testicular blood flow but with time the collateral vessels are able to compensate and return the testis blood flow to its normal pre-treatment value. These preliminary observations lend support for the concept that initial ligation of the testicular vessels followed by a delayed secondary orchiopexy in patients with a high undescended testis may be a possible alternative to the classical Fowler-Stephens approach

  16. Application of morphological bit planes in retinal blood vessel extraction.

    Science.gov (United States)

    Fraz, M M; Basit, A; Barman, S A

    2013-04-01

    The appearance of the retinal blood vessels is an important diagnostic indicator of various clinical disorders of the eye and the body. Retinal blood vessels have been shown to provide evidence in terms of change in diameter, branching angles, or tortuosity, as a result of ophthalmic disease. This paper reports the development for an automated method for segmentation of blood vessels in retinal images. A unique combination of methods for retinal blood vessel skeleton detection and multidirectional morphological bit plane slicing is presented to extract the blood vessels from the color retinal images. The skeleton of main vessels is extracted by the application of directional differential operators and then evaluation of combination of derivative signs and average derivative values. Mathematical morphology has been materialized as a proficient technique for quantifying the retinal vasculature in ocular fundus images. A multidirectional top-hat operator with rotating structuring elements is used to emphasize the vessels in a particular direction, and information is extracted using bit plane slicing. An iterative region growing method is applied to integrate the main skeleton and the images resulting from bit plane slicing of vessel direction-dependent morphological filters. The approach is tested on two publicly available databases DRIVE and STARE. Average accuracy achieved by the proposed method is 0.9423 for both the databases with significant values of sensitivity and specificity also; the algorithm outperforms the second human observer in terms of precision of segmented vessel tree.

  17. Fluid and mass transport in a single lymphatic blood vessel

    International Nuclear Information System (INIS)

    Bestman, A.R.

    1987-08-01

    The problem considers the single blood vessel model in pulmonary circulation in the presence of gravitation and mass transfer. The tissue surrounding the blood vessel is modelled as a permeable medium distinct from the blood vessel which is a normal free space. On the assumption that the mass concentration varies slowly at the interface between the blood vessel and the tissue, the problem is tackled by asymptotic approximation. A crucial point of the analysis is the dependence of the flow variables on the permeability K of the tissue in a completely arbitrary manner. A primary conjecture of the study is the intimacy of the pathological pulmonary edema and the parameter K. (author). 4 refs

  18. Margination of Stiffened Red Blood Cells Regulated By Vessel Geometry.

    Science.gov (United States)

    Chen, Yuanyuan; Li, Donghai; Li, Yongjian; Wan, Jiandi; Li, Jiang; Chen, Haosheng

    2017-11-10

    Margination of stiffened red blood cells has been implicated in many vascular diseases. Here, we report the margination of stiffened RBCs in vivo, and reveal the crucial role of the vessel geometry in the margination by calculations when the blood is seen as viscoelastic fluid. The vessel-geometry-regulated margination is then confirmed by in vitro experiments in microfluidic devices, and it establishes new insights to cell sorting technology and artificial blood vessel fabrication.

  19. Immersive volume rendering of blood vessels

    Science.gov (United States)

    Long, Gregory; Kim, Han Suk; Marsden, Alison; Bazilevs, Yuri; Schulze, Jürgen P.

    2012-03-01

    In this paper, we present a novel method of visualizing flow in blood vessels. Our approach reads unstructured tetrahedral data, resamples it, and uses slice based 3D texture volume rendering. Due to the sparse structure of blood vessels, we utilize an octree to efficiently store the resampled data by discarding empty regions of the volume. We use animation to convey time series data, wireframe surface to give structure, and utilize the StarCAVE, a 3D virtual reality environment, to add a fully immersive element to the visualization. Our tool has great value in interdisciplinary work, helping scientists collaborate with clinicians, by improving the understanding of blood flow simulations. Full immersion in the flow field allows for a more intuitive understanding of the flow phenomena, and can be a great help to medical experts for treatment planning.

  20. Interstitial Cells of Blood Vessels

    Directory of Open Access Journals (Sweden)

    Vladimír Pucovský

    2010-01-01

    Full Text Available Blood vessels are made up of several distinct cell types. Although it was originally thought that the tunica media of blood vessels was composed of a homogeneous population of fully differentiated smooth muscle cells, more recent data suggest the existence of multiple smooth muscle cell subpopulations in the vascular wall. One of the cell types contributing to this heterogeneity is the novel, irregularly shaped, noncontractile cell with thin processes, termed interstitial cell, found in the tunica media of both veins and arteries. While the principal role of interstitial cells in veins seems to be pacemaking, the role of arterial interstitial cells is less clear. This review summarises the knowledge of the functional and structural properties of vascular interstitial cells accumulated so far, offers hypotheses on their physiological role, and proposes directions for future research.

  1. Depiction of blood vessels by x-ray phase contrast

    Energy Technology Data Exchange (ETDEWEB)

    Momose, Atsushi [School of Engineering, University of Tokyo, Tokyo (Japan); Takeda, Tohoru; Itai, Yuji [Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki (Japan)

    2001-04-01

    Blood vessels in livers of a mouse and a rat were depicted by phase-contrast x-ray imaging with an x-ray interferometer without using contrast agents. X-ray interference patterns were converted to image mapping x-ray phase shift caused by the livers using the technique of phase-shifting x-ray interferometry. The arteries and veins to and from the livers were tied before excision in order to prevent blood from flowing out of the liver. The x-ray phase shift caused by blood was substantially different from that caused by other soft sues, and consequently trees of blood vessels were revealed in the images. Vessels of diameter smaller than 0.1 mm were detected. This result suggests new possibilities for investigating vascular systems. (author)

  2. Effects of aging and resistance training in rat tendon remodeling.

    Science.gov (United States)

    Marqueti, Rita C; Durigan, João L Q; Oliveira, Anderson José S; Mekaro, Marcelo Shinyu; Guzzoni, Vinicius; Aro, Andrea A; Pimentel, Edson Rosa; Selistre-de-Araujo, Heloisa S

    2018-01-01

    In elderly persons, weak tendons contribute to functional limitations, injuries, and disability, but resistance training can attenuate this age-related decline. We evaluated the effects of resistance training on the extracellular matrix (ECM) of the calcaneal tendon (CT) in young and old rats and its effect on tendon remodeling. Wistar rats aged 3 mo (young, n = 30) and 20 mo (old, n = 30) were divided into 4 groups: young sedentary, young trained, old sedentary (OS), and old trained (OT). The training sessions were conducted over a 12-wk period. Aging in sedentary rats showed down-regulation in key genes that regulated ECM remodeling. Moreover, the OS group showed a calcification focus in the distal region of the CT, with reduced blood vessel volume density. In contrast, resistance training was effective in up-regulating connective tissue growth factor, VEGF, and decorin gene expression in old rats. Resistance training also increased proteoglycan content in young and old rats in special small leucine-rich proteoglycans and blood vessels and prevented calcification in OT rats. These findings confirm that resistance training is a potential mechanism in the prevention of aging-related loss in ECM and that it attenuates the detrimental effects of aging in tendons, such as ruptures and tendinopathies.-Marqueti, R. C., Durigan, J. L. Q., Oliveira, A. J. S., Mekaro, M. S., Guzzoni, V., Aro, A. A., Pimentel, E. R., Selistre-de-Araujo, H. S. Effects of aging and resistance training in rat tendon remodeling. © FASEB.

  3. “Data characterizing microfabricated human blood vessels created via hydrodynamic focusing”

    Directory of Open Access Journals (Sweden)

    Kyle A. DiVito

    2017-10-01

    Full Text Available This data article provides further detailed information related to our research article titled “Microfabricated Blood Vessels Undergo Neovascularization” (DiVito et al., 2017 [1], in which we report fabrication of human blood vessels using hydrodynamic focusing (HDF. Hydrodynamic focusing with advection inducing chevrons were used in concert to encase one fluid stream within another, shaping the inner core fluid into ‘bullseye-like” cross-sections that were preserved through click photochemistry producing streams of cellularized hollow 3-dimensional assemblies, such as human blood vessels (Daniele et al., 2015a, 2015b, 2014, 2016; Roberts et al., 2016 [2–6]. Applications for fabricated blood vessels span general tissue engineering to organ-on-chip technologies, with specific utility in in vitro drug delivery and pharmacodynamics studies. Here, we report data regarding the construction of blood vessels including cellular composition and cell positioning within the engineered vascular construct as well as functional aspects of the tissues.

  4. Correlation between genetic polymorphism of matrix metalloproteinase-9 in patients with coronary artery disease and cardiac remodeling.

    Science.gov (United States)

    Yu, Qibin; Li, Hanmei; Li, Linlin; Wang, Shaoye; Wu, Yongbo

    2015-01-01

    To explore the correlation between genetic polymorphism of matrix metalloproteinase-9 (MMP-9) in patients with coronary artery disease (CAD) and cardiac remodeling. A total of 272 subjects who received coronary angiography in our hospital from July 2008 to September 2013 were selected, including 172 CAD patients (CAD group) and another 100 ones (control group). Both groups were subjected to MMP-9 and ultrasonic detections to determine vascular remodeling and atherosclerotic plaques. C1562G polymorphism of MMP-9 gene was detected, and correlation with vascular remodeling and atherosclerotic plaque was analyzed. Serum MMP-9 level of CAD group (330.87±50.39 ng/ml) was significantly higher than that of control group (134.87±34.02 ng/ml) (P<0.05). Compared with control group, CAD group had significantly higher intima-media thickness, and significantly lower systolic peak velocity, mean systolic velocity and end-diastolic velocity (P<0.05). Total area of stenotic blood vessels was 67.34±22.98 mm(2), while that of control blood vessels was 64.00±20.83 mm(2). G/G, G/C and C/C genotype frequencies of MMP-9 differed significantly in the two groups (P<0.05). G and C allele frequencies of CAD group (70.9% and 29.1%) were significantly different from those of control group (50.0% and 50.0%) (P<0.05). G/G, G/C and C/C genotypes were manifested as lipid-rich, fibrous and calcified or ulcerated plaques respectively. Total area of stenotic blood vessels of G/G genotype significantly exceeded those of G/C and C/C genotypes (P<0.05), whereas the latter two had no significant differences. CAD promoted 1562C-G transformation of MMP-9 gene into genetic polymorphism, thus facilitating arterial remodeling and increasing unstable atherosclerotic plaques.

  5. Acrolein generation stimulates hypercontraction in isolated human blood vessels

    International Nuclear Information System (INIS)

    Conklin, D.J.; Bhatnagar, A.; Cowley, H.R.; Johnson, G.H.; Wiechmann, R.J.; Sayre, L.M.; Trent, M.B.; Boor, P.J.

    2006-01-01

    Increased risk of vasospasm, a spontaneous hyperconstriction, is associated with atherosclerosis, cigarette smoking, and hypertension-all conditions involving oxidative stress, lipid peroxidation, and inflammation. To test the role of the lipid peroxidation- and inflammation-derived aldehyde, acrolein, in human vasospasm, we developed an ex vivo model using human coronary artery bypass graft (CABG) blood vessels and a demonstrated acrolein precursor, allylamine. Allylamine induces hypercontraction in isolated rat coronary artery in a semicarbazide-sensitive amine oxidase activity (SSAO) dependent manner. Isolated human CABG blood vessels (internal mammary artery, radial artery, saphenous vein) were used to determine: (1) vessel responses and sensitivity to acrolein, allylamine, and H 2 O 2 exposure (1 μM-1 mM), (2) SSAO dependence of allylamine-induced effects using SSAO inhibitors (semicarbazide, 1 mM; MDL 72274-E, active isomer; MDL 72274-Z, inactive isomer; 100 μM), (3) the vasoactive effects of two other SSAO amine substrates, benzylamine and methylamine, and (4) the contribution of extracellular Ca 2+ to hypercontraction. Acrolein or allylamine but not H 2 O 2 , benzylamine, or methylamine stimulated spontaneous and pharmacologically intractable hypercontraction in CABG blood vessels that was similar to clinical vasospasm. Allylamine-induced hypercontraction and blood vessel SSAO activity were abolished by pretreatment with semicarbazide or MDL 72274-E but not by MDL 72274-Z. Allylamine-induced hypercontraction also was significantly attenuated in Ca 2+ -free buffer. In isolated aorta of spontaneously hypertensive rat, allylamine-induced an SSAO-dependent contraction and enhanced norepinephrine sensitivity but not in Sprague-Dawley rat aorta. We conclude that acrolein generation in the blood vessel wall increases human susceptibility to vasospasm, an event that is enhanced in hypertension

  6. Captopril improves tumor nanomedicine delivery by increasing tumor blood perfusion and enlarging endothelial gaps in tumor blood vessels.

    Science.gov (United States)

    Zhang, Bo; Jiang, Ting; Tuo, Yanyan; Jin, Kai; Luo, Zimiao; Shi, Wei; Mei, Heng; Hu, Yu; Pang, Zhiqing; Jiang, Xinguo

    2017-12-01

    Poor tumor perfusion and unfavorable vessel permeability compromise nanomedicine drug delivery to tumors. Captopril dilates blood vessels, reducing blood pressure clinically and bradykinin, as the downstream signaling moiety of captopril, is capable of dilating blood vessels and effectively increasing vessel permeability. The hypothesis behind this study was that captopril can dilate tumor blood vessels, improving tumor perfusion and simultaneously enlarge the endothelial gaps of tumor vessels, therefore enhancing nanomedicine drug delivery for tumor therapy. Using the U87 tumor xenograft with abundant blood vessels as the tumor model, tumor perfusion experiments were carried out using laser Doppler imaging and lectin-labeling experiments. A single treatment of captopril at a dose of 100 mg/kg significantly increased the percentage of functional vessels in tumor tissues and improved tumor blood perfusion. Scanning electron microscopy of tumor vessels also indicated that the endothelial gaps of tumor vessels were enlarged after captopril treatment. Immunofluorescence-staining of tumor slices demonstrated that captopril significantly increased bradykinin expression, possibly explaining tumor perfusion improvements and endothelial gap enlargement. Additionally, imaging in vivo, imaging ex vivo and nanoparticle distribution in tumor slices indicated that after a single treatment with captopril, the accumulation of 115-nm nanoparticles in tumors had increased 2.81-fold with a more homogeneous distribution pattern in comparison to non-captopril treated controls. Finally, pharmacodynamics experiments demonstrated that captopril combined with paclitaxel-loaded nanoparticles resulted in the greatest tumor shrinkage and the most extensive necrosis in tumor tissues among all treatment groups. Taken together, the data from the present study suggest a novel strategy for improving tumor perfusion and enlarging blood vessel permeability simultaneously in order to improve

  7. Blood Vessels in Allotransplantation.

    Science.gov (United States)

    Abrahimi, P; Liu, R; Pober, J S

    2015-07-01

    Human vascularized allografts are perfused through blood vessels composed of cells (endothelium, pericytes, and smooth muscle cells) that remain largely of graft origin and are thus subject to host alloimmune responses. Graft vessels must be healthy to maintain homeostatic functions including control of perfusion, maintenance of permselectivity, prevention of thrombosis, and participation in immune surveillance. Vascular cell injury can cause dysfunction that interferes with these processes. Graft vascular cells can be activated by mediators of innate and adaptive immunity to participate in graft inflammation contributing to both ischemia/reperfusion injury and allograft rejection. Different forms of rejection may affect graft vessels in different ways, ranging from thrombosis and neutrophilic inflammation in hyperacute rejection, to endothelialitis/intimal arteritis and fibrinoid necrosis in acute cell-mediated or antibody-mediated rejection, respectively, and to diffuse luminal stenosis in chronic rejection. While some current therapies targeting the host immune system do affect graft vascular cells, direct targeting of the graft vasculature may create new opportunities for preventing allograft injury and loss. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  8. Predictive simulation of bidirectional Glenn shunt using a hybrid blood vessel model.

    Science.gov (United States)

    Li, Hao; Leow, Wee Kheng; Chiu, Ing-Sh

    2009-01-01

    This paper proposes a method for performing predictive simulation of cardiac surgery. It applies a hybrid approach to model the deformation of blood vessels. The hybrid blood vessel model consists of a reference Cosserat rod and a surface mesh. The reference Cosserat rod models the blood vessel's global bending, stretching, twisting and shearing in a physically correct manner, and the surface mesh models the surface details of the blood vessel. In this way, the deformation of blood vessels can be computed efficiently and accurately. Our predictive simulation system can produce complex surgical results given a small amount of user inputs. It allows the surgeon to easily explore various surgical options and evaluate them. Tests of the system using bidirectional Glenn shunt (BDG) as an application example show that the results produc by the system are similar to real surgical results.

  9. Three-dimensional imaging of absolute blood flow velocity and blood vessel position under low blood flow velocity based on Doppler signal information included in scattered light from red blood cells

    Science.gov (United States)

    Kyoden, Tomoaki; Akiguchi, Shunsuke; Tajiri, Tomoki; Andoh, Tsugunobu; Hachiga, Tadashi

    2017-11-01

    The development of a system for in vivo visualization of occluded distal blood vessels for diabetic patients is the main target of our research. We herein describe two-beam multipoint laser Doppler velocimetry (MLDV), which measures the instantaneous multipoint flow velocity and can be used to observe the blood flow velocity in peripheral blood vessels. By including a motorized stage to shift the measurement points horizontally and in the depth direction while measuring the velocity, the path of the blood vessel in the skin could be observed using blood flow velocity in three-dimensional space. The relationship of the signal power density between the blood vessel and the surrounding tissues was shown and helped us identify the position of the blood vessel. Two-beam MLDV can be used to simultaneously determine the absolute blood flow velocity distribution and identify the blood vessel position in skin.

  10. Gene expression analysis in human breast cancer associated blood vessels.

    Directory of Open Access Journals (Sweden)

    Dylan T Jones

    Full Text Available Angiogenesis is essential for solid tumour growth, whilst the molecular profiles of tumour blood vessels have been reported to be different between cancer types. Although presently available anti-angiogenic strategies are providing some promise for the treatment of some cancers it is perhaps not surprisingly that, none of the anti-angiogenic agents available work on all tumours. Thus, the discovery of novel anti-angiogenic targets, relevant to individual cancer types, is required. Using Affymetrix microarray analysis of laser-captured, CD31-positive blood vessels we have identified 63 genes that are upregulated significantly (5-72 fold in angiogenic blood vessels associated with human invasive ductal carcinoma (IDC of the breast as compared with blood vessels in normal human breast. We tested the angiogenic capacity of a subset of these genes. Genes were selected based on either their known cellular functions, their enriched expression in endothelial cells and/or their sensitivity to anti-VEGF treatment; all features implicating their involvement in angiogenesis. For example, RRM2, a ribonucleotide reductase involved in DNA synthesis, was upregulated 32-fold in IDC-associated blood vessels; ATF1, a nuclear activating transcription factor involved in cellular growth and survival was upregulated 23-fold in IDC-associated blood vessels and HEX-B, a hexosaminidase involved in the breakdown of GM2 gangliosides, was upregulated 8-fold in IDC-associated blood vessels. Furthermore, in silico analysis confirmed that AFT1 and HEX-B also were enriched in endothelial cells when compared with non-endothelial cells. None of these genes have been reported previously to be involved in neovascularisation. However, our data establish that siRNA depletion of Rrm2, Atf1 or Hex-B had significant anti-angiogenic effects in VEGF-stimulated ex vivo mouse aortic ring assays. Overall, our results provide proof-of-principle that our approach can identify a cohort of

  11. Engineering of blood vessel patterns by angio-morphogens [angiotropins]: non-mitogenic copper-ribonucleoprotein cytokins [CuRNP ribokines] with their metalloregulated constituents of RAGE-binding S100-EF-hand proteins and extracellular RNA bioaptamers in vascular remodeling of tissue and angiogenesis in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Wissler, J.H. [ARCONS Applied Research, Bad Nauheim (Germany)

    2001-12-01

    Tissue vascularization is requisite to successful cell-based therapies, biomaterial design and implant integration. Thus, known problems in ossointegration of avascular implants in connection with the generation of bone tissue reflect arrays of general problems of socio-economic relevance existing in reparative medicine still waiting for to be solved. For this purpose, morphogenesis and remodeling of endothelial angio-architectures in tissue and in vitro by isolated non-mitogenic angio-morphogens [angiotropins] are considered in terms of their structure, function and action mechanisms. Extracellular angiotropins are secreted by activated leukocytes/monocytes/macrophages. They are a family of cytokines with morphogen bioactivity selectively directed to endothelial cells. Their structure was deciphered as metalloregulated copper-ribonucleoproteins [CuRNP ribokines]. They are built up of angiotropin-related S100-EF-hand protein [ARP] and highly modified and edited 5'end-phosphorylated RNA [ARNA], complexed together by copper ions. Oxidant-sensitive ARNA and their precursors represent novel types in a RNA world: They are the first isolated and sequenced forms of extracellular RNA [eRNA], may act as cytokine and bioaptamer, contain isoguanosine [crotonoside] as modified nucleoside and show up copper as RNA-structuring transition metal ion. By metalloregulated bioaptamer functions, ARNA impart novel biofunctions to RAGE-binding S100-EF-hand proteins. Angiotropin morphogens were shown suitable for neointiation and remodeling of blood vessel patterns in different, adult, embryonal and artificial tissues. These neovascular patterns manifest regulated hemodynamics for preventing tissue necrosis, supporting tissue functions and promoting wound healing. As evaluated in skin and muscle vascularization, the neovascular patterns are integrated into homeostatic control mechanisms of tissue. Thus, the morphogens show up beneficial perspectives and are suggested useful tools

  12. Laparoscopic prototype for optical sealing of renal blood vessels

    Science.gov (United States)

    Hardy, Luke A.; Hutchens, Thomas C.; Larson, Eric R.; Gonzalez, David A.; Chang, Chun-Hung; Nau, William H.; Fried, Nathaniel M.

    2017-02-01

    Energy-based, radiofrequency and ultrasonic devices provide rapid sealing of blood vessels during laparoscopic procedures. We are exploring infrared lasers as an alternative for vessel sealing with less collateral thermal damage. Previous studies demonstrated vessel sealing in an in vivo porcine model using a 1470-nm laser. However, the initial prototype was designed for open surgery and featured tissue clasping and light delivery mechanisms incompatible with laparoscopic surgery. In this study, a laparoscopic prototype similar to devices in surgical use was developed, and tests were conducted on porcine renal blood vessels. The 5-mm-OD prototype featured a traditional Maryland jaw configuration. Laser energy was delivered through a 550-μm-core fiber and side-delivery from the lower jaw, with beam dimensions of 18-mm-length x 1.2-mm-width. The 1470-nm diode laser delivered 68 W with 3 s activation time. A total of 69 porcine renal vessels with mean diameter of 3.3 +/- 1.7 mm were tested, ex vivo. Vessels smaller than 5 mm were consistently sealed (48/51) with burst pressures greater than malignant hypertension blood pressure (180 mmHg), averaging 1038 +/- 474 mmHg. Vessels larger than 5 mm were not consistently sealed (6/18), yielding burst pressures of only 174 +/- 221 mmHg. Seal width, thermal damage zone, and thermal spread averaged 1.7 +/- 0.8, 3.4 +/- 0.7, and 1.0 +/- 0.4 mm. A novel optical laparoscopic prototype with 5-mm- OD shaft integrated within a standard Maryland jaw design consistently sealed vessels less than 5 mm with minimal thermal spread. Further in vivo studies are planned to test performance across a variety of vessels and tissues.

  13. Vessel Sampling and Blood Flow Velocity Distribution With Vessel Diameter for Characterizing the Human Bulbar Conjunctival Microvasculature.

    Science.gov (United States)

    Wang, Liang; Yuan, Jin; Jiang, Hong; Yan, Wentao; Cintrón-Colón, Hector R; Perez, Victor L; DeBuc, Delia C; Feuer, William J; Wang, Jianhua

    2016-03-01

    This study determined (1) how many vessels (i.e., the vessel sampling) are needed to reliably characterize the bulbar conjunctival microvasculature and (2) if characteristic information can be obtained from the distribution histogram of the blood flow velocity and vessel diameter. Functional slitlamp biomicroscope was used to image hundreds of venules per subject. The bulbar conjunctiva in five healthy human subjects was imaged on six different locations in the temporal bulbar conjunctiva. The histograms of the diameter and velocity were plotted to examine whether the distribution was normal. Standard errors were calculated from the standard deviation and vessel sample size. The ratio of the standard error of the mean over the population mean was used to determine the sample size cutoff. The velocity was plotted as a function of the vessel diameter to display the distribution of the diameter and velocity. The results showed that the sampling size was approximately 15 vessels, which generated a standard error equivalent to 15% of the population mean from the total vessel population. The distributions of the diameter and velocity were not only unimodal, but also somewhat positively skewed and not normal. The blood flow velocity was related to the vessel diameter (r=0.23, Psampling size of the vessels and the distribution histogram of the blood flow velocity and vessel diameter, which may lead to a better understanding of the human microvascular system of the bulbar conjunctiva.

  14. Heritability of retinal vessel diameters and blood pressure

    DEFF Research Database (Denmark)

    Taarnhøj, Nina C B B; Larsen, Michael; Sander, Birgit

    2006-01-01

    PURPOSE: To assess the relative influence of genetic and environmental effects on retinal vessel diameters and blood pressure in healthy adults, as well as the possible genetic connection between these two characteristics. METHODS: In 55 monozygotic and 50 dizygotic same-sex healthy twin pairs......%-80%) for CRAE, 83% (95% CI: 73%-89%) for CRVE, and 61% (95% CI: 44%-73%) for mean arterial blood pressure (MABP). Retinal artery diameter decreased with increasing age and increasing arterial blood pressure. Mean vessel diameters in the population were 165.8 +/- 14.9 microm for CRAE, 246.2 +/- 17.7 microm...... for CRVE, and 0.67 +/- 0.05 microm for AVR. No significant influence on artery or vein diameters was found for gender, smoking, body mass index (BMI), total cholesterol, fasting blood glucose, or 2-hour oral glucose tolerance test values. CONCLUSIONS: In healthy young adults with normal blood pressure...

  15. Improvement of retinal blood vessel detection by spur removal and Gaussian matched filtering compensation

    Science.gov (United States)

    Xiao, Di; Vignarajan, Janardhan; An, Dong; Tay-Kearney, Mei-Ling; Kanagasingam, Yogi

    2016-03-01

    Retinal photography is a non-invasive and well-accepted clinical diagnosis of ocular diseases. Qualitative and quantitative assessment of retinal images is crucial in ocular diseases related clinical application. In this paper, we proposed approaches for improving the quality of blood vessel detection based on our initial blood vessel detection methods. A blood vessel spur pruning method has been developed for removing the blood vessel spurs both on vessel medial lines and binary vessel masks, which are caused by artifacts and side-effect of Gaussian matched vessel enhancement. A Gaussian matched filtering compensation method has been developed for removing incorrect vessel branches in the areas of low illumination. The proposed approaches were applied and tested on the color fundus images from one publicly available database and our diabetic retinopathy screening dataset. A preliminary result has demonstrated the robustness and good performance of the proposed approaches and their potential application for improving retinal blood vessel detection.

  16. Dynamic stroma reorganization drives blood vessel dysmorphia during glioma growth.

    Science.gov (United States)

    Mathivet, Thomas; Bouleti, Claire; Van Woensel, Matthias; Stanchi, Fabio; Verschuere, Tina; Phng, Li-Kun; Dejaegher, Joost; Balcer, Marly; Matsumoto, Ken; Georgieva, Petya B; Belmans, Jochen; Sciot, Raf; Stockmann, Christian; Mazzone, Massimiliano; De Vleeschouwer, Steven; Gerhardt, Holger

    2017-12-01

    Glioma growth and progression are characterized by abundant development of blood vessels that are highly aberrant and poorly functional, with detrimental consequences for drug delivery efficacy. The mechanisms driving this vessel dysmorphia during tumor progression are poorly understood. Using longitudinal intravital imaging in a mouse glioma model, we identify that dynamic sprouting and functional morphogenesis of a highly branched vessel network characterize the initial tumor growth, dramatically changing to vessel expansion, leakage, and loss of branching complexity in the later stages. This vascular phenotype transition was accompanied by recruitment of predominantly pro-inflammatory M1-like macrophages in the early stages, followed by in situ repolarization to M2-like macrophages, which produced VEGF-A and relocate to perivascular areas. A similar enrichment and perivascular accumulation of M2 versus M1 macrophages correlated with vessel dilation and malignancy in human glioma samples of different WHO malignancy grade. Targeting macrophages using anti-CSF1 treatment restored normal blood vessel patterning and function. Combination treatment with chemotherapy showed survival benefit, suggesting that targeting macrophages as the key driver of blood vessel dysmorphia in glioma progression presents opportunities to improve efficacy of chemotherapeutic agents. We propose that vessel dysfunction is not simply a general feature of tumor vessel formation, but rather an emergent property resulting from a dynamic and functional reorganization of the tumor stroma and its angiogenic influences. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

  17. HIFU procedures at moderate intensities-effect of large blood vessels

    International Nuclear Information System (INIS)

    Hariharan, P; Myers, M R; Banerjee, R K

    2007-01-01

    A three-dimensional computational model is presented for studying the efficacy of high-intensity focused ultrasound (HIFU) procedures targeted near large blood vessels. The analysis applies to procedures performed at intensities below the threshold for cavitation, boiling and highly nonlinear propagation, but high enough to increase tissue temperature a few degrees per second. The model is based upon the linearized KZK equation and the bioheat equation in tissue. In the blood vessel the momentum and energy equations are satisfied. The model is first validated in a tissue phantom, to verify the absence of bubble formation and nonlinear effects. Temperature rise and lesion-volume calculations are then shown for different beam locations and orientations relative to a large vessel. Both single and multiple ablations are considered. Results show that when the vessel is located within about a beam width (few mm) of the ultrasound beam, significant reduction in lesion volume is observed due to blood flow. However, for gaps larger than a beam width, blood flow has no major effect on the lesion formation. Under the clinically representative conditions considered, the lesion volume is reduced about 40% (relative to the no-flow case) when the beam is parallel to the blood vessel, compared to about 20% for a perpendicular orientation. Procedures involving multiple ablation sites are affected less by blood flow than single ablations. The model also suggests that optimally focused transducers can generate lesions that are significantly larger (>2 times) than the ones produced by highly focused beams

  18. HIFU procedures at moderate intensities-effect of large blood vessels

    Energy Technology Data Exchange (ETDEWEB)

    Hariharan, P [Mechanical, Industrial, and Nuclear Engineering Department, University of Cincinnati, Cincinnati, OH (United States); Myers, M R [Division of Solid and Fluid Mechanics, Center for Devices and Radiological Health, US Food and Drug Administration, 10903 New Hampshire Avenue, Building 62, Silver Spring, MD 20993-0002 (United States); Banerjee, R K [Mechanical, Industrial, and Nuclear Engineering Department, University of Cincinnati, Cincinnati, OH (United States)

    2007-07-21

    A three-dimensional computational model is presented for studying the efficacy of high-intensity focused ultrasound (HIFU) procedures targeted near large blood vessels. The analysis applies to procedures performed at intensities below the threshold for cavitation, boiling and highly nonlinear propagation, but high enough to increase tissue temperature a few degrees per second. The model is based upon the linearized KZK equation and the bioheat equation in tissue. In the blood vessel the momentum and energy equations are satisfied. The model is first validated in a tissue phantom, to verify the absence of bubble formation and nonlinear effects. Temperature rise and lesion-volume calculations are then shown for different beam locations and orientations relative to a large vessel. Both single and multiple ablations are considered. Results show that when the vessel is located within about a beam width (few mm) of the ultrasound beam, significant reduction in lesion volume is observed due to blood flow. However, for gaps larger than a beam width, blood flow has no major effect on the lesion formation. Under the clinically representative conditions considered, the lesion volume is reduced about 40% (relative to the no-flow case) when the beam is parallel to the blood vessel, compared to about 20% for a perpendicular orientation. Procedures involving multiple ablation sites are affected less by blood flow than single ablations. The model also suggests that optimally focused transducers can generate lesions that are significantly larger (>2 times) than the ones produced by highly focused beams.

  19. THE ALGORITHM OF DETERMINATION OF EYE FUNDUS VESSELS BLOOD FLOW CHARACTERISTICS ON VIDEOSEQUENCE

    Directory of Open Access Journals (Sweden)

    O. V. Nedzvedz

    2018-01-01

    Full Text Available The method of determination of the dynamic characteristics like the vessel diameter change, the linear and volume blood velocities in the vessels of the eye fundus is considered. Such characteristics allow to determine blood flow changes in the microvasculature affecting the blood flow in the brain, kidneys and coronary vessels. Developed algorithm includes four stages: the video sequence stabilization, the vessels segmentation with the help of a neural network, the determination of the instantaneous velocity in the vessels based on the optical flow and the analysis of the results.

  20. New algorithm for detecting smaller retinal blood vessels in fundus images

    Science.gov (United States)

    LeAnder, Robert; Bidari, Praveen I.; Mohammed, Tauseef A.; Das, Moumita; Umbaugh, Scott E.

    2010-03-01

    About 4.1 million Americans suffer from diabetic retinopathy. To help automatically diagnose various stages of the disease, a new blood-vessel-segmentation algorithm based on spatial high-pass filtering was developed to automatically segment blood vessels, including the smaller ones, with low noise. Methods: Image database: Forty, 584 x 565-pixel images were collected from the DRIVE image database. Preprocessing: Green-band extraction was used to obtain better contrast, which facilitated better visualization of retinal blood vessels. A spatial highpass filter of mask-size 11 was applied. A histogram stretch was performed to enhance contrast. A median filter was applied to mitigate noise. At this point, the gray-scale image was converted to a binary image using a binary thresholding operation. Then, a NOT operation was performed by gray-level value inversion between 0 and 255. Postprocessing: The resulting image was AND-ed with its corresponding ring mask to remove the outer-ring (lens-edge) artifact. At this point, the above algorithm steps had extracted most of the major and minor vessels, with some intersections and bifurcations missing. Vessel segments were reintegrated using the Hough transform. Results: After applying the Hough transform, both the average peak SNR and the RMS error improved by 10%. Pratt's Figure of Merit (PFM) was decreased by 6%. Those averages were better than [1] by 10-30%. Conclusions: The new algorithm successfully preserved the details of smaller blood vessels and should prove successful as a segmentation step for automatically identifying diseases that affect retinal blood vessels.

  1. Hypoxia-induced pulmonary vascular remodeling: cellular and molecular mechanisms.

    Science.gov (United States)

    Stenmark, Kurt R; Fagan, Karen A; Frid, Maria G

    2006-09-29

    Chronic hypoxic exposure induces changes in the structure of pulmonary arteries, as well as in the biochemical and functional phenotypes of each of the vascular cell types, from the hilum of the lung to the most peripheral vessels in the alveolar wall. The magnitude and the specific profile of the changes depend on the species, sex, and the developmental stage at which the exposure to hypoxia occurred. Further, hypoxia-induced changes are site specific, such that the remodeling process in the large vessels differs from that in the smallest vessels. The cellular and molecular mechanisms vary and depend on the cellular composition of vessels at particular sites along the longitudinal axis of the pulmonary vasculature, as well as on local environmental factors. Each of the resident vascular cell types (ie, endothelial, smooth muscle, adventitial fibroblast) undergo site- and time-dependent alterations in proliferation, matrix protein production, expression of growth factors, cytokines, and receptors, and each resident cell type plays a specific role in the overall remodeling response. In addition, hypoxic exposure induces an inflammatory response within the vessel wall, and the recruited circulating progenitor cells contribute significantly to the structural remodeling and persistent vasoconstriction of the pulmonary circulation. The possibility exists that the lung or lung vessels also contain resident progenitor cells that participate in the remodeling process. Thus the hypoxia-induced remodeling of the pulmonary circulation is a highly complex process where numerous interactive events must be taken into account as we search for newer, more effective therapeutic interventions. This review provides perspectives on each of the aforementioned areas.

  2. Improvement of retinal blood vessel detection using morphological component analysis.

    Science.gov (United States)

    Imani, Elaheh; Javidi, Malihe; Pourreza, Hamid-Reza

    2015-03-01

    Detection and quantitative measurement of variations in the retinal blood vessels can help diagnose several diseases including diabetic retinopathy. Intrinsic characteristics of abnormal retinal images make blood vessel detection difficult. The major problem with traditional vessel segmentation algorithms is producing false positive vessels in the presence of diabetic retinopathy lesions. To overcome this problem, a novel scheme for extracting retinal blood vessels based on morphological component analysis (MCA) algorithm is presented in this paper. MCA was developed based on sparse representation of signals. This algorithm assumes that each signal is a linear combination of several morphologically distinct components. In the proposed method, the MCA algorithm with appropriate transforms is adopted to separate vessels and lesions from each other. Afterwards, the Morlet Wavelet Transform is applied to enhance the retinal vessels. The final vessel map is obtained by adaptive thresholding. The performance of the proposed method is measured on the publicly available DRIVE and STARE datasets and compared with several state-of-the-art methods. An accuracy of 0.9523 and 0.9590 has been respectively achieved on the DRIVE and STARE datasets, which are not only greater than most methods, but are also superior to the second human observer's performance. The results show that the proposed method can achieve improved detection in abnormal retinal images and decrease false positive vessels in pathological regions compared to other methods. Also, the robustness of the method in the presence of noise is shown via experimental result. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Aminopeptidase A is a functional target in angiogenic blood vessels.

    Science.gov (United States)

    Marchiò, Serena; Lahdenranta, Johanna; Schlingemann, Reinier O; Valdembri, Donatella; Wesseling, Pieter; Arap, Marco A; Hajitou, Amin; Ozawa, Michael G; Trepel, Martin; Giordano, Ricardo J; Nanus, David M; Dijkman, Henri B P M; Oosterwijk, Egbert; Sidman, Richard L; Cooper, Max D; Bussolino, Federico; Pasqualini, Renata; Arap, Wadih

    2004-02-01

    We show that a membrane-associated protease, aminopeptidase A (APA), is upregulated and enzymatically active in blood vessels of human tumors. To gain mechanistic insight, we evaluated angiogenesis in APA null mice. We found that, although these mice develop normally, they fail to mount the expected angiogenic response to hypoxia or growth factors. We then isolated peptide inhibitors of APA from a peptide library and show that they specifically bind to and inhibit APA, suppress migration and proliferation of endothelial cells, inhibit angiogenesis, and home to tumor blood vessels. Finally, we successfully treated tumor-bearing mice with APA binding peptides or anti-APA blocking monoclonal antibodies. These data show that APA is a regulator of blood vessel formation, and can serve as a functional vascular target.

  4. Endothelium derived nitric oxide synthase negatively regulates the PDGF-survivin pathway during flow-dependent vascular remodeling.

    Directory of Open Access Journals (Sweden)

    Jun Yu

    Full Text Available Chronic alterations in blood flow initiate structural changes in vessel lumen caliber to normalize shear stress. The loss of endothelial derived nitric oxide synthase (eNOS in mice promotes abnormal flow dependent vascular remodeling, thus uncoupling mechanotransduction from adaptive vascular remodeling. However, the mechanisms of how the loss of eNOS promotes abnormal remodeling are not known. Here we show that abnormal flow-dependent remodeling in eNOS knockout mice (eNOS (-/- is associated with activation of the platelet derived growth factor (PDGF signaling pathway leading to the induction of the inhibitor of apoptosis, survivin. Interfering with PDGF signaling or survivin function corrects the abnormal remodeling seen in eNOS (-/- mice. Moreover, nitric oxide (NO negatively regulates PDGF driven survivin expression and cellular proliferation in cultured vascular smooth muscle cells. Collectively, our data suggests that eNOS negatively regulates the PDGF-survivin axis to maintain proportional flow-dependent luminal remodeling and vascular quiescence.

  5. Automatic detection of blood vessels in retinal images for diabetic retinopathy diagnosis.

    Science.gov (United States)

    Raja, D Siva Sundhara; Vasuki, S

    2015-01-01

    Diabetic retinopathy (DR) is a leading cause of vision loss in diabetic patients. DR is mainly caused due to the damage of retinal blood vessels in the diabetic patients. It is essential to detect and segment the retinal blood vessels for DR detection and diagnosis, which prevents earlier vision loss in diabetic patients. The computer aided automatic detection and segmentation of blood vessels through the elimination of optic disc (OD) region in retina are proposed in this paper. The OD region is segmented using anisotropic diffusion filter and subsequentially the retinal blood vessels are detected using mathematical binary morphological operations. The proposed methodology is tested on two different publicly available datasets and achieved 93.99% sensitivity, 98.37% specificity, 98.08% accuracy in DRIVE dataset and 93.6% sensitivity, 98.96% specificity, and 95.94% accuracy in STARE dataset, respectively.

  6. Subconjunctival Hemorrhage (Broken Blood Vessel in Eye)

    Science.gov (United States)

    Subconjunctival hemorrhage (broken blood vessel in eye) Overview A subconjunctival hemorrhage (sub-kun-JUNK-tih-vul HEM-uh-ruj) ... may not even realize you have a subconjunctival hemorrhage until you look in the mirror and notice ...

  7. Polymer-based blood vessel models with micro-temperature sensors in EVE

    Science.gov (United States)

    Mizoshiri, Mizue; Ito, Yasuaki; Hayakawa, Takeshi; Maruyama, Hisataka; Sakurai, Junpei; Ikeda, Seiichi; Arai, Fumihito; Hata, Seiichi

    2017-04-01

    Cu-based micro-temperature sensors were directly fabricated on poly(dimethylsiloxane) (PDMS) blood vessel models in EVE using a combined process of spray coating and femtosecond laser reduction of CuO nanoparticles. CuO nanoparticle solution coated on a PDMS blood vessel model are thermally reduced and sintered by focused femtosecond laser pulses in atmosphere to write the sensors. After removing the non-irradiated CuO nanoparticles, Cu-based microtemperature sensors are formed. The sensors are thermistor-type ones whose temperature dependences of the resistance are used for measuring temperature inside the blood vessel model. This fabrication technique is useful for direct-writing of Cu-based microsensors and actuators on arbitrary nonplanar substrates.

  8. Remodeling of Tumor Stroma and Response to Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Johansson, Anna; Ganss, Ruth, E-mail: ganss@waimr.uwa.edu.au [Western Australian Institute for Medical Research, Centre for Medical Research, University of Western Australia, Perth 6000 (Australia)

    2012-03-27

    Solid tumors are intrinsically resistant to therapy. Cancer progression occurs when tumor cells orchestrate responses from diverse stromal cell types such as blood vessels and their support cells, inflammatory cells, and fibroblasts; these cells collectively form the tumor microenvironment and provide direct support for tumor growth, but also evasion from cytotoxic, immune and radiation therapies. An indirect result of abnormal and leaky blood vessels in solid tumors is high interstitial fluid pressure, which reduces drug penetration, but also creates a hypoxic environment that further augments tumor cell growth and metastatic spread. Importantly however, studies during the last decade have shown that the tumor stroma, including the vasculature, can be modulated, or re-educated, to allow better delivery of chemotherapeutic drugs or enhance the efficiency of active immune therapy. Such remodeling of the tumor stroma using genetic, pharmacological and other therapeutic approaches not only enhances selective access into tumors but also reduces toxic side effects. This review focuses on recent novel concepts to modulate tumor stroma and thus locally increase therapeutic efficacy.

  9. Remodeling of Tumor Stroma and Response to Therapy

    International Nuclear Information System (INIS)

    Johansson, Anna; Ganss, Ruth

    2012-01-01

    Solid tumors are intrinsically resistant to therapy. Cancer progression occurs when tumor cells orchestrate responses from diverse stromal cell types such as blood vessels and their support cells, inflammatory cells, and fibroblasts; these cells collectively form the tumor microenvironment and provide direct support for tumor growth, but also evasion from cytotoxic, immune and radiation therapies. An indirect result of abnormal and leaky blood vessels in solid tumors is high interstitial fluid pressure, which reduces drug penetration, but also creates a hypoxic environment that further augments tumor cell growth and metastatic spread. Importantly however, studies during the last decade have shown that the tumor stroma, including the vasculature, can be modulated, or re-educated, to allow better delivery of chemotherapeutic drugs or enhance the efficiency of active immune therapy. Such remodeling of the tumor stroma using genetic, pharmacological and other therapeutic approaches not only enhances selective access into tumors but also reduces toxic side effects. This review focuses on recent novel concepts to modulate tumor stroma and thus locally increase therapeutic efficacy

  10. Blood Vessel Normalization in the Hamster Oral Cancer Model for Experimental Cancer Therapy Studies

    Energy Technology Data Exchange (ETDEWEB)

    Ana J. Molinari; Romina F. Aromando; Maria E. Itoiz; Marcela A. Garabalino; Andrea Monti Hughes; Elisa M. Heber; Emiliano C. C. Pozzi; David W. Nigg; Veronica A. Trivillin; Amanda E. Schwint

    2012-07-01

    Normalization of tumor blood vessels improves drug and oxygen delivery to cancer cells. The aim of this study was to develop a technique to normalize blood vessels in the hamster cheek pouch model of oral cancer. Materials and Methods: Tumor-bearing hamsters were treated with thalidomide and were compared with controls. Results: Twenty eight hours after treatment with thalidomide, the blood vessels of premalignant tissue observable in vivo became narrower and less tortuous than those of controls; Evans Blue Dye extravasation in tumor was significantly reduced (indicating a reduction in aberrant tumor vascular hyperpermeability that compromises blood flow), and tumor blood vessel morphology in histological sections, labeled for Factor VIII, revealed a significant reduction in compressive forces. These findings indicated blood vessel normalization with a window of 48 h. Conclusion: The technique developed herein has rendered the hamster oral cancer model amenable to research, with the potential benefit of vascular normalization in head and neck cancer therapy.

  11. Regulation of blood vessels by prolactin and vasoinhibins.

    Science.gov (United States)

    Clapp, Carmen; Thebault, Stéphanie; Macotela, Yazmín; Moreno-Carranza, Bibiana; Triebel, Jakob; Martínez de la Escalera, Gonzalo

    2015-01-01

    Prolactin (PRL) stimulates the growth of new blood vessels (angiogenesis) either directly through actions on endothelial cells or indirectly by upregulating proangiogenic factors like vascular endothelial growth factor (VEGF). Moreover, PRL acquires antiangiogenic properties after undergoing proteolytic cleavage to vasoinhibins, a family of PRL fragments (including 16 kDa PRL) with potent antiangiogenic, vasoconstrictive, and antivasopermeability effects. In view of the opposing actions of PRL and vasoinhibins, the regulation of the proteases responsible for specific PRL cleavage represents an efficient mechanism for controlling blood vessel growth and function. This review briefly describes the vascular actions of PRL and vasoinhibins, and addresses how their interplay could help drive biological effects of PRL in the context of health and disease.

  12. Melanopsin mediates light-dependent relaxation in blood vessels.

    Science.gov (United States)

    Sikka, Gautam; Hussmann, G Patrick; Pandey, Deepesh; Cao, Suyi; Hori, Daijiro; Park, Jong Taek; Steppan, Jochen; Kim, Jae Hyung; Barodka, Viachaslau; Myers, Allen C; Santhanam, Lakshmi; Nyhan, Daniel; Halushka, Marc K; Koehler, Raymond C; Snyder, Solomon H; Shimoda, Larissa A; Berkowitz, Dan E

    2014-12-16

    Melanopsin (opsin4; Opn4), a non-image-forming opsin, has been linked to a number of behavioral responses to light, including circadian photo-entrainment, light suppression of activity in nocturnal animals, and alertness in diurnal animals. We report a physiological role for Opn4 in regulating blood vessel function, particularly in the context of photorelaxation. Using PCR, we demonstrate that Opn4 (a classic G protein-coupled receptor) is expressed in blood vessels. Force-tension myography demonstrates that vessels from Opn4(-/-) mice fail to display photorelaxation, which is also inhibited by an Opn4-specific small-molecule inhibitor. The vasorelaxation is wavelength-specific, with a maximal response at ∼430-460 nm. Photorelaxation does not involve endothelial-, nitric oxide-, carbon monoxide-, or cytochrome p450-derived vasoactive prostanoid signaling but is associated with vascular hyperpolarization, as shown by intracellular membrane potential measurements. Signaling is both soluble guanylyl cyclase- and phosphodiesterase 6-dependent but protein kinase G-independent. β-Adrenergic receptor kinase 1 (βARK 1 or GRK2) mediates desensitization of photorelaxation, which is greatly reduced by GRK2 inhibitors. Blue light (455 nM) regulates tail artery vasoreactivity ex vivo and tail blood blood flow in vivo, supporting a potential physiological role for this signaling system. This endogenous opsin-mediated, light-activated molecular switch for vasorelaxation might be harnessed for therapy in diseases in which altered vasoreactivity is a significant pathophysiologic contributor.

  13. An approach to localize the retinal blood vessels using bit planes and centerline detection.

    Science.gov (United States)

    Fraz, M M; Barman, S A; Remagnino, P; Hoppe, A; Basit, A; Uyyanonvara, B; Rudnicka, A R; Owen, C G

    2012-11-01

    The change in morphology, diameter, branching pattern or tortuosity of retinal blood vessels is an important indicator of various clinical disorders of the eye and the body. This paper reports an automated method for segmentation of blood vessels in retinal images. A unique combination of techniques for vessel centerlines detection and morphological bit plane slicing is presented to extract the blood vessel tree from the retinal images. The centerlines are extracted by using the first order derivative of a Gaussian filter in four orientations and then evaluation of derivative signs and average derivative values is performed. Mathematical morphology has emerged as a proficient technique for quantifying the blood vessels in the retina. The shape and orientation map of blood vessels is obtained by applying a multidirectional morphological top-hat operator with a linear structuring element followed by bit plane slicing of the vessel enhanced grayscale image. The centerlines are combined with these maps to obtain the segmented vessel tree. The methodology is tested on three publicly available databases DRIVE, STARE and MESSIDOR. The results demonstrate that the performance of the proposed algorithm is comparable with state of the art techniques in terms of accuracy, sensitivity and specificity. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  14. Correlation between blood and lymphatic vessel density and results of contrast-enhanced spectral mammography.

    Science.gov (United States)

    Luczynska, Elzbieta; Niemiec, Joanna; Ambicka, Aleksandra; Adamczyk, Agnieszka; Walasek, Tomasz; Ryś, Janusz; Sas-Korczyńska, Beata

    2015-09-01

    Contrast-enhanced spectral mammography (CESM) is a novel technique used for detection of tumour vascularity by imaging the moment in which contrast, delivered to the lesion by blood vessels, leaks out of them, and flows out through lymphatic vessels. In our study, we included 174 women for whom spectral mammography was performed for diagnostic purposes. The relationship between enhancement in CESM and blood vessel density (BVD), lymphatic vessel density (LVD) or the percentage of fields with at least one lymphatic vessel (distribution of podoplanin-positive vessels - DPV) and other related parameters was assessed in 55 cases. BVD, LVD and DPV were assessed immunohistochemically, applying podoplanin and CD31/CD34 as markers of lymphatic and blood vessels, respectively. The sensitivity (in detection of malignant lesions) of CESM was 100%, while its specificity - 39%. We found a significant positive correlation between the intensity of enhancement in CESM and BVD (p = 0.007, r = 0.357) and a negative correlation between the intensity of enhancement in CESM and DPV (p = 0.003, r = -0.390). Lesions with the highest enhancement in CESM showed a high number of blood vessels and a low number of lymphatics. 1) CESM is a method characterized by high sensitivity and acceptable specificity; 2) the correlation between CESM results and blood/lymphatic vessel density confirms its utility in detection of tissue angiogenesis and/or lymphangiogenesis.

  15. Feasibility of Using the Marginal Blood Vessels as Reference Landmarks for CT Colonography

    Science.gov (United States)

    Wei, Zhuoshi; Yao, Jianhua; Wang, Shijun; Liu, Jiamin; Dwyer, Andrew J.; Pickhardt, Perry J.; Nowinski, Wieslaw L.; Summers, Ronald M.

    2015-01-01

    OBJECTIVE The purpose of this study was to show the spatial relationship of the colonic marginal blood vessels and the teniae coli on CT colonography (CTC) and the use of the marginal blood vessels for supine-prone registration of polyps and for determination of proper connectivity of collapsed colonic segments. MATERIALS AND METHODS We manually labeled the marginal blood vessels on 15 CTC examinations. Colon segmentation, centerline extraction, teniae detection, and teniae identification were automatically performed. For assessment of their spatial relationships, the distances from the marginal blood vessels to the three teniae coli and to the colon were measured. Student t tests (paired, two-tailed) were performed to evaluate the differences among these distances. To evaluate the reliability of the marginal vessels as reference points for polyp correlation, we analyzed 20 polyps from 20 additional patients who underwent supine and prone CTC. The average difference of the circumferential polyp position on the supine and prone scans was computed. Student t tests (paired, two-tailed) were performed to evaluate the supine-prone differences of the distance. We performed a study on 10 CTC studies from 10 patients with collapsed colonic segments by manually tracing the marginal blood vessels near the collapsed regions to resolve the ambiguity of the colon path. RESULTS The average distances (± SD) from the marginal blood vessels to the tenia mesocolica, tenia omentalis, and tenia libera were 20.1 ± 3.1 mm (95% CI, 18.5–21.6 mm), 39.5 ± 4.8 mm (37.1–42.0 mm), and 36.9 ± 4.2 mm (34.8–39.1 mm), respectively. Pairwise comparison showed that these distances to the tenia libera and tenia omentalis were significantly different from the distance to the tenia mesocolica (p marginal blood vessels to the colon wall was 15.3 ± 2.0 mm (14.2–16.3 mm). For polyp localization, the average difference of the circumferential polyp position on the supine and prone scans was 9

  16. Customizable engineered blood vessels using 3D printed inserts.

    Science.gov (United States)

    Pinnock, Cameron B; Meier, Elizabeth M; Joshi, Neeraj N; Wu, Bin; Lam, Mai T

    2016-04-15

    Current techniques for tissue engineering blood vessels are not customizable for vascular size variation and vessel wall thickness. These critical parameters vary widely between the different arteries in the human body, and the ability to engineer vessels of varying sizes could increase capabilities for disease modeling and treatment options. We present an innovative method for producing customizable, tissue engineered, self-organizing vascular constructs by replicating a major structural component of blood vessels - the smooth muscle layer, or tunica media. We utilize a unique system combining 3D printed plate inserts to control construct size and shape, and cell sheets supported by a temporary fibrin hydrogel to encourage cellular self-organization into a tubular form resembling a natural artery. To form the vascular construct, 3D printed inserts are adhered to tissue culture plates, fibrin hydrogel is deposited around the inserts, and human aortic smooth muscle cells are then seeded atop the fibrin hydrogel. The gel, aided by the innate contractile properties of the smooth muscle cells, aggregates towards the center post insert, creating a tissue ring of smooth muscle cells. These rings are then stacked into the final tubular construct. Our methodology is robust, easily repeatable and allows for customization of cellular composition, vessel wall thickness, and length of the vessel construct merely by varying the size of the 3D printed inserts. This platform has potential for facilitating more accurate modeling of vascular pathology, serving as a drug discovery tool, or for vessel repair in disease treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Effect of non-Newtonian characteristics of blood on magnetic particle capture in occluded blood vessel

    Science.gov (United States)

    Bose, Sayan; Banerjee, Moloy

    2015-01-01

    Magnetic nanoparticles drug carriers continue to attract considerable interest for drug targeting in the treatment of cancer and other pathological conditions. Magnetic carrier particles with surface-bound drug molecules are injected into the vascular system upstream from the desired target site, and are captured at the target site via a local applied magnetic field. Herein, a numerical investigation of steady magnetic drug targeting (MDT) using functionalized magnetic micro-spheres in partly occluded blood vessel having a 90° bent is presented considering the effects of non-Newtonian characteristics of blood. An Eulerian-Lagrangian technique is adopted to resolve the hemodynamic flow and the motion of the magnetic particles in the flow using ANSYS FLUENT. An implantable infinitely long cylindrical current carrying conductor is used to create the requisite magnetic field. Targeted transport of the magnetic particles in a partly occluded vessel differs distinctly from the same in a regular unblocked vessel. Parametric investigation is conducted and the influence of the insert configuration and its position from the central plane of the artery (zoffset), particle size (dp) and its magnetic property (χ) and the magnitude of current (I) on the "capture efficiency" (CE) is reported. Analysis shows that there exists an optimum regime of operating parameters for which deposition of the drug carrying magnetic particles in a target zone on the partly occluded vessel wall can be maximized. The results provide useful design bases for in vitro set up for the investigation of MDT in stenosed blood vessels.

  18. Mass Spectrometry and Antibody-Based Characterization of Blood Vessels from Brachylophosaurus canadensis.

    Science.gov (United States)

    Cleland, Timothy P; Schroeter, Elena R; Zamdborg, Leonid; Zheng, Wenxia; Lee, Ji Eun; Tran, John C; Bern, Marshall; Duncan, Michael B; Lebleu, Valerie S; Ahlf, Dorothy R; Thomas, Paul M; Kalluri, Raghu; Kelleher, Neil L; Schweitzer, Mary H

    2015-12-04

    Structures similar to blood vessels in location, morphology, flexibility, and transparency have been recovered after demineralization of multiple dinosaur cortical bone fragments from multiple specimens, some of which are as old as 80 Ma. These structures were hypothesized to be either endogenous to the bone (i.e., of vascular origin) or the result of biofilm colonizing the empty osteonal network after degradation of original organic components. Here, we test the hypothesis that these structures are endogenous and thus retain proteins in common with extant archosaur blood vessels that can be detected with high-resolution mass spectrometry and confirmed by immunofluorescence. Two lines of evidence support this hypothesis. First, peptide sequencing of Brachylophosaurus canadensis blood vessel extracts is consistent with peptides comprising extant archosaurian blood vessels and is not consistent with a bacterial, cellular slime mold, or fungal origin. Second, proteins identified by mass spectrometry can be localized to the tissues using antibodies specific to these proteins, validating their identity. Data are available via ProteomeXchange with identifier PXD001738.

  19. Leukemic Cells "Gas Up" Leaky Bone Marrow Blood Vessels.

    Science.gov (United States)

    Itkin, Tomer; Rafii, Shahin

    2017-09-11

    In this issue of Cancer Cell, Passaro et al. demonstrate how leukemia through aberrant induction of reactive oxygen species and nitric oxide production trigger marrow vessel leakiness, instigating pro-leukemic function. Disrupted tumor blood vessels promote exhaustion of non-malignant stem and progenitor cells and may facilitate leukemia relapse following chemotherapeutic treatment. Copyright © 2017. Published by Elsevier Inc.

  20. Peptide-Mediated Liposomal Drug Delivery System Targeting Tumor Blood Vessels in Anticancer Therapy

    Directory of Open Access Journals (Sweden)

    Han-Chung Wu

    2010-01-01

    Full Text Available Solid tumors are known to recruit new blood vessels to support their growth. Therefore, unique molecules expressed on tumor endothelial cells can function as targets for the antiangiogenic therapy of cancer. Current efforts are focusing on developing therapeutic agents capable of specifically targeting cancer cells and tumor-associated microenvironments including tumor blood vessels. These therapies hold the promise of high efficacy and low toxicity. One recognized strategy for improving the therapeutic effectiveness of conventional chemotherapeutics is to encapsulate anticancer drugs into targeting liposomes that bind to the cell surface receptors expressed on tumor-associated endothelial cells. These anti-angiogenic drug delivery systems could be used to target both tumor blood vessels as well as the tumor cells, themselves. This article reviews the mechanisms and advantages of various present and potential methods using peptide-conjugated liposomes to specifically destroy tumor blood vessels in anticancer therapy.

  1. VASCULAR REMODELING AND HEART RATE VARIABILITY IN DIFFERENT ANTIHYPERTENSIVE THERAPIES

    Directory of Open Access Journals (Sweden)

    E. D. Golovanova

    2008-01-01

    Full Text Available Aim. To study the effect of the long-term antihypertensive monotherapy with indapamide (Arifon Retard, 1,5 mg/d, metoprolol tartrate (Egilok Retard, 50 mg/d and combined therapy with indapamide and perindopril (Noliprel Forte, 1 tab/d: perindopril 4 mg and indapamide 1,25 mg on pulse wave velocity (PWV, cardio-ankle vascular index (CAVI and the sympathetic system activity.Material and methods. 88 patients, aged 30-59 y.o. (32 normotensive patients, 56 with arterial hypertension [HT] of 1-2 grades were examined. Biological age (BA was determined by the linear regression and the vascular wall age (VWA was estimated with the use of volume sphygmography (“VaSera-1000”, “Fucuda Denshi”, Japan. 39 patients with HT were randomized into 3 parallel groups with studied therapies lasted for 6 months. PWV, CAVI of the vessels of elastic, muscular and mixed types, blood pressure, measured in upper and lower extremities and heart rate variability (HRV were determined before and at the end of the therapies.Results. BA and VWA were elevated in all of patients with HT as compared with normotensive patients. The reduction in PWV and CAVI of the vessels of elastic and mixed types, HRV increase were found in patients with Arifon Retard monotherapy. Monotherapy with metoprolol significantly improved HVR without any influence on the vascular remodeling. Noliprel Forte significantly decreased in blood pressure in the upper and lower extremities, PWV and CAVI of the vessels of all types, decreased in VWA and increased in parasympathetic drive.Conclusion. Long-term therapy with Arifon Retard and Noliprel Forte resulted in decrease in vascular remodeling and increase in HRV simultaneously with significant antihypertensive effect in patients with HT. Metoprolol low doses therapy resulted in normalization of autonomic drive independently on antihypertensive action.

  2. Parametrically defined cerebral blood vessels as non-invasive blood input functions for brain PET studies

    International Nuclear Information System (INIS)

    Asselin, Marie-Claude; Cunningham, Vincent J; Amano, Shigeko; Gunn, Roger N; Nahmias, Claude

    2004-01-01

    A non-invasive alternative to arterial blood sampling for the generation of a blood input function for brain positron emission tomography (PET) studies is presented. The method aims to extract the dimensions of the blood vessel directly from PET images and to simultaneously correct the radioactivity concentration for partial volume and spillover. This involves simulation of the tomographic imaging process to generate images of different blood vessel and background geometries and selecting the one that best fits, in a least-squares sense, the acquired PET image. A phantom experiment was conducted to validate the method which was then applied to eight subjects injected with 6-[ 18 F]fluoro-L-DOPA and one subject injected with [ 11 C]CO-labelled red blood cells. In the phantom study, the diameter of syringes filled with an 11 C solution and inserted into a water-filled cylinder were estimated with an accuracy of half a pixel (1 mm). The radioactivity concentration was recovered to 100 ± 4% in the 8.7 mm diameter syringe, the one that most closely approximated the superior sagittal sinus. In the human studies, the method systematically overestimated the calibre of the superior sagittal sinus by 2-3 mm compared to measurements made in magnetic resonance venograms on the same subjects. Sources of discrepancies related to the anatomy of the blood vessel were found not to be fundamental limitations to the applicability of the method to human subjects. This method has the potential to provide accurate quantification of blood radioactivity concentration from PET images without the need for blood samples, corrections for delay and dispersion, co-registered anatomical images, or manually defined regions of interest

  3. Vascular Remodeling in Experimental Hypertension

    Directory of Open Access Journals (Sweden)

    Norma R. Risler

    2005-01-01

    Full Text Available The basic hemodynamic abnormality in hypertension is an increased peripheral resistance that is due mainly to a decreased vascular lumen derived from structural changes in the small arteries wall, named (as a whole vascular remodeling. The vascular wall is an active, flexible, and integrated organ made up of cellular (endothelial cells, smooth muscle cells, adventitia cells, and fibroblasts and noncellular (extracellular matrix components, which in a dynamic way change shape or number, or reorganize in response to physiological and pathological stimuli, maintaining the integrity of the vessel wall in physiological conditions or participating in the vascular changes in cardiovascular diseases such as hypertension. Research focused on new signaling pathways and molecules that can participate in the mechanisms of vascular remodeling has provided evidence showing that vascular structure is not only affected by blood pressure, but also by mechanisms that are independent of the increased pressure. This review will provide an overview of the evidence, explaining some of the pathophysiologic mechanisms participating in the development of the vascular remodeling, in experimental models of hypertension, with special reference to the findings in spontaneously hypertensive rats as a model of essential hypertension, and in fructose-fed rats as a model of secondary hypertension, in the context of the metabolic syndrome. The understanding of the mechanisms producing the vascular alterations will allow the development of novel pharmacological tools for vascular protection in hypertensive disease.

  4. Towards cavitation-enhanced permeability in blood vessel on a chip

    Science.gov (United States)

    De Luca, R.; Silvani, G.; Scognamiglio, C.; Sinibaldi, G.; Peruzzi, G.; Chinappi, M.; Kiani, M. F.; Casciola, C. M.

    2017-08-01

    The development of targeted delivery systems releasing pharmaceutical agents directly at the desired site of action may improve their therapeutic efficiency while minimizing damage to healthy tissues, toxicity to the patient and drug waste. In this context, we have developed a bio-inspired microdevice mimicking the tumour microvasculature which represents a valuable tool for assessing the enhancement of blood vessel permeability due to cavitation. This novel system allows us to investigate the effects of ultrasound-driven microbubbles that temporarily open the endothelial intercellular junctions allowing drug to extravasate blood vessels into tumour tissues. The blood vessel on a chip consists of a tissue chamber and two independent vascular channels (width 200 µm, height 100 µm, length 2762 µm) cultured with endothelial cells placed side-by-side and separated by a series of 3 µm pores. Its geometry and dimensions mimic the three-dimensional morphology, size and flow characteristics of microvessels in vivo. The early stage of this project had a twofold objective: 1. To define the protocol for culturing of Human Umbilical Vein Endothelial Cells (HUVECs) within the vascular channel; 2. To develop a fluorescence based microscopy technique for measuring permeability. We have developed a reliable and reproducible protocol to culture endothelial cells within the artificial vessels in a realistic manner: HUVECs show the typical elongated shape in the direction of flow, exhibit tight junction formation and form a continuous layer with a central lumen that completely covers the channels wall. As expected, the permeability of cell-free device is higher than the one cultured with HUVECs in the vascular channels. The proposed blood vessel on a chip and the permeability measurement protocol have a significant potential to allow for the study of cavitation-enhanced permeability of the endothelium and improve efficiency in screening drug delivery systems.

  5. A thresholding based technique to extract retinal blood vessels from fundus images

    Directory of Open Access Journals (Sweden)

    Jyotiprava Dash

    2017-12-01

    Full Text Available Retinal imaging has become the significant tool among all the medical imaging technology, due to its capability to extract many data which is linked to various eye diseases. So, the accurate extraction of blood vessel is necessary that helps the eye care specialists and ophthalmologist to identify the diseases at the early stages. In this paper, we have proposed a computerized technique for extraction of blood vessels from fundus images. The process is conducted in three phases: (i pre-processing where the image is enhanced using contrast limited adaptive histogram equalization and median filter, (ii segmentation using mean-C thresholding to extract retinal blood vessels, (iii post-processing where morphological cleaning operation is used to remove isolated pixels. The performance of the proposed method is tested on and experimental results show that our method achieve an accuracies of 0.955 and 0.954 on Digital retinal images for vessel extraction (DRIVE and Child heart and health study in England (CHASE_DB1 databases respectively.

  6. C1-esterase inhibitor protects against early vein graft remodeling under arterial blood pressure.

    Science.gov (United States)

    Krijnen, Paul A J; Kupreishvili, Koba; de Vries, Margreet R; Schepers, Abbey; Stooker, Wim; Vonk, Alexander B A; Eijsman, Leon; Van Hinsbergh, Victor W M; Zeerleder, Sacha; Wouters, Diana; van Ham, Marieke; Quax, Paul H A; Niessen, Hans W M

    2012-01-01

    Arterial pressure induced vein graft injury can result in endothelial loss, accelerated atherosclerosis and vein graft failure. Inflammation, including complement activation, is assumed to play a pivotal role herein. Here, we analyzed the effects of C1-esterase inhibitor (C1inh) on early vein graft remodeling. Human saphenous vein graft segments (n=8) were perfused in vitro with autologous blood either supplemented or not with purified human C1inh at arterial pressure for 6h. The vein segments and perfusion blood were analyzed for cell damage and complement activation. In addition, the effect of purified C1inh on vein graft remodeling was analyzed in vivo in atherosclerotic C57Bl6/ApoE3 Leiden mice, wherein donor caval veins were interpositioned in the common carotid artery. Application of C1inh in the in vitro perfusion model resulted in significantly higher blood levels and significantly more depositions of C1inh in the vein wall. This coincided with a significant reduction in endothelial loss and deposition of C3d and C4d in the vein wall, especially in the circular layer, compared to vein segments perfused without supplemented C1inh. Administration of purified C1inh significantly inhibited vein graft intimal thickening in vivo in atherosclerotic C57Bl6/ApoE3 Leiden mice, wherein donor caval veins were interpositioned in the common carotid artery. C1inh significantly protects against early vein graft remodeling, including loss of endothelium and intimal thickening. These data suggest that it may be worth considering its use in patients undergoing coronary artery bypass grafting. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  7. Wide-field absolute transverse blood flow velocity mapping in vessel centerline

    Science.gov (United States)

    Wu, Nanshou; Wang, Lei; Zhu, Bifeng; Guan, Caizhong; Wang, Mingyi; Han, Dingan; Tan, Haishu; Zeng, Yaguang

    2018-02-01

    We propose a wide-field absolute transverse blood flow velocity measurement method in vessel centerline based on absorption intensity fluctuation modulation effect. The difference between the light absorption capacities of red blood cells and background tissue under low-coherence illumination is utilized to realize the instantaneous and average wide-field optical angiography images. The absolute fuzzy connection algorithm is used for vessel centerline extraction from the average wide-field optical angiography. The absolute transverse velocity in the vessel centerline is then measured by a cross-correlation analysis according to instantaneous modulation depth signal. The proposed method promises to contribute to the treatment of diseases, such as those related to anemia or thrombosis.

  8. Polysaccharides from astragali radix restore chemical-induced blood vessel loss in zebrafish

    Science.gov (United States)

    2012-01-01

    Background Astragali Radix has been used widely for the treatment of cardiovascular and cerebrovascular diseases, and to enhance endurance and stamina in traditional Chinese medicine (TCM) for over 2000 years. The polysaccharide constituents of Astragali Radix (ARP) are considered as one of the major constituents contributing to the multiple pharmacological effects of this medicinal plant. The purpose of the study is to evaluate the vascular regenerative activities of ARPs in a chemically-induced blood vessel loss model in zebrafish. Methods Blood vessel loss was induced in both Tg(fli-1a:EGFP)y1 and Tg(fli-1a:nEGFP)y7 embryos by administration of 300 nM VEGFR tyrosine kinase inhibitor II (VRI) for 3 h at 24 hpf (hour post-fertilization). Then, the blood vessel damaged zebrafish were treated with ARPs for 21 h and 45 h after VRI withdrawal. Morphological changes in intersegmental vessels (ISVs) of zebrafish larvae were observed under the fluorescence microscope and measured quantitatively. The rescue effect of ARPs in the zebrafish models was validated by measuring the relative mRNA expressions of Kdrl, Kdr and Flt-1 using real-time PCR. Results Two polysaccharide fractions, P4 (50000 D 0.1 μm), isolated from Astragali Radix by ultrafiltration, produced a significant and dose-dependent recovery in VRI-induced blood vessel loss in zebrafish. Furthermore, the down-regulation of Flk-1 and Flt-1 mRNA expression induced by VRI was reversed by treatment with P4. Conclusion The present study demonstrates that P4 isolated from Astragali Radix reduces VRI-induced blood vessel loss in zebrafish. These findings support the hypothesis that polysaccharides are one of the active constituents in Astragali Radix, contributing to its beneficial effect on treatment of diseases associated with a deficiency in angiogenesis. PMID:22357377

  9. Fetal blood vessel count increases in compensation of hypoxia in premature placentas

    Directory of Open Access Journals (Sweden)

    K. Kartini

    2015-04-01

    Full Text Available Background Prematurity refers to live births before 37 weeks of gestation, wherein the baby is born before the body and its organ systems achieve perfect maturity, and this disorder is still a global problem. The high incidence of prematurity is a problem in developing and also in developed countries. Certain conditions accompanying pregnancies like preeclampsia, infection, and placental insufficiency, may trigger uterine hypoxia, causing premature birth. The placental condition is related to the intra-uterine fetal condition. In prolonged placental hypoxia, there occurs a compensatory mechanism, i.e. an increase in placental angiogenesis. This study aimed to evaluate the effect of hypoxia on fetal blood vessel count as compensatory mechanism for tissue hypoxia. Methods An observational-analytical cross-sectional design using paraffin blocks of conserved premature placentas, comprising 31 samples of hypoxic premature placentas and 28 samples of non-hypoxic premature placentas, selected using non-random consecutive sampling. The samples were made into slides and stained with hematoxylin-eosin for assessment of histological structure, including fetal blood vessel count and integrity, villus conditions, syncytiotrophoblastic nuclear changes, and syncytiotrophoblastic nuclear aggregation. Mann-Whitney test was used to compare the difference of blood vessel count between groups. Results Assessment of histological structure showed a significant increase in fetal blood vessel count in the hypoxic group [8.00 (5-15] as compared with the non-hypoxic group [7.50 (3-15]. Conclusion The hypoxia in premature placentas caused an increase in the number of fetal blood vessels as a form of compensation for disturbed oxygen homeostasis.

  10. Fetal blood vessel count increases in compensation of hypoxia in premature placentas

    Directory of Open Access Journals (Sweden)

    K Kartini

    2016-02-01

    Full Text Available BACKGROUND Prematurity refers to live births before 37 weeks of gestation, wherein the baby is born before the body and its organ systems achieve perfect maturity, and this disorder is still a global problem. The high incidence of prematurity is a problem in developing and also in developed countries. Certain conditions accompanying pregnancies like preeclampsia, infection, and placental insufficiency, may trigger uterine hypoxia, causing premature birth. The placental condition is related to the intra-uterine fetal condition. In prolonged placental hypoxia, there occurs a compensatory mechanism, i.e. an increase in placental angiogenesis. This study aimed to evaluate the effect of hypoxia on fetal blood vessel count as compensatory mechanism for tissue hypoxia. METHODS An observational-analytical cross-sectional design using paraffin blocks of conserved premature placentas, comprising 31 samples of hypoxic premature placentas and 28 samples of non-hypoxic premature placentas, selected using non-random consecutive sampling. The samples were made into slides and stained with hematoxylin-eosin for assessment of histological structure, including fetal blood vessel count and integrity, villus conditions, syncytiotrophoblastic nuclear changes, and syncytiotrophoblastic nuclear aggregation. Mann-Whitney test was used to compare the difference of blood vessel count between groups. RESULTS Assessment of histological structure showed a significant increase in fetal blood vessel count in the hypoxic group [8.00 (5-15] as compared with the non-hypoxic group [7.50 (3-15]. CONCLUSION The hypoxia in premature placentas caused an increase in the number of fetal blood vessels as a form of compensation for disturbed oxygen homeostasis.

  11. Accuracy of geometrical modelling of heat transfer from tissue to blood vessels

    NARCIS (Netherlands)

    Leeuwen, van G.M.J.; Kotte, A.N.T.J.; Bree, de J.; Koijk, van der J.F.; Crezee, J.; Lagendijk, J.J.W.

    1997-01-01

    We have developed a thermal model in which blood vessels are described as geometrical objects, 3D curves with associated diameters. Here the behaviour of the model is examined for low resolutions compared with the vessel diameter and for strongly curved vessels. The tests include a single straight

  12. Mechanisms of remodelling of small arteries, antihypertensive therapy and the immune system in hypertension.

    Science.gov (United States)

    Schiffrin, Ernesto L

    2015-12-04

    This review summarizes my lecture for the 2015 Distinguished Scientist Award from the Canadian Society of Clinical Investigation, and is based mainly on studies in my laboratory on the mechanisms of remodelling of small arteries in experimental animal and human hypertension and on treatments that lower blood pressure and improve structure and function of resistance vessels. Small resistance arteries undergo either inward eutrophic or hypertrophic remodelling, which raises blood pressure and impairs tissue perfusion. These vascular changes are corrected by some antihypertensive drugs, which may lead to improved outcomes. Vasoconstriction, growth, oxidative stress and inflammation are some of the mechanisms, within the vascular wall, that can be beneficially affected by antihypertensive agents. These antihypertensive-sensitive mechanisms are reviewed in this review, together with the inflammatory and immune mechanisms that may participate in hypertension and associated cardiovascular injury. Molecular studies, based on this research, will hopefully identify novel diagnostic and therapeutic targets, which will improve our ability to prevent and treat hypertension and cardiovascular disease.

  13. Bone marrow blood vessel ossification and "microvascular dead space" in rat and human long bone.

    Science.gov (United States)

    Prisby, Rhonda D

    2014-07-01

    Severe calcification of the bone microvascular network was observed in rats, whereby the bone marrow blood vessels appeared ossified. This study sought to characterize the magnitude of ossification in relation to patent blood vessels and adipocyte content in femoral diaphyses. Additionally, this study confirmed the presence of ossified vessels in patients with arteriosclerotic vascular disease and peripheral vascular disease and cellulitis. Young (4-6 month; n=8) and old (22-24 month; n=8) male Fischer-344 rats were perfused with barium sulfate to visualize patent bone marrow blood vessels. Femoral shafts were processed for bone histomorphometry to quantify ossified (Goldner's Trichrome) and calcified (Alizarin Red) vessels. Adipocyte content was also determined. Additional femora (n=5/age group) were scanned via μCT to quantify microvascular ossification. Bone marrow blood vessels from the rats and the human patients were also isolated and examined via microscopy. Ossified vessels (rats and humans) had osteocyte lacunae on the vessel surfaces and "normal" vessels were transitioning into bone. The volume of ossified vessels was 4800% higher (pnecrosis. Progression of bone microvascular ossification may provide the common link associated with age-related changes in bone and bone marrow. The clinical implications may be evident in the difficulties treating bone disease in the elderly. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Effect of blood vessels on light distribution in optogenetic stimulation of cortex.

    Science.gov (United States)

    Azimipour, Mehdi; Atry, Farid; Pashaie, Ramin

    2015-05-15

    In this Letter, the impact of blood vessels on light distribution during photostimulation of cortical tissue in small rodents is investigated. Brain optical properties were extracted using a double-integrating sphere setup, and optical coherence tomography was used to image cortical vessels and capillaries to generate a three-dimensional angiogram of the cortex. By combining these two datasets, a complete volumetric structure of the cortical tissue was developed and linked to a Monte Carlo code which simulates light propagation in this inhomogeneous structure and illustrates the effect of blood vessels on the penetration depth and pattern preservation in optogenetic stimulation.

  15. Development of glia and blood vessels in the internal capsule of rats.

    Science.gov (United States)

    Earle, K L; Mitrofanis, J

    1998-02-01

    We have explored two aspects of internal capsule development that have not been described previously, namely, the development of glia and of blood vessels. To these ends, we used antibodies to glial fibrillary acidic protein (GFAP) and to vimentin (to identify astrocytes and to radial glia) and Griffonia simplicifolia (lectin; to identify microglia and blood vessels). Further, we made intracardiac injections of Evans Blue to examine the permeability of this dye in the vessels of the internal capsule during neonatal development. Our results show that large numbers of radial glia, astrocytes and microglia are not labelled with these markers in the white matter of the internal capsule until about birth; very few are labelled earlier, during the critical stages of corticofugal and corticopetal axonal ingrowth (E15-E20). The large glial labelling in the internal capsule at birth is accompanied by a dense vascular innervation of the capsule; as with the glia, very few labelled patent vessels are seen earlier. After intracardiac injections of Evans Blue, we find that the blood vessels of the internal capsule are not particularly permeable to Evans Blue. At each age examined (P0, P5, P15), blood vessels are outlined very clearly and there is no diffuse haze of fluorescence within the extracellular space, which is indicative of a leaky vessel. There are three striking differences between the glial environment of the internal capsule and that of the adjacent thalamus. First, the internal capsule is never rich with radial glial fibres (vimentin- and GFAP-immunoreactive) during development (except at P0), whereas the thalamus has many radial fibres from very early development (E15-E17). Second, astrocytes (vimentin- and GFAP-immunoreactive) first become apparent in the internal capsule (E20-P0) well before they do in the thalamus (P15). Third, the internal capsule houses a large transient population of amoeboid microglia (P0-P22), whereas the thalamus does not; only ramified

  16. Blood Vessel-Derived Acellular Matrix for Vascular Graft Application

    Directory of Open Access Journals (Sweden)

    Luigi Dall’Olmo

    2014-01-01

    Full Text Available To overcome the issues connected to the use of autologous vascular grafts and artificial materials for reconstruction of small diameter (<6 mm blood vessels, this study aimed to develop acellular matrix- (AM- based vascular grafts. Rat iliac arteries were decellularized by a detergent-enzymatic treatment, whereas endothelial cells (ECs were obtained through enzymatic digestion of rat skin followed by immunomagnetic separation of CD31-positive cells. Sixteen female Lewis rats (8 weeks old received only AM or previously in vitro reendothelialized AM as abdominal aorta interposition grafts (about 1 cm. The detergent-enzymatic treatment completely removed the cellular part of vessels and both MHC class I and class II antigens. One month after surgery, the luminal surface of implanted AMs was partially covered by ECs and several platelets adhered in the areas lacking cell coverage. Intimal hyperplasia, already detected after 1 month, increased at 3 months. On the contrary, all grafts composed by AM and ECs were completely covered at 1 month and their structure was similar to that of native vessels at 3 months. Taken together, our findings show that prostheses composed of AM preseeded with ECs could be a promising approach for the replacement of blood vessels.

  17. Tracking blood vessels in human forearms using visual servoing

    DEFF Research Database (Denmark)

    Savarimuthu, Thiusius Rajeeth; Ellekilde, Lars-Peter; Hansen, Morten

    compensation. By using images taken with near-infrared light to locate the blood vessels in a human forearm and using the same images to detects movements of the arm, this paper shows that it is possible make a robot arm, potentially equipped with a needle for drawing the blood, compensate for the movements......Drawing an average of more than 2 blood sample per Danish citizen per year increases the demand for an automatic blood sampling method. This paper presents a proof of concept to one of the main challenges in making a fully automated blood sampling procedure, namely: the patient movement...

  18. Acute effect of gamma-irradiation on blood vessels of the eye

    International Nuclear Information System (INIS)

    Matsushima, Hideno

    1977-01-01

    Radiation injuries to the eye were studied by examining the alteration of fine vasculature of irradiated rabbit eyes, by referring to the usual clinical findings, fundus photography, microangiography, and histological sections. These experiments were performed by using white rabbits whose eyes were locally irradiated with a single dose of 500, 1000, 2000, 3000, and 5000 R of 60 Co-γ-ray. The eyes were observed periodically for a period up to 10 weeks after irradiation, and the following results were obtained: 1) Radiation damage to the blood vessels was maximum around 6 weeks after irradiation for doses less than 2000 R, and the damage appeared to be reversible. 2) When given more than 3000 R irradiation, alteration of the blood vessels continued increasing for 10 weeks with no evidence of recovery. Experimental evidence from these studies supports the hypothesis that the degree of radiation injury of the eye depends highly on the damage to blood vessels serving each structure of the eye. (auth.)

  19. Development of a dynamic in vitro model of a stented blood vessel to evaluate the effects of stent strut material selection and surface coating on smooth muscle cell response

    Science.gov (United States)

    Winn, Bradley Huegh

    Cardiovascular disease is the leading cause of mortality in The United States and Europe, accounting for approximately half of all deaths. The most common form of cardiovascular disease is atherosclerosis, which is characterized by the formation of fatty atheromatous plaques that can grow to occlude the vessel lumen, thus causing ischemia distal to the occlusion. This is commonly treated using balloon angioplasty, which is usually done in conjunction with the deployment of a stent. Stent deployment helps hold the vessel open following the local injury caused by balloon inflation and prevents elastic recoil and subsequent negative remodeling. Stenting has been shown to significantly reduce restenosis rates from approximately 20-50% without a stent to about 10-30% with stent deployment. However, restenosis still remains the main cause of long-term stent failure. In basic terms, a balloon angioplasty procedure is a forceful displacement of an atherosclerotic lesion serving to widen the vessel lumen to increase blood flow. This procedure causes stretching of the vessel wall, tears in the atherosclerotic plaques, and general damage to the vessel in turn signaling a complex cascade of thrombosis, inflammation, intimal thickening, and vascular remodeling. Stent deployment also further complicates the immunological response by triggering a foreign body response from the implantation of a biomaterial into the body. When performing an angioplasty procedure, particularly in conjunction with stent deployment, a certain degree of vascular injury is inevitable. However, the initial injury can be further complicated by the body's local reaction to the implanted biomaterial, the severity of which can ultimately dictate the degree of restenosis and subsequently affect procedural success. The proliferative response of VSMCs to the various afore mentioned stimuli results in the formation of often copious amounts of neointimal tissue, generally known as intimal hyperplasia. The

  20. Blood vessel damage correlated with irradiance for in vivo vascular targeted photodynamic therapy

    Science.gov (United States)

    Zhang, Jinde; Tan, Zou; Niu, Xiangyu; Lin, Linsheng; Lin, Huiyun; Li, Buhong

    2016-10-01

    Vascular targeted photodynamic therapy (V-PDT) has been widely utilized for the prevention or treatment of vascular-related diseases, including age-related macular degeneration, port-wine stains and prostate cancer. In order to quantitative assessment the blood vessel damage during V-PDT, nude mice were implanted with Titanium dorsal skin window chambers for in vivo V-PDT studies. For treatments, various irradiances including 50, 75, 100 and 200 mW/cm2 provided by a 532 nm semiconductor laser were performed with the same total light dose of 30 J/cm2 after the mice were intravenously injection of Rose Bengal for 25 mg/Kg body weight. Laser speckle imaging and microscope were used to monitor blood flow dynamics and vessel constriction during and after V-PDT, respectively. The V-PDT induced vessel damages between different groups were compared. The results show that significant difference in blood vessel damage was found between the lower irradiances (50, 75 and 100 mW/cm2) and higher irradiance (200 mW/cm2), and the blood vessel damage induced by V-PDT is positively correlated with irradiance. This study implies that the optimization of irradiance is required for enhancing V-PDT therapeutic efficiency.

  1. Mathematical modelling for trajectories of magnetic nanoparticles in a blood vessel under magnetic field

    International Nuclear Information System (INIS)

    Sharma, Shashi; Katiyar, V.K.; Singh, Uaday

    2015-01-01

    A mathematical model is developed to describe the trajectories of a cluster of magnetic nanoparticles in a blood vessel for the application of magnetic drug targeting (MDT). The magnetic nanoparticles are injected into a blood vessel upstream from a malignant tissue and are captured at the tumour site with help of an applied magnetic field. The applied field is produced by a rare earth cylindrical magnet positioned outside the body. All forces expected to significantly affect the transport of nanoparticles were incorporated, including magnetization force, drag force and buoyancy force. The results show that particles are slow down and captured under the influence of magnetic force, which is responsible to attract the magnetic particles towards the magnet. It is optimized that all particles are captured either before or at the centre of the magnet (z≤0) when blood vessel is very close proximity to the magnet (d=2.5 cm). However, as the distance between blood vessel and magnet (d) increases (above 4.5 cm), the magnetic nanoparticles particles become free and they flow away down the blood vessel. Further, the present model results are validated by the simulations performed using the finite element based COMSOL software. - Highlights: • A mathematical model is developed to describe the trajectories of magnetic nanoparticles. • The dominant magnetic, drag and buoyancy forces are considered. • All particles are captured when distance between blood vessel and magnet (d) is up to 4.5 cm. • Further increase in d value (above 4.5 cm) results the free movement of magnetic particles

  2. Imaging Blood Vessel Morphology in Skin

    DEFF Research Database (Denmark)

    Schuh, Sandra; Holmes, Jon; Ulrich, Martina

    2017-01-01

    Conventional optical coherence tomography (OCT) enables the visualization of morphological changes of skin cancer. The use of OCT in the diagnostic investigation and in the therapy decision of non-melanoma skin cancer and other skin changes is already established, and has found its way into routine...... practice. With the development of speckle-variance OCT, also named dynamic OCT (D-OCT), the vascular architecture and the blood flow of the skin can be displayed in vivo and in 3D. This novel angiographic variant of OCT offers the ability to visualize and measure vessel morphology providing a new insight...... into healthy, inflammatory and neoplastic skin lesions such as malignant melanoma. This review focuses on the possibilities of using D-OCT on healthy and diseased skin. We suggest and illustrate key diagnostic characteristics by analyzing the initial publications and preliminary unpublished data on vessel...

  3. Bone Marrow Blood Vessel Ossification and “Microvascular Dead Space” in Rat and Human Long Bone

    Science.gov (United States)

    Prisby, Rhonda D.

    2014-01-01

    Severe calcification of the bone microvascular network was observed in rats, whereby the bone marrow blood vessels appeared ossified. This study sought to characterize the magnitude of ossification in relation to patent blood vessels and adipocyte content in femoral diaphyses. Additionally, this study confirmed the presence of ossified vessels in patients with arteriosclerotic vascular disease and peripheral vascular disease and cellulitis. Young (4–6 mon; n=8) and old (22–24 mon; n=8) male Fischer-344 rats were perfused with barium sulfate to visualize patent bone marrow blood vessels. Femoral shafts were processed for bone histomorphometry to quantify ossified (Goldner’s Trichrome) and calcified (Alizarin Red) vessels. Adipocyte content was also determined. Additional femora (n=5/age group) were scanned via µCT to quantify microvascular ossification. Bone marrow blood vessels from rats and the human patients were also isolated and examined via microscopy. Ossified vessels (rats and humans) had osteocyte lacunae on the vessel surfaces and “normal” vessels were transitioning into bone. The volume of ossified vessels was 4800% higher (p necrosis. The progression of bone microvascular ossification may provide the common link associated with age-related changes in bone and bone marrow. The clinical implications may be evident in the difficulties treating bone disease in the elderly. PMID:24680721

  4. Tissue Engineering of Blood Vessels: Functional Requirements, Progress, and Future Challenges.

    Science.gov (United States)

    Kumar, Vivek A; Brewster, Luke P; Caves, Jeffrey M; Chaikof, Elliot L

    2011-09-01

    Vascular disease results in the decreased utility and decreased availability of autologus vascular tissue for small diameter (requires combined approaches from biomaterials science, cell biology, and translational medicine to develop feasible solutions with the requisite mechanical support, a non-fouling surface for blood flow, and tissue regeneration. Over the past two decades interest in blood vessel tissue engineering has soared on a global scale, resulting in the first clinical implants of multiple technologies, steady progress with several other systems, and critical lessons-learned. This review will highlight the current inadequacies of autologus and synthetic grafts, the engineering requirements for implantation of tissue-engineered grafts, and the current status of tissue-engineered blood vessel research.

  5. Regulator of calcineurin 1 mediates pathological vascular wall remodeling

    Science.gov (United States)

    Esteban, Vanesa; Méndez-Barbero, Nerea; Jesús Jiménez-Borreguero, Luis; Roqué, Mercè; Novensá, Laura; Belén García-Redondo, Ana; Salaices, Mercedes; Vila, Luis; Arbonés, María L.

    2011-01-01

    Artery wall remodeling, a major feature of diseases such as hypertension, restenosis, atherosclerosis, and aneurysm, involves changes in the tunica media mass that reduce or increase the vessel lumen. The identification of molecules involved in vessel remodeling could aid the development of improved treatments for these pathologies. Angiotensin II (AngII) is a key effector of aortic wall remodeling that contributes to aneurysm formation and restenosis through incompletely defined signaling pathways. We show that AngII induces vascular smooth muscle cell (VSMC) migration and vessel remodeling in mouse models of restenosis and aneurysm. These effects were prevented by pharmacological inhibition of calcineurin (CN) or lentiviral delivery of CN-inhibitory peptides. Whole-genome analysis revealed >1,500 AngII-regulated genes in VSMCs, with just 11 of them requiring CN activation. Of these, the most sensitive to CN activation was regulator of CN 1 (Rcan1). Rcan1 was strongly activated by AngII in vitro and in vivo and was required for AngII-induced VSMC migration. Remarkably, Rcan1−/− mice were resistant to AngII-induced aneurysm and restenosis. Our results indicate that aneurysm formation and restenosis share mechanistic elements and identify Rcan1 as a potential therapeutic target for prevention of aneurysm and restenosis progression. PMID:21930771

  6. A numerical analysis on the curved bileaflet Mechanical Heart Valve (MHV) : leaflet motion and blood flow in an elastic blood vessel

    International Nuclear Information System (INIS)

    Bang, Jin Seok; Kim, Chang Nyung; Choi, Choeng Ryul

    2005-01-01

    In blood flow passing through the Mechanical Heart Valve (MHV) and elastic blood vessel, hemolysis and platelet activation causing thrombus formation can be seen owing to the shear stress in the blood. Also, fracture and deformation of leaflets can be observed depending on the shape and material properties of the leaflets which is opened and closed in a cycle. Hence, comprehensive study is needed on the hemodynamics which is associated with the motion of leaflet and elastic blood vessel in terms of fluid-structure interaction. In this paper, a numerical analysis has been performed for a three-dimensional pulsatile blood flow associated with the elastic blood vessel and curved bileaflet for multiple cycles in light of fluid-structure interaction. From this analysis fluttering phenomenon and rebound of the leaflet have been observed and recirculation and regurgitation have been found in the flow fields of the blood. Also, the pressure distribution and the radial displacement of the elastic blood vessel have been obtained. The motion of the leaflet and flow fields of the blood have shown similar tendency compared with the previous experiments carried out in other studies. The present study can contribute to the design methodology for the curved bileaflet mechanical heart valve. Furthermore, the proposed fluid-structure interaction method will be effectively used in various fields where the interaction between fluid flow and structure are involved

  7. Pulsatile blood flow, shear force, energy dissipation and Murray's Law

    Directory of Open Access Journals (Sweden)

    Bengtsson Hans-Uno

    2006-08-01

    Full Text Available Abstract Background Murray's Law states that, when a parent blood vessel branches into daughter vessels, the cube of the radius of the parent vessel is equal to the sum of the cubes of the radii of daughter blood vessels. Murray derived this law by defining a cost function that is the sum of the energy cost of the blood in a vessel and the energy cost of pumping blood through the vessel. The cost is minimized when vessel radii are consistent with Murray's Law. This law has also been derived from the hypothesis that the shear force of moving blood on the inner walls of vessels is constant throughout the vascular system. However, this derivation, like Murray's earlier derivation, is based on the assumption of constant blood flow. Methods To determine the implications of the constant shear force hypothesis and to extend Murray's energy cost minimization to the pulsatile arterial system, a model of pulsatile flow in an elastic tube is analyzed. A new and exact solution for flow velocity, blood flow rate and shear force is derived. Results For medium and small arteries with pulsatile flow, Murray's energy minimization leads to Murray's Law. Furthermore, the hypothesis that the maximum shear force during the cycle of pulsatile flow is constant throughout the arterial system implies that Murray's Law is approximately true. The approximation is good for all but the largest vessels (aorta and its major branches of the arterial system. Conclusion A cellular mechanism that senses shear force at the inner wall of a blood vessel and triggers remodeling that increases the circumference of the wall when a shear force threshold is exceeded would result in the observed scaling of vessel radii described by Murray's Law.

  8. Proteomic profiling of tissue-engineered blood vessel walls constructed by adipose-derived stem cells.

    Science.gov (United States)

    Wang, Chen; Guo, Fangfang; Zhou, Heng; Zhang, Yun; Xiao, Zhigang; Cui, Lei

    2013-02-01

    Adipose-derived stem cells (ASCs) can differentiate into smooth muscle cells and have been engineered into elastic small diameter blood vessel walls in vitro. However, the mechanisms involved in the development of three-dimensional (3D) vascular tissue remain poorly understood. The present study analyzed protein expression profiles of engineered blood vessel walls constructed by human ASCs using methods of two-dimensional gel electrophoresis (2DE) and mass spectrometry (MS). These results were compared to normal arterial walls. A total of 1701±15 and 1265±26 protein spots from normal and engineered blood vessel wall extractions were detected by 2DE, respectively. A total of 20 spots with at least 2.0-fold changes in expression were identified, and 38 differently expressed proteins were identified by 2D electrophoresis and ion trap MS. These proteins were classified into seven functional categories: cellular organization, energy, signaling pathway, enzyme, anchored protein, cell apoptosis/defense, and others. These results demonstrated that 2DE, followed by ion trap MS, could be successfully utilized to characterize the proteome of vascular tissue, including tissue-engineered vessels. The method could also be employed to achieve a better understanding of differentiated smooth muscle protein expression in vitro. These results provide a basis for comparative studies of protein expression in vascular smooth muscles of different origin and could provide a better understanding of the mechanisms of action needed for constructing blood vessels that exhibit properties consistent with normal blood vessels.

  9. PDGFRα plays a crucial role in connective tissue remodeling.

    Science.gov (United States)

    Horikawa, Shinjiro; Ishii, Yoko; Hamashima, Takeru; Yamamoto, Seiji; Mori, Hisashi; Fujimori, Toshihiko; Shen, Jie; Inoue, Ran; Nishizono, Hirofumi; Itoh, Hiroshi; Majima, Masataka; Abraham, David; Miyawaki, Toshio; Sasahara, Masakiyo

    2015-12-07

    Platelet derived growth factor (PDGF) plays a pivotal role in the remodeling of connective tissues. Emerging data indicate the distinctive role of PDGF receptor-α (PDGFRα) in this process. In the present study, the Pdgfra gene was systemically inactivated in adult mouse (α-KO mouse), and the role of PDGFRα was examined in the subcutaneously implanted sponge matrices. PDGFRα expressed in the fibroblasts of Pdgfra-preserving control mice (Flox mice), was significantly reduced in the sponges in α-KO mice. Neovascularized areas were largely suppressed in the α-KO mice than in the Flox mice, whereas the other parameters related to the blood vessels and endothelial cells were similar. The deposition of collagen and fibronectin and the expression of collagen 1a1 and 3a1 genes were significantly reduced in α-KO mice. There was a significantly decrease in the number and dividing fibroblasts in the α-KO mice, and those of macrophages were similar between the two genotypes. Hepatocyte growth factor (Hgf) gene expression was suppressed in Pdgfra-inactivated fibroblasts and connective tissue. The findings implicate the role of PDGFRα-dependent ECM and HGF production in fibroblasts that promotes the remodeling of connective tissue and suggest that PDGFRα may be a relevant target to regulate connective tissue remodeling.

  10. AGE-RELATED FEATURES OF PERIPHERAL BLOOD MARKERS IN CHILDREN AND YOUNG ADULTS WITH NORMAL AND PATHOLOGICAL REMODELING OF BONE TISSUE

    Directory of Open Access Journals (Sweden)

    M. V. Dvornichenko

    2016-01-01

    Full Text Available Activities of total alkaline phosphatase (TALP and its bone isoform (BALP was greater in groups of children and adolescents in the late posttraumatic period (pattern of reparative bone remodeling and scoliosis (pathological bone remodeling, than in the control (healthy children and adolescents. The content of collagen type I degradation products (CrossLaps peripheral blood practically was unchanged. Examined group with posttraumatic period had high activity of tartrate-resistant acid phosphatase form (TRACP. TALP activity reached minimum values in all the studied groups. In the process of children growing to 15–18 years old, as compared to 7–10 years old, reducing activity of remodeling was observed under physiological (healthy donors and reparative osteogenesis. It’s changes was recorded by significant decrease of the studied indicators. On the contrary, children 15–18 years old with scoliosis had maximum of the imbalance (activation/inhibition of various signs of osteogenesis of resorptive/synthetic bone processes. Also, for this group we discovered decrease osteocalcin concentration of 4 times in comparison with the group children of 7–10 years old. The detected growth of the correlations number in the correlation matrix of bone remodeling markers in case of scoliosis proposes the reduction of adaptation reserve of 15–18 years old adolescents, suffering from dysplasia of connective tissue. Thus, the pathophysiological and clinical significance of distant markers of bone metabolism screening in peripheral blood the is ambiguous. The interpretation of these indicators is difficult and largely depends on the clinical situation and age of patients. This requires improving the diagnostic approach to assess physiological and pathological remodeling of bone tissue by means of biochemical blood indicators. 

  11. Classic beta-amyloid deposits cluster around large diameter blood vessels rather than capillaries in sporadic Alzheimer's disease.

    Science.gov (United States)

    Armstrong, Richard A

    2006-11-01

    Various hypotheses could explain the relationship between beta-amyloid (Abeta) deposition and the vasculature in Alzheimer's disease (AD). Amyloid deposition may reduce capillary density, affect endothelial cells of blood vessels, result in diffusion from blood vessels, or interfere with the perivascular clearance mechanism. Hence, the spatial pattern of the classic ('cored') type of Abeta deposit was studied in the upper laminae (I,II/III) of the superior frontal gyrus in nine cases of sporadic AD (SAD). Sections were immunostained with antibodies against Abeta and with collagen IV to study the relationships between the spatial distribution of the classic deposits and the blood vessel profiles. Both the classic deposits and blood vessel profiles were distributed in clusters. In all cases, there was a positive spatial correlation between the clusters of the classic deposits and the larger diameter (>10 microm) blood vessel profiles and especially the vertically penetrating arterioles. In only 1 case, was there a significant spatial correlation between the clusters of the classic deposits and the smaller diameter (upper laminae of the frontal cortex. This aggregation could result from diffusion of proteins from blood vessels or from overloading the system of perivascular clearance from the brain.

  12. Optics based signal processing methods for intraoperative blood vessel detection and quantification in real time (Conference Presentation)

    Science.gov (United States)

    Chaturvedi, Amal; Shukair, Shetha A.; Le Rolland, Paul; Vijayvergia, Mayank; Subramanian, Hariharan; Gunn, Jonathan W.

    2016-03-01

    Minimally invasive operations require surgeons to make difficult cuts to blood vessels and other tissues with impaired tactile and visual feedback. This leads to inadvertent cuts to blood vessels hidden beneath tissue, causing serious health risks to patients and a non-reimbursable financial burden to hospitals. Intraoperative imaging technologies have been developed, but these expensive systems can be cumbersome and provide only a high-level view of blood vessel networks. In this research, we propose a lean reflectance-based system, comprised of a dual wavelength LED, photodiode, and novel signal processing algorithms for rapid vessel characterization. Since this system takes advantage of the inherent pulsatile light absorption characteristics of blood vessels, no contrast agent is required for its ability to detect the presence of a blood vessel buried deep inside any tissue type (up to a cm) in real time. Once a vessel is detected, the system is able to estimate the distance of the vessel from the probe and the diameter size of the vessel (with a resolution of ~2mm), as well as delineate the type of tissue surrounding the vessel. The system is low-cost, functions in real-time, and could be mounted on already existing surgical tools, such as Kittner dissectors or laparoscopic suction irrigation cannulae. Having been successfully validated ex vivo, this technology will next be tested in a live porcine study and eventually in clinical trials.

  13. Estimation of vessel diameter and blood flow dynamics from laser speckle images

    DEFF Research Database (Denmark)

    Postnov, Dmitry D.; Tuchin, Valery V.; Sosnovtseva, Olga

    2016-01-01

    Laser speckle imaging is a rapidly developing method to study changes of blood velocity in the vascular networks. However, to assess blood flow and vascular responses it is crucial to measure vessel diameter in addition to blood velocity dynamics. We suggest an algorithm that allows for dynamical...

  14. Computational Fluid Dynamics Analysis of Pulsatile Blood Flow Behavior in Modelled Stenosed Vessels with Different Severities

    Directory of Open Access Journals (Sweden)

    Mohsen Mehrabi

    2012-01-01

    Full Text Available This study focuses on the behavior of blood flow in the stenosed vessels. Blood is modelled as an incompressible non-Newtonian fluid which is based on the power law viscosity model. A numerical technique based on the finite difference method is developed to simulate the blood flow taking into account the transient periodic behaviour of the blood flow in cardiac cycles. Also, pulsatile blood flow in the stenosed vessel is based on the Womersley model, and fluid flow in the lumen region is governed by the continuity equation and the Navier-Stokes equations. In this study, the stenosis shape is cosine by using Tu and Devil model. Comparing the results obtained from three stenosed vessels with 30%, 50%, and 75% area severity, we find that higher percent-area severity of stenosis leads to higher extrapressure jumps and higher blood speeds around the stenosis site. Also, we observe that the size of the stenosis in stenosed vessels does influence the blood flow. A little change on the cross-sectional value makes vast change on the blood flow rate. This simulation helps the people working in the field of physiological fluid dynamics as well as the medical practitioners.

  15. An Experimental Study to Replace the Thoracic Descending Aorta for Pigs with a Self-Made Sutureless Blood Vessel

    Directory of Open Access Journals (Sweden)

    Fenglin Song

    2014-01-01

    Full Text Available To simplify the procedure of blood vessel replacement operation and shorten the vascular anastomosis time, we developed a special artificial blood vessel which can be connected to native blood vessels without suture. The self-made sutureless blood vessel (SMSBV was made from two titanium connectors and a Gore-Tex graft. To investigate blood compatibility and histocompatibility of the SMSBV, we carried thoracic descending aorta replacement using either SMSBV or Gore-Tex, respectively, in pigs. The aortic clamp time and the operative blood loss in the experimental group (using SMSBV were less than those in the control group (using Gore-Tex. The whole blood hematocrit, platelet count, plasma soluble P-selectin, plasma free hemoglobin, and interleukins 2, 6 at each time point were not different significantly between the two groups. Light microscopy and transmission electron microscopy examination showed there were layers of vascular smooth muscle cells and endothelial cells adhered in the inner wall of artificial blood vessel without any signs of thrombosis. Based on the result, we have drawn the conclusion that the application of SMSBV can significantly shorten the vascular anastomosis time, reduce operative blood loss, and show good blood and tissue compatibility.

  16. Continuum mathematical modelling of pathological growth of blood vessels

    Science.gov (United States)

    Stadnik, N. E.; Dats, E. P.

    2018-04-01

    The present study is devoted to the mathematical modelling of a human blood vessel pathological growth. The vessels are simulated as the thin-walled circular tube. The boundary value problem of the surface growth of an elastic thin-walled cylinder is solved. The analytical solution is obtained in terms of velocities of stress strain state parameters. The condition of thinness allows us to study finite displacements of cylinder surfaces by means of infinitesimal deformations. The stress-strain state characteristics, which depend on the mechanical parameters of the biological processes, are numerically computed and graphically analysed.

  17. Waves and fluid-solid interaction in stented blood vessels

    Science.gov (United States)

    Frecentese, S.; Argani, L. P.; Movchan, A. B.; Movchan, N. V.; Carta, G.; Wall, M. L.

    2018-01-01

    This paper focuses on the modelling of fluid-structure interaction and wave propagation problems in a stented artery. Reflection of waves in blood vessels is well documented in the literature, but it has always been linked to a strong variation in geometry, such as the branching of vessels. The aim of this work is to detect the possibility of wave reflection in a stented artery due to the repetitive pattern of the stents. The investigation of wave propagation and possible blockages under time-harmonic conditions is complemented with numerical simulations in the transient regime.

  18. Automatic segmentation of blood vessels from retinal fundus images ...

    Indian Academy of Sciences (India)

    The retinal blood vessels were segmented through color space conversion and color channel extraction, image pre-processing, Gabor filtering, image postprocessing, feature construction through application of principal component analysis, k-means clustering and first level classification using Naïve–Bayes classification ...

  19. Fluid Dynamics of Magnetic Nanoparticles in Simulated Blood Vessels

    Science.gov (United States)

    Blue, Lauren; Sewell, Mary Kathryn; Brazel, Christopher S.

    2008-11-01

    Magnetic nanoparticles (MNPs) can be used to locally target therapies and offer the benefit of using an AC magnetic field to combine hyperthermia treatment with the triggered release of therapeutic agents. Here, we investigate localization of MNPs in a simulated environment to understand the relationship between magnetic field intensity and bulk fluid dynamics to determine MNP retention in a simulated blood vessel. As MNPs travel through blood vessels, they can be slowed or trapped in a specific area by applying a magnetic field. Magnetic cobalt ferrite nanoparticles were synthesized and labeled with a fluorescent rhodamine tag to visualize patterns in a flow cell, as monitored by a fluorescence microscope. Particle retention was determined as a function of flow rate, concentration, and magnetic field strength. Understanding the relationship between magnetic field intensity, flow behavior and nanoparticle characteristics will aid in the development of therapeutic systems specifically targeted to diseased tissue.

  20. DLC coating of textile blood vessels using PLD

    Czech Academy of Sciences Publication Activity Database

    Kocourek, Tomáš; Jelínek, Miroslav; Vorlíček, Vladimír; Zemek, Josef; Janča, T.; Žížková, V.; Podlaha, J.; Popov, C.

    2008-01-01

    Roč. 93, č. 3 (2008), s. 627-632 ISSN 0947-8396 R&D Projects: GA MPO FI-IM2/068; GA ČR GA202/06/0216 Institutional research plan: CEZ:AV0Z10100522 Keywords : blood vessels * PLD * DLC * sp2 * sp3 Subject RIV: BH - Optics, Masers, Lasers Impact factor: 1.884, year: 2008

  1. Application of blood-pool agents in visualization of peripheral vessels

    International Nuclear Information System (INIS)

    Giovagnoni, A.; Catalano, C.

    2007-01-01

    Effective arterial imaging is essential in patients with peripheral arterial disease (PAD) in whom a revascularization procedure is planned. Digital subtraction angiography (DSA) has traditionally been regarded as the gold standard for imaging in peripheral arterial disease, but this technique is subject to certain limitations, such as the risks of adverse reactions associated with arterial catheterization and iodinated contrast agents. Contrast-enhanced magnetic resonance angiography is now recommended as an effective and useful imaging technique in peripheral arterial disease, since it offers high enhanced contrast between blood and stationary tissue and fast acquisition times. However, extracellular gadolinium contrast agents rapidly diffuse into the interstitial spaces, and thus are suitable only for first-pass imaging. This limitation can be overcome by the use of blood-pool (intravascular) contrast agents, such as gadofosveset trisodium (Vasovist, Bayer Schering Pharma AG, Berlin, Germany), which are retained within the blood vessels and hence facilitate both first-pass and steady-state imaging with high spatial resolution. Blood-pool agents, therefore, offer improved imaging, particularly of distal vessels, compared with extracellular contrast agents. Examples of first-pass and steady-state imaging with gadofosveset are presented. (orig.)

  2. Establishment of an animal model of mice with radiation- injured soft tissue blood vessels

    International Nuclear Information System (INIS)

    Wang Daiyou; Yu Dahai; Wu Jiaxiao; Wei Shanliang; Wen Yuming

    2004-01-01

    Objective: The aim of this study was to establish an animal model of mice with radiation-injured soft tissue blood vessels. Methods: Forty male mice were irradiated with 30 Gy on the right leg. After the irradiation was finished each of the 40 male mice was tested with angiography, and its muscle tissues on the bilateral legs were examined with vessel staining assay and electron microscopy. Results: The results showed that the number of vessels on the right leg was less than that on the left leg, the microvessel density, average diameter and average sectional area of the right leg were all lower than those of the left, and the configuration and ultra-structure of vessels were also different between both sides of legs. Conclusion: In the study authors successfully established an animal model of mice with radiation-injured soft tissue blood vessels

  3. Mouse lung contains endothelial progenitors with high capacity to form blood and lymphatic vessels

    Directory of Open Access Journals (Sweden)

    Barleon Bernhard

    2010-07-01

    Full Text Available Abstract Background Postnatal endothelial progenitor cells (EPCs have been successfully isolated from whole bone marrow, blood and the walls of conduit vessels. They can, therefore, be classified into circulating and resident progenitor cells. The differentiation capacity of resident lung endothelial progenitor cells from mouse has not been evaluated. Results In an attempt to isolate differentiated mature endothelial cells from mouse lung we found that the lung contains EPCs with a high vasculogenic capacity and capability of de novo vasculogenesis for blood and lymph vessels. Mouse lung microvascular endothelial cells (MLMVECs were isolated by selection of CD31+ cells. Whereas the majority of the CD31+ cells did not divide, some scattered cells started to proliferate giving rise to large colonies (> 3000 cells/colony. These highly dividing cells possess the capacity to integrate into various types of vessels including blood and lymph vessels unveiling the existence of local microvascular endothelial progenitor cells (LMEPCs in adult mouse lung. EPCs could be amplified > passage 30 and still expressed panendothelial markers as well as the progenitor cell antigens, but not antigens for immune cells and hematopoietic stem cells. A high percentage of these cells are also positive for Lyve1, Prox1, podoplanin and VEGFR-3 indicating that a considerabe fraction of the cells are committed to develop lymphatic endothelium. Clonogenic highly proliferating cells from limiting dilution assays were also bipotent. Combined in vitro and in vivo spheroid and matrigel assays revealed that these EPCs exhibit vasculogenic capacity by forming functional blood and lymph vessels. Conclusion The lung contains large numbers of EPCs that display commitment for both types of vessels, suggesting that lung blood and lymphatic endothelial cells are derived from a single progenitor cell.

  4. Vascular Remodelling and Mesenchymal Transition in Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Pier Andrea Nicolosi

    2016-01-01

    Full Text Available Fibrosis of the skin and of internal organs, autoimmunity, and vascular inflammation are hallmarks of Systemic Sclerosis (SSc. The injury and activation of endothelial cells, with hyperplasia of the intima and eventual obliteration of the vascular lumen, are early features of SSc. Reduced capillary blood flow coupled with deficient angiogenesis leads to chronic hypoxia and tissue ischemia, enforcing a positive feed-forward loop sustaining vascular remodelling, further exacerbated by extracellular matrix accumulation due to fibrosis. Despite numerous developments and a growing number of controlled clinical trials no treatment has been shown so far to alter SSc natural history, outlining the need of further investigation in the molecular pathways involved in the pathogenesis of the disease. We review some processes potentially involved in SSc vasculopathy, with attention to the possible effect of sustained vascular inflammation on the plasticity of vascular cells. Specifically we focus on mesenchymal transition, a key phenomenon in the cardiac and vascular development as well as in the remodelling of injured vessels. Recent work supports the role of transforming growth factor-beta, Wnt, and Notch signaling in these processes. Importantly, endothelial-mesenchymal transition may be reversible, possibly offering novel cues for treatment.

  5. The efficiency of laser radiation absorption by hemoglobin and oxyhemoglobin in the skin blood vessels

    International Nuclear Information System (INIS)

    Asimov, M.; Asimov, R.; Gisbrecht, A.

    1999-01-01

    The results of the investigation of the efficiency of light absorption by oxyhemoglobin (HbO 2 ) and deoxyhemoglobin (Hb) in cutaneous blood vessels in dependence on the radiation wavelength and the optical properties of the tissue is presented. Using the Kubelka - Munk optical model of the tissue the spectral dependence of the efficiency of laser interaction both on HbO 2 and Hb of blood vessels at different depths of the tissue layer are calculated. The obtained results show that for blood vessels located in tissue up to a depth of 2500 μm the efficiency of laser radiation absorption follows the shape of the Q -absorption bands of HbO 2 and Hb

  6. Simulative study on dose distribution of 103Pd stent in blood-vessel

    International Nuclear Information System (INIS)

    Yuan Shuyu; Dai Guangfu; Xu Zhiyong; Sun Fuyin; Xu Shuhe; Ma Fengwu

    2003-01-01

    Objective: To evaluate the dose distribution of 103 Pd stent in the blood-vessel. Methods: Simulative study on dose distribution of endovascular 103 Pd stent was conducted with thermoluminescence dosimeter. The vessel wall was substituted by muscle equivalent material in this simulative study. Results: When radioactivity of the study 103 Pd stent was 9.8 MBq the absorbed dose from the stent surface by muscle equivalent material was 9.8 Gy at 17 d (the half-life period of 103 Pd). The radioactivity of 103 Pd stent surface rapidly attenuated over the radial distance. 80% of the radioactivity at the area that was radially 0.4 mm apart from the stent surface was absorbed by the simulative blood-vessel wall. Conclusion: Endovascular 103 Pd stent does not exert significant injury on the surrounding organs or tissues

  7. 3-D segmentation of retinal blood vessels in spectral-domain OCT volumes of the optic nerve head

    Science.gov (United States)

    Lee, Kyungmoo; Abràmoff, Michael D.; Niemeijer, Meindert; Garvin, Mona K.; Sonka, Milan

    2010-03-01

    Segmentation of retinal blood vessels can provide important information for detecting and tracking retinal vascular diseases including diabetic retinopathy, arterial hypertension, arteriosclerosis and retinopathy of prematurity (ROP). Many studies on 2-D segmentation of retinal blood vessels from a variety of medical images have been performed. However, 3-D segmentation of retinal blood vessels from spectral-domain optical coherence tomography (OCT) volumes, which is capable of providing geometrically accurate vessel models, to the best of our knowledge, has not been previously studied. The purpose of this study is to develop and evaluate a method that can automatically detect 3-D retinal blood vessels from spectral-domain OCT scans centered on the optic nerve head (ONH). The proposed method utilized a fast multiscale 3-D graph search to segment retinal surfaces as well as a triangular mesh-based 3-D graph search to detect retinal blood vessels. An experiment on 30 ONH-centered OCT scans (15 right eye scans and 15 left eye scans) from 15 subjects was performed, and the mean unsigned error in 3-D of the computer segmentations compared with the independent standard obtained from a retinal specialist was 3.4 +/- 2.5 voxels (0.10 +/- 0.07 mm).

  8. Neutrophil-Mediated Delivery of Therapeutic Nanoparticles across Blood Vessel Barrier for Treatment of Inflammation and Infection.

    Science.gov (United States)

    Chu, Dafeng; Gao, Jin; Wang, Zhenjia

    2015-12-22

    Endothelial cells form a monolayer in lumen of blood vessels presenting a great barrier for delivery of therapeutic nanoparticles (NPs) into extravascular tissues where most diseases occur, such as inflammation disorders and infection. Here, we report a strategy for delivering therapeutic NPs across this blood vessel barrier by nanoparticle in situ hitchhiking activated neutrophils. Using intravital microscopy of TNF-α-induced inflammation of mouse cremaster venules and a mouse model of acute lung inflammation, we demonstrated that intravenously (iv) infused NPs made from denatured bovine serum albumin (BSA) were specifically internalized by activated neutrophils, and subsequently, the neutrophils containing NPs migrated across blood vessels into inflammatory tissues. When neutrophils were depleted using anti-Gr-1 in a mouse, the transport of albumin NPs across blood vessel walls was robustly abolished. Furthermore, it was found that albumin nanoparticle internalization did not affect neutrophil mobility and functions. Administration of drug-loaded albumin NPs markedly mitigated the lung inflammation induced by LPS (lipopolysaccharide) or infection by Pseudomonas aeruginosa. These results demonstrate the use of an albumin nanoparticle platform for in situ targeting of activated neutrophils for delivery of therapeutics across the blood vessel barriers into diseased sites. This study demonstrates our ability to hijack neutrophils to deliver nanoparticles to targeted diseased sites.

  9. "Sausage-string" appearance of arteries and arterioles can be caused by an instability of the blood vessel wall

    DEFF Research Database (Denmark)

    Jacobsen, Jens Christian Brings; Beierholm, Ulrik; Mikkelsen, Rene

    2002-01-01

    Vascular damage induced by acute hypertension is preceded by a peculiar pattern where blood vessels show alternating regions of constrictions and dilations ("sausages on a string"). The pattern occurs in the smaller blood vessels, and it plays a central role in causing the vascular damage. A rela...... phenomenon. Experimental data suggest that the structural changes induced by the instability may cause secondary damage to the wall of small arteries and arterioles in the form of endothelial hyperpermeability followed by local fibrinoid necrosis of the vascular wall.......Vascular damage induced by acute hypertension is preceded by a peculiar pattern where blood vessels show alternating regions of constrictions and dilations ("sausages on a string"). The pattern occurs in the smaller blood vessels, and it plays a central role in causing the vascular damage....... A related vascular pattern has been observed in larger vessels from several organs during angiography. In the larger vessels the occurrence of the pattern does not appear to be related to acute hypertension. A unifying feature between the phenomenon in large and small vessels seems to be an increase...

  10. MACROMICROSCOPIC AND ULTRAMICROSCOPIC CHARACTERISTICS OF THE HART AND ITS BLOOD VESSELS IN MICE EHRLICHIOSIS INFECTION

    Directory of Open Access Journals (Sweden)

    Pokhil S. I.

    2013-12-01

    Full Text Available The macromicroscopic, ultramicroscopic studying change’s in the hart and its blood vessels in unlinear immunocomprometive laboratory male and female mice with the experimental ehrlichiosis is presented in this article. The cardiac destructive and degenerative changes,cardiomyopathy, cardiosclerosis had been established inexperimental animal group’s. The blood vessels endothelial lieyr disorganization, stasis, thrombosis has been noted.

  11. An experimental system for the study of ultrasound exposure of isolated blood vessels

    NARCIS (Netherlands)

    Tokarczyk, Anna; Rivens, Ian; van Bavel, E.; Symonds-Tayler, Richard; ter Haar, Gail

    2013-01-01

    An experimental system designed for the study of the effects of diagnostic or therapeutic ultrasound exposure on isolated blood vessels in the presence or absence of intraluminal contrast agent is described. The system comprised several components. A microscope was used to monitor vessel size (and

  12. Theoretical evaluations of magnetic nanoparticle-enhanced heating on tumor embedded with large blood vessels during hyperthermia

    International Nuclear Information System (INIS)

    Wang, Q.; Deng, Z. S.; Liu, J.

    2012-01-01

    The large blood vessels surrounding the tumor would significantly result in heat sink, and thus seriously limit the thermal ablative area during tumor hyperthermia. Magnetic nanoparticle (MNP) was recently identified as an important heating enhancer to improve the treatment efficiency. It will not only help to absorb more energy under the irradiation of external magnetic field, but also can block the blood flow and subsequently weaken the heat sink effect of large vessels. In this study, these two critical factors, reserved to be undisclosed before in theory, were comprehensively investigated through three-dimensional numerical simulation. The results suggested that concerning the contribution to temperature increase in the tissues surrounding large vessel, the factor of blood flow blocking is more effective than that of energy absorption. Therefore, selective loading of MNPs to the target sites is expected to serve as a promising method to perform successful hyperthermia treatment for tumor tissues embedded with large blood vessels.

  13. Theoretical evaluations of magnetic nanoparticle-enhanced heating on tumor embedded with large blood vessels during hyperthermia

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Q. [Tsinghua University, Department of Biomedical Engineering, School of Medicine (China); Deng, Z. S. [Chinese Academy of Sciences, Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry (China); Liu, J., E-mail: jliubme@tsinghua.edu.cn [Tsinghua University, Department of Biomedical Engineering, School of Medicine (China)

    2012-07-15

    The large blood vessels surrounding the tumor would significantly result in heat sink, and thus seriously limit the thermal ablative area during tumor hyperthermia. Magnetic nanoparticle (MNP) was recently identified as an important heating enhancer to improve the treatment efficiency. It will not only help to absorb more energy under the irradiation of external magnetic field, but also can block the blood flow and subsequently weaken the heat sink effect of large vessels. In this study, these two critical factors, reserved to be undisclosed before in theory, were comprehensively investigated through three-dimensional numerical simulation. The results suggested that concerning the contribution to temperature increase in the tissues surrounding large vessel, the factor of blood flow blocking is more effective than that of energy absorption. Therefore, selective loading of MNPs to the target sites is expected to serve as a promising method to perform successful hyperthermia treatment for tumor tissues embedded with large blood vessels.

  14. Modification method to reduce the impact of blood vessel on noncontact discrimination of human blood based on ;M+N; theory

    Science.gov (United States)

    Zhang, Linna; Ding, Hongyan; Lin, Ling; Wang, Yimin; Guo, Xin

    2018-01-01

    Noncontact discriminating human blood is significantly crucial for import-export ports and inspection and quarantine departments. We had already demonstrated that visible diffuse reflectance spectroscopy combining PLS-DA method can successfully realize noncontact human blood discrimination. However, the circulated blood vessels may be produced with different materials. The use of various kinds of blood tubes may have a negative effect on the discrimination, based on ;M+N; theory (Li et al., 2016). In this research, we explored the impact of different material of blood vessels, such as glass tube and plastic tube, on the prediction ability of the discrimination model. Furthermore, we searched for the modification method to reduce the influence from the blood tubes. Our work indicated that generalized diffuse reflectance method can greatly improve the discrimination accuracy. This research can greatly facilitate the application of noncontact discrimination method based on visible and near-infrared diffuse reflectance spectroscopy.

  15. Segmentation of retinal blood vessels using artificial neural networks for early detection of diabetic retinopathy

    Science.gov (United States)

    Mann, Kulwinder S.; Kaur, Sukhpreet

    2017-06-01

    There are various eye diseases in the patients suffering from the diabetes which includes Diabetic Retinopathy, Glaucoma, Hypertension etc. These all are the most common sight threatening eye diseases due to the changes in the blood vessel structure. The proposed method using supervised methods concluded that the segmentation of the retinal blood vessels can be performed accurately using neural networks training. It uses features which include Gray level features; Moment Invariant based features, Gabor filtering, Intensity feature, Vesselness feature for feature vector computation. Then the feature vector is calculated using only the prominent features.

  16. A three-temperature model of selective photothermolysis for laser treatment of port wine stain containing large malformed blood vessels

    International Nuclear Information System (INIS)

    Li, D.; Wang, G.X.; He, Y.L.; Wu, W.J.; Chen, B.

    2014-01-01

    As congenital vascular malformations, port wine stain (PWS) is composed of ectatic venular capillary blood vessels buried within healthy dermis. In clinic, pulsed dye laser (PDL) in visible band (e.g. 585 nm) together with cryogen spray cooling (CSC) have become the golden standard for treatment of PWS. However, due to the limited energy deposition of the PDL in blood, large blood vessels are likely to survive from the laser irradiation. As a result, complete clearance of the lesions is rarely achieved. Assuming the local thermal non-equilibrium in skin tissue during the laser surgery, a three-temperature model is proposed to treat the PWS tissue as a porous media composed of a non-absorbing dermal matrix buried with the blood as well as the large malformed blood vessels. Three energy equations are constructed and solved coupling for the temperature of the blood in average-sized PWS vessels, non-absorbing dermal tissues and large malformed blood vessels, respectively. Subsequently, the thermal responses of human skin to visible (585 nm) and near-infrared (1064 nm) laser irradiations with various pulse durations in conjunction with cryogen spray cooling are investigated by the new model, and Arrhenius integral is used to analyze the thermal damage. The simulations show that the short pulse duration of 1.5 ms results in a higher selective heating of blood over epidermis, which will lead to a desired clinic outcome than the longer pulse duration. Due to a much deeper light penetration depth, laser irradiation with 1064 nm in wavelength is superior to that with 585 nm in treating patients with cutaneous hyper-vascular malformation. Complete coagulations are predicted in large-sized and deeply extending blood vessels by 1064 nm laser. - Highlights: •A three-temperature model is proposed for the laser treatment of port wine stain (PWS). •Average sized and large malformed blood vessels in porous medium (tissue) are considered. •Thermal responses of PWS to

  17. Does Receiving a Blood Transfusion Predict for Length of Stay in Children Undergoing Cranial Vault Remodeling for Craniosynostosis? Outcomes Using the Pediatric National Surgical Quality Improvement Program Dataset.

    Science.gov (United States)

    Markiewicz, Michael R; Alden, Tord; Momin, Mohmed Vasim; Olsson, Alexis B; Jurado, Ray J; Abdullah, Fizan; Miloro, Michael

    2017-08-01

    Recent interventions have aimed at reducing the need for blood transfusions in the perioperative period in patients with craniosynostosis undergoing cranial vault remodeling. However, little is known regarding whether the receipt of a blood transfusion influences the length of hospital stay. The purpose of this study was to assess whether the receipt of a blood transfusion in patients undergoing cranial vault remodeling is associated with an increased length of stay. To address the research purposes, we designed a retrospective cohort study using the 2014 Pediatric National Surgical Quality Improvement Program (NSQIP Peds) dataset. The primary predictor variable was whether patients received a blood transfusion during cranial vault remodeling. The primary outcome variable was length of hospital stay after the operation. The association between the receipt of blood transfusions and length of stay was assessed using the Student t test. The association between other covariates and the outcome variable was assessed using linear regression, analysis of variance, and the Tukey test for post hoc pair-wise comparisons. The sample was composed of 756 patients who underwent cranial vault remodeling: 503 who received blood transfusions and 253 who did not. The primary predictor variable of blood transfusion was associated with an increased length of stay (4.1 days vs 3.0 days, P = .03). Other covariates associated with an increased length of stay included race, American Society of Anesthesiologists status, premature birth, presence of a congenital malformation, and number of sutures involved in craniosynostosis. The receipt of a blood transfusion in the perioperative period in patients with craniosynostosis undergoing cranial vault remodeling was associated with an increased length of stay. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  18. VESsel GENeration Analysis (VESGEN): Innovative Vascular Mappings for Astronaut Exploration Health Risks and Human Terrestrial Medicine

    Science.gov (United States)

    Parsons-Wingerter, Patricia; Kao, David; Valizadegan, Hamed; Martin, Rodney; Murray, Matthew C.; Ramesh, Sneha; Sekaran, Srinivaas

    2017-01-01

    Currently, astronauts face significant health risks in future long-duration exploration missions such as colonizing the Moon and traveling to Mars. Numerous risks include greatly increased radiation exposures beyond the low earth orbit (LEO) of the ISS, and visual and ocular impairments in response to microgravity environments. The cardiovascular system is a key mediator in human physiological responses to radiation and microgravity. Moreover, blood vessels are necessarily involved in the progression and treatment of vascular-dependent terrestrial diseases such as cancer, coronary vessel disease, wound-healing, reproductive disorders, and diabetes. NASA developed an innovative, globally requested beta-level software, VESsel GENeration Analysis (VESGEN) to map and quantify vascular remodeling for application to astronaut and terrestrial health challenges. VESGEN mappings of branching vascular trees and networks are based on a weighted multi-parametric analysis derived from vascular physiological branching rules. Complex vascular branching patterns are determined by biological signaling mechanisms together with the fluid mechanics of multi-phase laminar blood flow.

  19. Retinal blood vessel extraction using tunable bandpass filter and fuzzy conditional entropy.

    Science.gov (United States)

    Sil Kar, Sudeshna; Maity, Santi P

    2016-09-01

    Extraction of blood vessels on retinal images plays a significant role for screening of different opthalmologic diseases. However, accurate extraction of the entire and individual type of vessel silhouette from the noisy images with poorly illuminated background is a complicated task. To this aim, an integrated system design platform is suggested in this work for vessel extraction using a sequential bandpass filter followed by fuzzy conditional entropy maximization on matched filter response. At first noise is eliminated from the image under consideration through curvelet based denoising. To include the fine details and the relatively less thick vessel structures, the image is passed through a bank of sequential bandpass filter structure optimized for contrast enhancement. Fuzzy conditional entropy on matched filter response is then maximized to find the set of multiple optimal thresholds to extract the different types of vessel silhouettes from the background. Differential Evolution algorithm is used to determine the optimal gain in bandpass filter and the combination of the fuzzy parameters. Using the multiple thresholds, retinal image is classified as the thick, the medium and the thin vessels including neovascularization. Performance evaluated on different publicly available retinal image databases shows that the proposed method is very efficient in identifying the diverse types of vessels. Proposed method is also efficient in extracting the abnormal and the thin blood vessels in pathological retinal images. The average values of true positive rate, false positive rate and accuracy offered by the method is 76.32%, 1.99% and 96.28%, respectively for the DRIVE database and 72.82%, 2.6% and 96.16%, respectively for the STARE database. Simulation results demonstrate that the proposed method outperforms the existing methods in detecting the various types of vessels and the neovascularization structures. The combination of curvelet transform and tunable bandpass

  20. Angiotensin II type 1 and 2 receptors and lymphatic vessels modulate lung remodeling and fibrosis in systemic sclerosis and idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Parra, Edwin Roger; Ruppert, Aline Domingos Pinto; Capelozzi, Vera Luiza

    2014-01-01

    To validate the importance of the angiotensin II receptor isotypes and the lymphatic vessels in systemic sclerosis and idiopathic pulmonary fibrosis. We examined angiotensin II type 1 and 2 receptors and lymphatic vessels in the pulmonary tissues obtained from open lung biopsies of 30 patients with systemic sclerosis and 28 patients with idiopathic pulmonary fibrosis. Their histologic patterns included cellular and fibrotic non-specific interstitial pneumonia for systemic sclerosis and usual interstitial pneumonia for idiopathic pulmonary fibrosis. We used immunohistochemistry and histomorphometry to evaluate the number of cells in the alveolar septae and the vessels stained by these markers. Survival curves were also used. We found a significantly increased percentage of septal and vessel cells immunostained for the angiotensin type 1 and 2 receptors in the systemic sclerosis and idiopathic pulmonary fibrosis patients compared with the controls. A similar percentage of angiotensin 2 receptor positive vessel cells was observed in fibrotic non-specific interstitial pneumonia and usual interstitial pneumonia. A significantly increased percentage of lymphatic vessels was present in the usual interstitial pneumonia group compared with the non-specific interstitial pneumonia and control groups. A Cox regression analysis showed a high risk of death for the patients with usual interstitial pneumonia and a high percentage of vessel cells immunostained for the angiotensin 2 receptor in the lymphatic vessels. We concluded that angiotensin II receptor expression in the lung parenchyma can potentially control organ remodeling and fibrosis, which suggests that strategies aimed at preventing high angiotensin 2 receptor expression may be used as potential therapeutic target in patients with pulmonary systemic sclerosis and idiopathic pulmonary fibrosis.

  1. Blood vessel growth blocker may treat AIDS-related Kaposi’s sarcoma

    Science.gov (United States)

    Patients with an AIDS-associated cancer, Kaposi's sarcoma (KS), showed improvement after receiving the combination of bevacizumab, a cancer drug that blocks the growth of new blood vessels, and highly active antiretroviral therapy (HAART).

  2. Fine structural alterations of the blood vessels in the delayed radionecrosis of the human brain and its pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Matsumura, H [Nagasaki Univ. (Japan). School of Medicine

    1981-05-01

    The blood vessels in the delayed radionecrosis of the human brain were studied under light and electron microscopes. Microscopically, the blood vessels demonstrated characteristic findings such as fibrinoid necrosis, hyalinized thickened vessels, perivascular fibrosis and thrombosed vessels. Electron microscopy revealed the formation of fenestrae, separation of endothelial cells, increased pinocytotic vesicles as well as the initial thrombus formation. Our results strongly verified that vascular alterations are primary in the pathogenesis of radionecrosis whereas the parenchymal changes are secondary.

  3. Aminopeptidase A is a functional target in angiogenic blood vessels.

    NARCIS (Netherlands)

    Marchio, S.; Lahdenranta, J.; Schlingemann, R.O.; Valdembri, D.; Wesseling, P.; Arap, M.A.; Hajitou, A.; Ozawa, M.G.; Trepel, M.; Giordano, R.J.; Nanus, D.M.; Dijkman, H.B.P.M.; Oosterwijk, E.; Sidman, R.L.; Cooper, M.D.; Bussolino, F.; Pasqualini, R.; Arap, W.

    2004-01-01

    We show that a membrane-associated protease, aminopeptidase A (APA), is upregulated and enzymatically active in blood vessels of human tumors. To gain mechanistic insight, we evaluated angiogenesis in APA null mice. We found that, although these mice develop normally, they fail to mount the expected

  4. Aminopeptidase A is a functional target in angiogenic blood vessels

    NARCIS (Netherlands)

    Marchiò, Serena; Lahdenranta, Johanna; Schlingemann, Reinier O.; Valdembri, Donatella; Wesseling, Pieter; Arap, Marco A.; Hajitou, Amin; Ozawa, Michael G.; Trepel, Martin; Giordano, Ricardo J.; Nanus, David M.; Dijkman, Henri B. P. M.; Oosterwijk, Egbert; Sidman, Richard L.; Cooper, Max D.; Bussolino, Federico; Pasqualini, Renata; Arap, Wadih

    2004-01-01

    We show that a membrane-associated protease, aminopeptidase A (APA), is upregulated and enzymatically active in blood vessels of human tumors. To gain mechanistic insight, we evaluated angiogenesis in APA null mice. We found that, although these mice develop normally, they fail to mount the expected

  5. Hypoxia-induced pulmonary vascular remodeling requires recruitment of circulating mesenchymal precursors of a monocyte/macrophage lineage.

    Science.gov (United States)

    Frid, Maria G; Brunetti, Jacqueline A; Burke, Danielle L; Carpenter, Todd C; Davie, Neil J; Reeves, John T; Roedersheimer, Mark T; van Rooijen, Nico; Stenmark, Kurt R

    2006-02-01

    Vascular remodeling in chronic hypoxic pulmonary hypertension includes marked fibroproliferative changes in the pulmonary artery (PA) adventitia. Although resident PA fibroblasts have long been considered the primary contributors to these processes, we tested the hypothesis that hypoxia-induced pulmonary vascular remodeling requires recruitment of circulating mesenchymal precursors of a monocyte/macrophage lineage, termed fibrocytes. Using two neonatal animal models (rats and calves) of chronic hypoxic pulmonary hypertension, we demonstrated a dramatic perivascular accumulation of mononuclear cells of a monocyte/macrophage lineage (expressing CD45, CD11b, CD14, CD68, ED1, ED2). Many of these cells produced type I collagen, expressed alpha-smooth muscle actin, and proliferated, thus exhibiting mesenchymal cell characteristics attributed to fibrocytes. The blood-borne origin of these cells was confirmed in experiments wherein circulating monocytes/macrophages of chronically hypoxic rats were in vivo-labeled with DiI fluorochrome via liposome delivery and subsequently identified in the remodeled pulmonary, but not systemic, arterial adventitia. The DiI-labeled cells that appeared in the vessel wall expressed monocyte/macrophage markers and procollagen. Selective depletion of this monocytic cell population, using either clodronate-liposomes or gadolinium chloride, prevented pulmonary adventitial remodeling (ie, production of collagen, fibronectin, and tenascin-C and accumulation of myofibroblasts). We conclude that circulating mesenchymal precursors of a monocyte/macrophage lineage, including fibrocytes, are essential contributors to hypoxia-induced pulmonary vascular remodeling.

  6. Dependence of light scattering profile in tissue on blood vessel diameter and distribution: a computer simulation study.

    Science.gov (United States)

    Duadi, Hamootal; Fixler, Dror; Popovtzer, Rachela

    2013-11-01

    Most methods for measuring light-tissue interactions focus on the volume reflectance while very few measure the transmission. We investigate both diffusion reflection and diffuse transmission at all exit angles to receive the full scattering profile. We also investigate the influence of blood vessel diameter on the scattering profile of a circular tissue. The photon propagation path at a wavelength of 850 nm is calculated from the absorption and scattering constants via Monte Carlo simulation. Several simulations are performed where a different vessel diameter and location were chosen but the blood volume was kept constant. The fraction of photons exiting the tissue at several central angles is presented for each vessel diameter. The main result is that there is a central angle that below which the photon transmission decreased for lower vessel diameters while above this angle the opposite occurred. We find this central angle to be 135 deg for a two-dimensional 10-mm diameter circular tissue cross-section containing blood vessels. These findings can be useful for monitoring blood perfusion and oxygen delivery in the ear lobe and pinched tissues. © 2013 Society of Photo-Optical Instrumentation Engineers (SPIE)

  7. Ultrasonographic Examination of Some Vessels in Dogs and the Characteristics of Blood Flow in These Vessels

    Directory of Open Access Journals (Sweden)

    Figurová M.

    2017-12-01

    Full Text Available The examination by Doppler ultrasonography provides haemodynamic information about blood flow velocity in a respective vessel. It specifies high- and lowresistance flow patterns. The aim of our study was to record the flow in a. carotis communis, a. femoralis and aa. renales in 16 adult clinically healthy dogs of small and medium size; characterize the types of vessels and also determine the pulsatility index (PI and the resistive index (RI of these vessels. The a. femoralis is a high-resistance vessel with a pronounced three-peak waveform. The aa. renales gives a typical picture of a low-resistance flow pattern. The characteristics of a. carotis communis involves different images of its branches a. carotis interna and a. carotis externa. In the investigated groups we observed a medium degree of pulsatility (atypical highresistance flow pattern with an absence of reverse flow. The mean measured values of indices for a. carotis communis were: left side PI 1.824 and RI 0.742; right side PI 1.891 and RI 0.746, and for aa. renales: PI 1.366 ± 0.04 and RI 0.684 ± 0.05.

  8. Vascular patterns in the heads of crocodilians: blood vessels and sites of thermal exchange.

    Science.gov (United States)

    Porter, William Ruger; Sedlmayr, Jayc C; Witmer, Lawrence M

    2016-12-01

    Extant crocodilians are a highly apomorphic archosaur clade that is ectothermic, yet often achieve large body sizes that can be subject to higher heat loads. Therefore, the anatomical and physiological roles that blood vessels play in crocodilian thermoregulation need further investigation to better understand how crocodilians establish and maintain cephalic temperatures and regulate neurosensory tissue temperatures during basking and normal activities. The cephalic vascular anatomy of extant crocodilians, particularly American alligator (Alligator mississippiensis) was investigated using a differential-contrast, dual-vascular injection technique and high resolution X-ray micro-computed tomography (μCT). Blood vessels were digitally isolated to create representations of vascular pathways. The specimens were then dissected to confirm CT results. Sites of thermal exchange, consisting of the oral, nasal, and orbital regions, were given special attention due to their role in evaporative cooling and cephalic thermoregulation in other diapsids. Blood vessels to and from sites of thermal exchange were studied to detect conserved vascular patterns and to assess their ability to deliver cooled blood to neurosensory tissues. Within the orbital region, both the arteries and veins demonstrated consistent branching patterns, with the supraorbital, infraorbital, and ophthalmotemporal vessels supplying and draining the orbit. The venous drainage of the orbital region showed connections to the dural sinuses via the orbital veins and cavernous sinus. The palatal region demonstrated a vast plexus that comprised both arteries and veins. The most direct route of venous drainage of the palatal plexus was through the palatomaxillary veins, essentially bypassing neurosensory tissues. Anastomotic connections with the nasal region, however, may provide an alternative route for palatal venous blood to reach neurosensory tissues. The nasal region in crocodilians is probably the most

  9. Hybrid PIV-PTV technique for measuring blood flow in rat mesenteric vessels.

    Science.gov (United States)

    Ha, Hojin; Nam, Kweon-Ho; Lee, Sang Joon

    2012-11-01

    The micro-particle tracking velocimetry (μ-PTV) technique is used to obtain the velocity fields of blood flow in the microvasculature under in vivo conditions because it can provide the blood velocity distribution in microvessels with high spatial resolution. The in vivo μ-PTV technique usually requires a few to tens of seconds to obtain a whole velocity profile across the vessel diameter because of the limited number density of tracer particles under in vivo conditions. Thus, the μ-PTV technique alone is limited in measuring unsteady blood flows that fluctuate irregularly due to the heart beating and muscle movement in surrounding tissues. In this study, a new hybrid PIV-PTV technique was established by combining PTV and particle image velocimetry (PIV) techniques to resolve the drawbacks of the μ-PTV method in measuring blood flow in microvessels under in vivo conditions. Images of red blood cells (RBCs) and fluorescent particles in rat mesenteric vessels were obtained simultaneously. Temporal variations of the centerline blood velocity were monitored using a fast Fourier transform-based cross-correlation PIV method. The fluorescence particle images were analyzed using the μ-PTV technique to extract the spatial distribution of the velocity vectors. Data from the μ-PTV and PIV methods were combined to obtain a better estimate of the velocity profile in actual blood flow. This technique will be useful in investigating hemodynamics in microcirculation by measuring unsteady irregular blood flows more accurately. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Feasibility evaluation of 3D photoacoustic imaging of blood vessel structure using multiple wavelengths with a handheld probe

    Science.gov (United States)

    Uchimoto, Yo; Namita, Takeshi; Kondo, Kengo; Yamakawa, Makoto; Shiina, Tsuyoshi

    2018-02-01

    Photoacoustic imaging is anticipated for use in portraying blood vessel structures (e.g. neovascularization in inflamed regions). To reduce invasiveness and enhance ease handling, we developed a handheld photoacoustic imaging system using multiple wavelengths. The usefulness of the proposed system was investigated in phantom experiments and in vivo measurements. A silicon tube was embedded into chicken breast meat to simulate the blood vessel. The tube was filled with ovine blood. Then laser light was guided to the phantom surface by an optical fiber bundle close to the linear ultrasound probe. Photoacoustic images were obtained at 750-950 nm wavelengths. Strong photoacoustic signals from the boundary between blood and silicon tube are observed in these images. The shape of photoacoustic spectrum at the boundary resembles that of the HbO2 absorption spectrum at 750-920 nm. In photoacoustic images, similarity between photoacoustic spectrum and HbO2 absorption spectrum was evaluated by calculating the normalized correlation coefficient. Results show high correlation in regions of strong photoacoustic signals in photoacoustic images. These analyses demonstrate the feasibility of portraying blood vessel structures under practical conditions. To evaluate the feasibility of three-dimensional vascular imaging, in vivo experiments were conducted using three wavelengths. A right hand and ultrasound probe were set in degassed water. By scanning a probe, cross-sectional ultrasound and photoacoustic images were obtained at each location. Then, all ultrasound or photoacoustic images were piled up respectively. Then three-dimensional images were constructed. Resultant images portrayed blood vessel-like structures three-dimensionally. Furthermore, to distinguish blood vessels from other tissues (e.g. skin), distinguishing images of them were constructed by comparing photoacoustic signal intensity among three wavelengths. The resultant image portrayed blood vessels as

  11. Analysis of trends and prospects regarding stents for human blood vessels.

    Science.gov (United States)

    Lee, Jeong Hee; Kim, Eung Do; Jun, Eun Jung; Yoo, Hyoung Sun; Lee, Joon Woo

    2018-01-01

    The purpose of this paper is to provide technology trends and information regarding market and prospects in stents used for human blood vessels in Korea and the world.A stent is a medical device in the form of a cylindrical metal net used to normalize flow when blood or other bodily fluids such as biliary fluids are obstructed in blood vessels, gastrointestinal tracts, etc. by inserting the stent into a narrowed or clogged area. Stents are classified into vascular and non-vascular stents. The coronary artery stent is avascular stent that is used for coronary atherosclerosis.The demand is increasing for stents to treat diseases such as those affecting the heart and blood vessels of elderly and middle-aged patients. Due to the current shift in the demographic structure caused by an aging society, the prospect for stents seems to be very bright.The use of a stent designed to prevent acute vascular occlusion and restenosis, which is a side effect of conventional balloon angioplasty, has rapidly become popular because it can prevent acute complications and improve clinical outcomes. Since the initial release of this stent, there have been significant developments in its design, the most notable of which has been the introduction of drug-eluting stents (DES). Bioresorbable scaffolds (BRS) have the potential to introduce a paradigm shift in interventional cardiology, a true anatomical and functional "vascular restoration" instead of an artificial stiff tube encased by a persistent metallic foreign body. Data for this research were gathered from primary and secondary sources as well as the databases of the Korea Institute of Science Technology Information (KISTI) located in Seoul, Korea like KISTI Market Report. The sources used for primary research included the databases available from the Korea Institute of Science Technology Information, past industry research services/studies, economic and demographic data, and trade and industry journals. Secondary research was used

  12. An experimental system for the study of ultrasound exposure of isolated blood vessels

    International Nuclear Information System (INIS)

    Tokarczyk, Anna; Rivens, Ian; Symonds-Tayler, Richard; Ter Haar, Gail; Van Bavel, E

    2013-01-01

    An experimental system designed for the study of the effects of diagnostic or therapeutic ultrasound exposure on isolated blood vessels in the presence or absence of intraluminal contrast agent is described. The system comprised several components. A microscope was used to monitor vessel size (and thus vessel functionality), and potential leakage of intraluminal 70 kDa FITC-dextran fluorescence marker. A vessel chamber allowed the mounting of an isolated vessel whilst maintaining its viability, with pressure regulation for the control of intraluminal pressure and induction of flow for the infusion of contrast microbubbles. A fibre-optic hydrophone sensor mounted on the vessel chamber using a micromanipulator allowed pre-exposure targeting of the vessel to within 150 µm, and monitoring of acoustic cavitation emissions during exposures. Acoustic cavitation was also detected using changes in the ultrasound drive voltage and by detection of audible emissions using a submerged microphone. The suitability of this system for studying effects in the isolated vessel model has been demonstrated using a pilot study of 6 sham exposed and 18 high intensity focused ultrasound exposed vessels, with or without intraluminal contrast agent (SonoVue) within the vessels. (paper)

  13. Angiogenesis and blood vessel stability in inflammatory arthritis.

    LENUS (Irish Health Repository)

    Kennedy, Aisling

    2012-02-01

    OBJECTIVE: To assess blood vessel stability in inflammatory synovial tissue (ST) and to examine neural cell adhesion molecule (NCAM), oxidative DNA damage, and hypoxia in vivo. METHODS: Macroscopic vascularity and ST oxygen levels were determined in vivo in patients with inflammatory arthritis who were undergoing arthroscopy. Vessel maturity\\/stability was quantified in matched ST samples by dual immunofluorescence staining for factor VIII (FVIII)\\/alpha-smooth muscle actin (alpha-SMA). NCAM and 8-oxo-7,8-dihydro-2\\'-deoxyguanosine (8-oxodG) were examined by immunohistochemistry. Angiogenesis was assessed in vitro, using human dermal endothelial cells (HDECs) in a Matrigel tube formation assay. RESULTS: A significant number of immature vessels (showing no pericyte recruitment) was observed in tissue from patients with inflammatory arthritis (P < 0.001), in contrast to osteoarthritic and normal tissue, which showed complete recruitment of pericytes. Low in vivo PO(2) levels in the inflamed joint (median [range] 22.8 [3.2-54.1] mm Hg) were inversely related to increased macroscopic vascularity (P < 0.04) and increased microscopic expression of FVIII and alpha-SMA (P < 0.04 and P < 0.03, respectively). A significant proportion of vessels showed focal expression of NCAM and strong nuclear 8-oxodG expression, implicating a loss of EC-pericyte contact and increased DNA damage, levels of which were inversely associated with low in vivo PO(2) (P = 0.04 for each comparison). Circulating cells were completely negative for 8-oxodG. Exposure of HDEC to 3% O(2) (reflecting mean ST in vivo measurements) significantly increased EC tube formation (P < 0.05). CONCLUSION: Our findings indicate the presence of unstable vessels in inflamed joints associated with hypoxia, incomplete EC-pericyte interactions, and increased DNA damage. These changes may further contribute to persistent hypoxia in the inflamed joint to further drive this unstable microenvironment.

  14. Why are tumour blood vessels abnormal and why is it important to know?

    Science.gov (United States)

    Nagy, J A; Chang, S-H; Dvorak, A M; Dvorak, H F

    2009-01-01

    Tumour blood vessels differ from their normal counterparts for reasons that have received little attention. We report here that they are of at least six distinct types, we describe how each forms, and, looking forward, encourage the targeting of tumour vessel subsets that have lost their vascular endothelial growth factor-A (VEGF-A) dependency and so are likely unresponsive to anti-VEGF-A therapies. PMID:19240721

  15. Endothelial Mineralocorticoid Receptor Mediates Parenchymal Arteriole and Posterior Cerebral Artery Remodeling During Angiotensin II-Induced Hypertension.

    Science.gov (United States)

    Diaz-Otero, Janice M; Fisher, Courtney; Downs, Kelsey; Moss, M Elizabeth; Jaffe, Iris Z; Jackson, William F; Dorrance, Anne M

    2017-12-01

    The brain is highly susceptible to injury caused by hypertension because the increased blood pressure causes artery remodeling that can limit cerebral perfusion. Mineralocorticoid receptor (MR) antagonism prevents hypertensive cerebral artery remodeling, but the vascular cell types involved have not been defined. In the periphery, the endothelial MR mediates hypertension-induced vascular injury, but cerebral and peripheral arteries are anatomically distinct; thus, these findings cannot be extrapolated to the brain. The parenchymal arterioles determine cerebrovascular resistance. Determining the effects of hypertension and MR signaling on these arterioles could lead to a better understanding of cerebral small vessel disease. We hypothesized that endothelial MR signaling mediates inward cerebral artery remodeling and reduced cerebral perfusion during angiotensin II (AngII) hypertension. The biomechanics of the parenchymal arterioles and posterior cerebral arteries were studied in male C57Bl/6 and endothelial cell-specific MR knockout mice and their appropriate controls using pressure myography. AngII increased plasma aldosterone and decreased cerebral perfusion in C57Bl/6 and MR-intact littermates. Endothelial cell MR deletion improved cerebral perfusion in AngII-treated mice. AngII hypertension resulted in inward hypotrophic remodeling; this was prevented by MR antagonism and endothelial MR deletion. Our studies suggest that endothelial cell MR mediates hypertensive remodeling in the cerebral microcirculation and large pial arteries. AngII-induced inward remodeling of cerebral arteries and arterioles was associated with a reduction in cerebral perfusion that could worsen the outcome of stroke or contribute to vascular dementia. © 2017 American Heart Association, Inc.

  16. Tight junction between endothelial cells: the interaction between nanoparticles and blood vessels

    Directory of Open Access Journals (Sweden)

    Yue Zhang

    2016-05-01

    Full Text Available Since nanoparticles are now widely applied as food additives, in cosmetics and other industries, especially in medical therapy and diagnosis, we ask here whether nanoparticles can cause several adverse effects to human health. In this review, based on research on nanotoxicity, we mainly discuss the negative influence of nanoparticles on blood vessels in several aspects and the potential mechanism for nanoparticles to penetrate endothelial layers of blood vessels, which are the sites of phosphorylation of tight junction proteins (claudins, occludins, and ZO (Zonula occludens proteins, oxidative stress and shear stress. We propose a connection between the presence of nanoparticles and the regulation of the tight junction, which might be the key approach for nanoparticles to penetrate endothelial layers and then have an impact on other tissues and organs.

  17. Multi-detector spiral CT study of the relationships between pulmonary ground-glass nodules and blood vessels

    International Nuclear Information System (INIS)

    Gao, Feng; Li, Ming; Ge, Xiaojun; Ren, Qingguo; Hua, Yanqing; Zheng, Xiangpeng; Chen, Yan; Lv, Fangzhen

    2013-01-01

    To investigate the relationships between pulmonary ground-glass nodules (GGN) and blood vessels and their diagnostic values in differentiating GGNs. Multi-detector spiral CT imaging of 108 GGNs was retrospectively reviewed. The spatial relationships between GGNs and supplying blood vessels were categorized into four types: I, vessels passing by GGNs; II, intact vessels passing through GGNs; III, distorted, dilated or tortuous vessels seen within GGNs; IV, more complicated vasculature other than described above. Relationship types were correlated to pathologic and/or clinical findings of GGNs. Of 108 GGNs, 10 were benign, 24 preinvasive nodules and 74 adenocarcinomas that were pathologically proven. Types I, II, III and IV vascular relationships were observed in 9, 58, 21 and 20 GGNs, respectively. Type II relationship was the dominating relationship for each GGN group, but significant differences were shown among them. Correlation analysis showed strong correlation between invasive adenocarcinoma and type III and IV relationships. Subgroup analysis indicated that type III was more commonly seen in IAC with comparison to type IV more likely seen in MIA. Different GGNs have different relationships with vessels. Understanding and recognising characteristic GGN-vessel relationships may help identify which GGNs are more likely to be malignant. (orig.)

  18. Neutrophil-Mediated Delivery of Therapeutic Nanoparticles across Blood Vessel Barrier for Treatment of Inflammation and Infection

    OpenAIRE

    Chu, Dafeng; Gao, Jin; Wang, Zhenjia

    2015-01-01

    Endothelial cells form a monolayer in lumen of blood vessels presenting a great barrier for delivery of therapeutic nanoparticles (NPs) into extravascular tissues where most diseases occur, such as inflammation disorders and infection. Here, we report a strategy for delivering therapeutic NPs across this blood vessel barrier by nanoparticle in situ hitchhiking activated neutrophils. Using intravital microscopy of TNF-α-induced inflammation of mouse cremaster venules and a mouse model of acute...

  19. In vivo measurement of hemodynamic information in stenosed rat blood vessels using X-ray PIV.

    Science.gov (United States)

    Park, Hanwook; Park, Jun Hong; Lee, Sang Joon

    2016-11-28

    Measurements of the hemodynamic information of blood flows, especially wall shear stress (WSS), in animal models with circulatory vascular diseases (CVDs) are important to understand the pathological mechanism of CVDs. In this study, X-ray particle image velocimetry (PIV) with high spatial resolution was applied to obtain velocity field information in stenosed blood vessels with high WSS. 3D clips fabricated with a 3D printer were applied to the abdominal aorta of a rat cadaver to induce artificial stenosis in the real blood vessel of an animal model. The velocity and WSS information of blood flows in the stenosed vessel were obtained and compared at various stenosis severities. In vivo measurement was also conducted by fastening a stenotic clip on a live rat model through surgical intervention to reduce the flow rate to match the limited temporal resolution of the present X-ray PIV system. Further improvement of the temporal resolution of the system might be able to provide in vivo measurements of hemodynamic information from animal disease models under physiological conditions. The present results would be helpful for understanding the relation between hemodynamic characteristics and the pathological mechanism in animal CVD models.

  20. Delayed astrocytic contact with cerebral blood vessels in FGF-2 deficient mice does not compromise permeability properties at the developing blood-brain barrier.

    Science.gov (United States)

    Saunders, Norman R; Dziegielewska, Katarzyna M; Unsicker, Klaus; Ek, C Joakim

    2016-11-01

    The brain functions within a specialized environment tightly controlled by brain barrier mechanisms. Understanding the regulation of barrier formation is important for understanding brain development and may also lead to finding new ways to deliver pharmacotherapies to the brain; access of many potentially promising drugs is severely hindered by these barrier mechanisms. The cellular composition of the neurovascular unit of the blood-brain barrier proper and their effects on regulation of its function are beginning to be understood. One hallmark of the neurovascular unit in the adult is the astroglial foot processes that tightly surround cerebral blood vessels. However their role in barrier formation is still unclear. In this study we examined barrier function in newborn, juvenile and adult mice lacking fibroblast growth factor-2 (FGF-2), which has been shown to result in altered astroglial differentiation during development. We show that during development of FGF-2 deficient mice the astroglial contacts with cerebral blood vessels are delayed compared with wild-type animals. However, this delay did not result in changes to the permeability properties of the blood brain barrier as assessed by exclusion of either small or larger sized molecules at this interface. In addition cerebral vessels were positive for tight-junction proteins and we observed no difference in the ultrastructure of the tight-junctions. The results indicate that the direct contact of astroglia processes to cerebral blood vessels is not necessary for either the formation of the tight-junctions or for basic permeability properties and function of the blood-brain barrier. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1201-1212, 2016. © 2016 Wiley Periodicals, Inc.

  1. Vascular Patterns in Iguanas and Other Squamates: Blood Vessels and Sites of Thermal Exchange.

    Directory of Open Access Journals (Sweden)

    William Ruger Porter

    Full Text Available Squamates use the circulatory system to regulate body and head temperatures during both heating and cooling. The flexibility of this system, which possibly exceeds that of endotherms, offers a number of physiological mechanisms to gain or retain heat (e.g., increase peripheral blood flow and heart rate, cooling the head to prolong basking time for the body as well as to shed heat (modulate peripheral blood flow, expose sites of thermal exchange. Squamates also have the ability to establish and maintain the same head-to-body temperature differential that birds, crocodilians, and mammals demonstrate, but without a discrete rete or other vascular physiological device. Squamates offer important anatomical and phylogenetic evidence for the inference of the blood vessels of dinosaurs and other extinct archosaurs in that they shed light on the basal diapsid condition. Given this basal positioning, squamates likewise inform and constrain the range of physiological thermoregulatory mechanisms that may have been found in Dinosauria. Unfortunately, the literature on squamate vascular anatomy is limited. Cephalic vascular anatomy of green iguanas (Iguana iguana was investigated using a differential-contrast, dual-vascular injection (DCDVI technique and high-resolution X-ray microcomputed tomography (μCT. Blood vessels were digitally segmented to create a surface representation of vascular pathways. Known sites of thermal exchange, consisting of the oral, nasal, and orbital regions, were given special attention due to their role in brain and cephalic thermoregulation. Blood vessels to and from sites of thermal exchange were investigated to detect conserved vascular patterns and to assess their ability to deliver cooled blood to the dural venous sinuses. Arteries within sites of thermal exchange were found to deliver blood directly and through collateral pathways. The venous drainage was found to have multiple pathways that could influence neurosensory

  2. Vascular Patterns in Iguanas and Other Squamates: Blood Vessels and Sites of Thermal Exchange.

    Science.gov (United States)

    Porter, William Ruger; Witmer, Lawrence M

    2015-01-01

    Squamates use the circulatory system to regulate body and head temperatures during both heating and cooling. The flexibility of this system, which possibly exceeds that of endotherms, offers a number of physiological mechanisms to gain or retain heat (e.g., increase peripheral blood flow and heart rate, cooling the head to prolong basking time for the body) as well as to shed heat (modulate peripheral blood flow, expose sites of thermal exchange). Squamates also have the ability to establish and maintain the same head-to-body temperature differential that birds, crocodilians, and mammals demonstrate, but without a discrete rete or other vascular physiological device. Squamates offer important anatomical and phylogenetic evidence for the inference of the blood vessels of dinosaurs and other extinct archosaurs in that they shed light on the basal diapsid condition. Given this basal positioning, squamates likewise inform and constrain the range of physiological thermoregulatory mechanisms that may have been found in Dinosauria. Unfortunately, the literature on squamate vascular anatomy is limited. Cephalic vascular anatomy of green iguanas (Iguana iguana) was investigated using a differential-contrast, dual-vascular injection (DCDVI) technique and high-resolution X-ray microcomputed tomography (μCT). Blood vessels were digitally segmented to create a surface representation of vascular pathways. Known sites of thermal exchange, consisting of the oral, nasal, and orbital regions, were given special attention due to their role in brain and cephalic thermoregulation. Blood vessels to and from sites of thermal exchange were investigated to detect conserved vascular patterns and to assess their ability to deliver cooled blood to the dural venous sinuses. Arteries within sites of thermal exchange were found to deliver blood directly and through collateral pathways. The venous drainage was found to have multiple pathways that could influence neurosensory tissue temperature

  3. Regulation of cellular communication by signaling microdomains in the blood vessel wall.

    Science.gov (United States)

    Billaud, Marie; Lohman, Alexander W; Johnstone, Scott R; Biwer, Lauren A; Mutchler, Stephanie; Isakson, Brant E

    2014-01-01

    It has become increasingly clear that the accumulation of proteins in specific regions of the plasma membrane can facilitate cellular communication. These regions, termed signaling microdomains, are found throughout the blood vessel wall where cellular communication, both within and between cell types, must be tightly regulated to maintain proper vascular function. We will define a cellular signaling microdomain and apply this definition to the plethora of means by which cellular communication has been hypothesized to occur in the blood vessel wall. To that end, we make a case for three broad areas of cellular communication where signaling microdomains could play an important role: 1) paracrine release of free radicals and gaseous molecules such as nitric oxide and reactive oxygen species; 2) role of ion channels including gap junctions and potassium channels, especially those associated with the endothelium-derived hyperpolarization mediated signaling, and lastly, 3) mechanism of exocytosis that has considerable oversight by signaling microdomains, especially those associated with the release of von Willebrand factor. When summed, we believe that it is clear that the organization and regulation of signaling microdomains is an essential component to vessel wall function.

  4. Adaptable three-dimensional Monte Carlo modeling of imaged blood vessels in skin

    Science.gov (United States)

    Pfefer, T. Joshua; Barton, Jennifer K.; Chan, Eric K.; Ducros, Mathieu G.; Sorg, Brian S.; Milner, Thomas E.; Nelson, J. Stuart; Welch, Ashley J.

    1997-06-01

    In order to reach a higher level of accuracy in simulation of port wine stain treatment, we propose to discard the typical layered geometry and cylindrical blood vessel assumptions made in optical models and use imaging techniques to define actual tissue geometry. Two main additions to the typical 3D, weighted photon, variable step size Monte Carlo routine were necessary to achieve this goal. First, optical low coherence reflectometry (OLCR) images of rat skin were used to specify a 3D material array, with each entry assigned a label to represent the type of tissue in that particular voxel. Second, the Monte Carlo algorithm was altered so that when a photon crosses into a new voxel, the remaining path length is recalculated using the new optical properties, as specified by the material array. The model has shown good agreement with data from the literature. Monte Carlo simulations using OLCR images of asymmetrically curved blood vessels show various effects such as shading, scattering-induced peaks at vessel surfaces, and directionality-induced gradients in energy deposition. In conclusion, this augmentation of the Monte Carlo method can accurately simulate light transport for a wide variety of nonhomogeneous tissue geometries.

  5. Regulation of Cellular Communication by Signaling Microdomains in the Blood Vessel Wall

    Science.gov (United States)

    Billaud, Marie; Lohman, Alexander W.; Johnstone, Scott R.; Biwer, Lauren A.; Mutchler, Stephanie; Isakson, Brant E.

    2014-01-01

    It has become increasingly clear that the accumulation of proteins in specific regions of the plasma membrane can facilitate cellular communication. These regions, termed signaling microdomains, are found throughout the blood vessel wall where cellular communication, both within and between cell types, must be tightly regulated to maintain proper vascular function. We will define a cellular signaling microdomain and apply this definition to the plethora of means by which cellular communication has been hypothesized to occur in the blood vessel wall. To that end, we make a case for three broad areas of cellular communication where signaling microdomains could play an important role: 1) paracrine release of free radicals and gaseous molecules such as nitric oxide and reactive oxygen species; 2) role of ion channels including gap junctions and potassium channels, especially those associated with the endothelium-derived hyperpolarization mediated signaling, and lastly, 3) mechanism of exocytosis that has considerable oversight by signaling microdomains, especially those associated with the release of von Willebrand factor. When summed, we believe that it is clear that the organization and regulation of signaling microdomains is an essential component to vessel wall function. PMID:24671377

  6. Magnetic navigation system for the precise helical and translational motions of a microrobot in human blood vessels

    Science.gov (United States)

    Jeon, S. M.; Jang, G. H.; Choi, H. C.; Park, S. H.; Park, J. O.

    2012-04-01

    Different magnetic navigation systems (MNSs) have been investigated for the wireless manipulation of microrobots in human blood vessels. Here we propose a MNS and methodology for generation of both the precise helical and translational motions of a microrobot to improve its maneuverability in complex human blood vessel. We then present experiments demonstrating the helical and translational motions of a spiral-type microrobot to verify the proposed MNS.

  7. The effect of transluminal stent-graft placement on blood flow of abdominal branch vessels in type B aortic dissection

    International Nuclear Information System (INIS)

    Huang Lianjun; Yang Jian; Yu Feicheng; Sun Lizhong; Zhu Junming; Zhang Yan; Jiang Shiliang

    2005-01-01

    Objective: To evaluate the effect of TSGP on blood flow of abdominal branch vessels of Type B dissection. Methods: Thirty-five patients with type B aortic dissection underwent TSGP. The blood flow of abdominal branch vessels was analyzed via EBCT, MRI, and DSA before and after procedure. Results: A total of 140 important vessels from abdominal aorta in 35 patients, including celiac artery, SMA, right and left renal arteries were analyzed via EBCT, MRI, and DSA. 58 branches were affected by dissection, of which 14 (10% ) were dynamic impairment; and 44 (31.4%) were static impairment. After TSGP, the blood flow of impaired branches all showed improvement at different degrees, no post-operative ischemic complications occurred. Conclusion: TSGP could improve the blood flow immediately not only the dynamic but also the static ischemia of abdominal aorta branch vessels caused by type B aortic dissection. Further study is still need to observe the mid-term and long-term effect of TSGP. (authors)

  8. [Conjunct changes in the resistance and engorgement of the cerebral vessels in shifts in the blood gas composition].

    Science.gov (United States)

    Krasil'nikov, V G; Artem'eva, A I

    1982-08-01

    In anesthetized cats, under perfusion and with constant volume of the hemodynamically isolated brain, hypercapnia and hypoxia led to a decrease of cerebral vessels resistance and to a reduction of the brain blood flow, whereas a decrease in the PCO2 and an increase in the PO2 in the blood exerted on opposite effect. The different responses of the vessels had some similar features in respect to threshold changes of the PCO2 and PO2, to potentiation of effects of both parts of the brain vascular system on increased shifts of the blood gas tension, to greater sensitivity of both parts to PCO2 changes, to effect of the blood gas tension on reactivity of both parts to noradrenaline. The authors suggest a possibility of alterations of the filter-absorption interrelationships in the brain due to different responses of arterial and venous vessels to changes of the blood gas tension.

  9. Extraction of liver volumetry based on blood vessel from the portal phase CT dataset

    Science.gov (United States)

    Maklad, Ahmed S.; Matsuhiro, Mikio; Suzuki, Hidenobu; Kawata, Yoshiki; Niki, Noboru; Utsunomiya, Tohru; Shimada, Mitsuo

    2012-02-01

    At liver surgery planning stage, the liver volumetry would be essential for surgeons. Main problem at liver extraction is the wide variability of livers in shapes and sizes. Since, hepatic blood vessels structure varies from a person to another and covers liver region, the present method uses that information for extraction of liver in two stages. The first stage is to extract abdominal blood vessels in the form of hepatic and nonhepatic blood vessels. At the second stage, extracted vessels are used to control extraction of liver region automatically. Contrast enhanced CT datasets at only the portal phase of 50 cases is used. Those data include 30 abnormal livers. A reference for all cases is done through a comparison of two experts labeling results and correction of their inter-reader variability. Results of the proposed method agree with the reference at an average rate of 97.8%. Through application of different metrics mentioned at MICCAI workshop for liver segmentation, it is found that: volume overlap error is 4.4%, volume difference is 0.3%, average symmetric distance is 0.7 mm, Root mean square symmetric distance is 0.8 mm, and maximum distance is 15.8 mm. These results represent the average of overall data and show an improved accuracy compared to current liver segmentation methods. It seems to be a promising method for extraction of liver volumetry of various shapes and sizes.

  10. Primo vessel inside a lymph vessel emerging from a cancer tissue.

    Science.gov (United States)

    Lee, Sungwoo; Ryu, Yeonhee; Cha, Jinmyung; Lee, Jin-Kyu; Soh, Kwang-Sup; Kim, Sungchul; Lim, Jaekwan

    2012-10-01

    Primo vessels were observed inside the lymph vessels near the caudal vena cava of a rabbit and a rat and in the thoracic lymph duct of a mouse. In the current work we found a primo vessel inside the lymph vessel that came out from the tumor tissue of a mouse. A cancer model of a nude mouse was made with human lung cancer cell line NCI-H460. We injected fluorescent nanoparticles into the xenografted tumor tissue and studied their flow in blood, lymph, and primo vessels. Fluorescent nanoparticles flowed through the blood vessels quickly in few minutes, and but slowly in the lymph vessels. The bright fluorescent signals of nanoparticles disappeared within one hour in the blood vessels but remained much longer up to several hours in the case of lymph vessels. We found an exceptional case of lymph vessels that remained bright with fluorescence up to 24 hours. After detailed examination we found that the bright fluorescence was due to a putative primo vessel inside the lymph vessel. This rare observation is consistent with Bong-Han Kim's claim on the presence of a primo vascular system in lymph vessels. It provides a significant suggestion on the cancer metastasis through primo vessels and lymph vessels. Copyright © 2012. Published by Elsevier B.V.

  11. [Do double gloves protect against contamination during cannulation of blood vessels? A prospective randomized study].

    Science.gov (United States)

    Szarpak, Łukasz; Kurowski, Andrzej

    2014-01-01

    Undamaged medical gloves protect medical personnel from contact with physiological fluids of the patient. Thus they protect the assistance provider from hand skin contamination with potentially infectious biological materials. The aim of the study was to evaluate the occurrence of pierce, perforations or damage of medical gloves during cannulation of blood vessels. In the prospective randomized study 303 pairs of gloves, used during cannulation of blood vessels under simulated resuscitation, were analyzed. Gloves were tested by the water leak test. The water test revealed 44 cases of damage to the gloves used during cannulation of blood vessels. Significant differences were noted in the frequency of damage to both the outer and single pairs of gloves and the inner pair of gloves. The study showed that the use of double gloves provides a higher level of security for a paramedic than the use of a single pair of gloves, however, double gloves reduce the manual dexterity of a paramedic. A large number of damages to gloves are not noticed by medical personnel during surgery.

  12. The Behaviors of Ferro-Magnetic Nano-Particles In and Around Blood Vessels under Applied Magnetic Fields

    Science.gov (United States)

    Nacev, A.; Beni, C.; Bruno, O.; Shapiro, B.

    2010-01-01

    In magnetic drug delivery, therapeutic magnetizable particles are typically injected into the blood stream and magnets are then used to concentrate them to disease locations. The behavior of such particles in-vivo is complex and is governed by blood convection, diffusion (in blood and in tissue), extravasation, and the applied magnetic fields. Using physical first-principles and a sophisticated vessel-membrane-tissue (VMT) numerical solver, we comprehensively analyze in detail the behavior of magnetic particles in blood vessels and surrounding tissue. For any blood vessel (of any size, depth, and blood velocity) and tissue properties, particle size and applied magnetic fields, we consider a Krogh tissue cylinder geometry and solve for the resulting spatial distribution of particles. We find that there are three prototypical behaviors (blood velocity dominated, magnetic force dominated, and boundary-layer formation) and that the type of behavior observed is uniquely determined by three non-dimensional numbers (the magnetic-Richardson number, mass Péclet number, and Renkin reduced diffusion coefficient). Plots and equations are provided to easily read out which behavior is found under which circumstances (Figures 5, 6, 7, and 8). We compare our results to previously published in-vitro and in-vivo magnetic drug delivery experiments. Not only do we find excellent agreement between our predictions and prior experimental observations, but we are also able to qualitatively and quantitatively explain behavior that was previously not understood. PMID:21278859

  13. Migraine aura pathophysiology: the role of blood vessels and microembolisation

    OpenAIRE

    Dalkara, Turgay; Nozari, Ala; Moskowitz, Michael A

    2010-01-01

    Migraine attacks with auras are sometimes associated with underlying hereditary or acquired cerebrovascular disorders. A unifying pathophysiological explanation linking migraine to these conditions has been diffcult to identify. On the basis of genetic and epidemiological evidence, we suggest that changes in blood vessels, hypoperfusion disorders, and microembolisation can cause neurovascular dysfunction and evoke cortical spreading depression, an event that is widely thought to underlie aura...

  14. A Morphological Hessian Based Approach for Retinal Blood Vessels Segmentation and Denoising Using Region Based Otsu Thresholding.

    Directory of Open Access Journals (Sweden)

    Khan BahadarKhan

    Full Text Available Diabetic Retinopathy (DR harm retinal blood vessels in the eye causing visual deficiency. The appearance and structure of blood vessels in retinal images play an essential part in the diagnoses of an eye sicknesses. We proposed a less computational unsupervised automated technique with promising results for detection of retinal vasculature by using morphological hessian based approach and region based Otsu thresholding. Contrast Limited Adaptive Histogram Equalization (CLAHE and morphological filters have been used for enhancement and to remove low frequency noise or geometrical objects, respectively. The hessian matrix and eigenvalues approach used has been in a modified form at two different scales to extract wide and thin vessel enhanced images separately. Otsu thresholding has been further applied in a novel way to classify vessel and non-vessel pixels from both enhanced images. Finally, postprocessing steps has been used to eliminate the unwanted region/segment, non-vessel pixels, disease abnormalities and noise, to obtain a final segmented image. The proposed technique has been analyzed on the openly accessible DRIVE (Digital Retinal Images for Vessel Extraction and STARE (STructured Analysis of the REtina databases along with the ground truth data that has been precisely marked by the experts.

  15. Von Willebrand factor regulation of blood vessel formation.

    Science.gov (United States)

    Randi, Anna M; Smith, Koval E; Castaman, Giancarlo

    2018-06-04

    Several important physiological processes, from permeability to inflammation to haemostasis, take place at the vessel wall and are regulated by endothelial cells (EC). Thus, proteins that have been identified as regulators of one process are increasingly found to be involved in other vascular functions. Such is the case for Von Willebrand Factor (VWF), a large glycoprotein best known for its critical role in haemostasis. In vitro and in vivo studies have shown that lack of VWF causes enhanced vascularisation, both constitutively and following ischemia. This evidence is supported by studies on blood outgrowth endothelial cells (BOEC) from patients with lack of VWF synthesis (type 3 von Willebrand disease [VWD]). The molecular pathways are likely to involve VWF binding partners, such as integrin αvβ3, and components of Weibel Palade bodies (WPB), such as Angiopoietin-2 and Galectin-3, whose storage is regulated by VWF; these converge on the master regulator of angiogenesis and endothelial homeostasis, vascular endothelial growth factor (VEGF) signalling. Recent studies suggest that the roles of VWF may be tissue-specific. The ability of VWF to regulate angiogenesis has clinical implications for a subset of VWD patients with severe, intractable gastrointestinal bleeding due to vascular malformations. In this article, we review the evidence showing that VWF is involved in blood vessel formation, discuss the role of VWF high molecular weight multimers in regulating angiogenesis, and the value of studies on BOEC in developing a precision medicine approach to validate novel treatments for angiodysplasia in congenital VWD and acquired von Willebrand syndrome. Copyright © 2018 American Society of Hematology.

  16. Fibre optic confocal imaging (FOCI) of keratinocytes, blood vessels and nerves in hairless mouse skin in vivo

    Science.gov (United States)

    BUSSAU, L. J.; VO, L. T.; DELANEY, P. M.; PAPWORTH, G. D.; BARKLA, D. H.; KING, R. G.

    1998-01-01

    Fibre optic confocal imaging (FOCI) enabled subsurface fluorescence microscopy of the skin of hairless mice in vivo. Application of acridine orange enabled imaging of the layers of the epidermis. The corneocytes of the stratum corneum, the keratinocytes in the basal layers and redundant hair follicles were visualised at depths greater than 100 μm. Cellular and nuclear membranes of keratinocytes of the skin were visualised by the use of acridine orange and DIOC5(3). Imaging of the skin after injection of FITC-dextran revealed an extensive network of blood vessels with a size range up to 20 μm. Blood cells could be seen moving through dermal vessels and the blood circulation through the dermal vascular bed was video-taped. The fluorescent dye 4-di-2-ASP showed the presence of nerves fibres around the hair follicles and subsurface blood vessels. Comparison was made between images obtained in vivo using FOCI and in vitro scanning electron microscopy and conventional histology. FOCI offers the potential to study dynamic events in vivo, such as blood flow, skin growth, nerve regeneration and many pathological processes, in ways which have not previously been possible. PMID:9643419

  17. Mathematical Modeling of Bingham Plastic Model of Blood Flow Through Stenotic Vessel

    OpenAIRE

    S.R. Verma

    2014-01-01

    The aim of the present paper is to study the axially symmetric, laminar, steady, one-dimensional flow of blood through narrow stenotic vessel. Blood is considered as Bingham plastic fluid. The analytical results such as pressure drop, resistance to flow and wall shear stress have been obtained. Effect of yield stress and shape of stenosis on resistance to flow and wall shear stress have been discussed through tables and graphically. It has been shown that resistance to flow and th...

  18. Segmentation of retinal blood vessels for detection of diabetic retinopathy: A review

    Directory of Open Access Journals (Sweden)

    Rezty Amalia Aras

    2016-05-01

    Full Text Available Diabetic detinopathy (DR is effect of diabetes mellitus to the human vision that is the major cause of blindness. Early diagnosis of DR is an important requirement in diabetes treatment. Retinal fundus image is commonly used to observe the diabetic retinopathy symptoms. It can present retinal features such as blood vessel and also capture the pathologies which may lead to DR. Blood vessel is one of retinal features which can show the retina pathologies. It can be extracted from retinal image by image processing with following stages: pre-processing, segmentation, and post-processing. This paper contains a review of public retinal image dataset and several methods from various conducted researches. All discussed methods are applicable to each researcher cases. There is no further analysis to conclude the best method which can be used for general cases. However, we suggest morphological and multiscale method that gives the best accuracy in segmentation.

  19. Effect of loading-dose ticagrelor on coronary blood flow, left ventricular remodeling and myocardial enzyme spectrum in patients with acute myocardial infarction after interventional therapy

    Directory of Open Access Journals (Sweden)

    Xiao-Rui Xie

    2016-12-01

    Full Text Available Objective: To study the effect of loading-dose ticagrelor on coronary blood flow, left ventricular remodeling and myocardial enzyme spectrum in patients with acute myocardial infarction after interventional therapy. Methods: A total of 86 patients with acute myocardial infarction who received emergency PCI in our hospital between May 2013 and May 2016 were selected and randomly divided into two groups, ticagrelor group received perioperative ticagrelor therapy and clopidogrel group received perioperative clopidogrel therapy. After PCI, coronary blood flow reperfusion was evaluated, serum myocardial remodeling indexes and myocardial enzymes were determined, and cardiac color Doppler ultrasonography was conducted to determine the cardiac function indexes. Results: TIMI grading and TMPG grading of ticagrelor group after PCI were significantly higher than those of clopidogrel group; serum MMP9, BNP, CITP, PICP, PIIINP, CK, CK-MB, cTnI and cTnT content of ticagrelor group 24h after operation were significantly lower than those of clopidogrel group; LVEDD, LVSED and LVMI of ticagrelor group 2 weeks after operation were significantly lower than those of clopidogrel group while LVEF was significantly higher than that of clopidogrel group. Conclusion: Peri-PCI loading-dose ticagrelor can improve coronary blood perfusion and reduce ventricular remodeling and myocardial injury in patients with acute myocardial infarction.

  20. Automated artery-venous classification of retinal blood vessels based on structural mapping method

    Science.gov (United States)

    Joshi, Vinayak S.; Garvin, Mona K.; Reinhardt, Joseph M.; Abramoff, Michael D.

    2012-03-01

    Retinal blood vessels show morphologic modifications in response to various retinopathies. However, the specific responses exhibited by arteries and veins may provide a precise diagnostic information, i.e., a diabetic retinopathy may be detected more accurately with the venous dilatation instead of average vessel dilatation. In order to analyze the vessel type specific morphologic modifications, the classification of a vessel network into arteries and veins is required. We previously described a method for identification and separation of retinal vessel trees; i.e. structural mapping. Therefore, we propose the artery-venous classification based on structural mapping and identification of color properties prominent to the vessel types. The mean and standard deviation of each of green channel intensity and hue channel intensity are analyzed in a region of interest around each centerline pixel of a vessel. Using the vector of color properties extracted from each centerline pixel, it is classified into one of the two clusters (artery and vein), obtained by the fuzzy-C-means clustering. According to the proportion of clustered centerline pixels in a particular vessel, and utilizing the artery-venous crossing property of retinal vessels, each vessel is assigned a label of an artery or a vein. The classification results are compared with the manually annotated ground truth (gold standard). We applied the proposed method to a dataset of 15 retinal color fundus images resulting in an accuracy of 88.28% correctly classified vessel pixels. The automated classification results match well with the gold standard suggesting its potential in artery-venous classification and the respective morphology analysis.

  1. Progenitor cells in pulmonary vascular remodeling

    Science.gov (United States)

    Yeager, Michael E.; Frid, Maria G.; Stenmark, Kurt R.

    2011-01-01

    Pulmonary hypertension is characterized by cellular and structural changes in the walls of pulmonary arteries. Intimal thickening and fibrosis, medial hypertrophy and fibroproliferative changes in the adventitia are commonly observed, as is the extension of smooth muscle into the previously non-muscularized vessels. A majority of these changes are associated with the enhanced presence of α-SM-actin+ cells and inflammatory cells. Atypical abundances of functionally distinct endothelial cells, particularly in the intima (plexiform lesions), and also in the perivascular regions, are also described. At present, neither the origin(s) of these cells nor the molecular mechanisms responsible for their accumulation, in any of the three compartments of the vessel wall, have been fully elucidated. The possibility that they arise from either resident vascular progenitors or bone marrow–derived progenitor cells is now well established. Resident vascular progenitor cells have been demonstrated to exist within the vessel wall, and in response to certain stimuli, to expand and express myofibroblastic, endothelial or even hematopoietic markers. Bone marrow–derived or circulating progenitor cells have also been shown to be recruited to sites of vascular injury and to assume both endothelial and SM-like phenotypes. Here, we review the data supporting the contributory role of vascular progenitors (including endothelial progenitor cells, smooth muscle progenitor cells, pericytes, and fibrocytes) in vascular remodeling. A more complete understanding of the processes by which progenitor cells modulate pulmonary vascular remodeling will undoubtedly herald a renaissance of therapies extending beyond the control of vascular tonicity and reduction of pulmonary artery pressure. PMID:22034593

  2. Detection of Blood Vessels in Color Fundus Images using a Local Radon Transform

    Directory of Open Access Journals (Sweden)

    Reza Pourreza

    2010-09-01

    Full Text Available Introduction: This paper addresses a method for automatic detection of blood vessels in color fundus images which utilizes two main tools: image partitioning and local Radon transform. Material and Methods: The input images are firstly divided into overlapping windows and then the Radon transform is applied to each. The maximum of the Radon transform in each window corresponds to the probable available sub-vessel. To verify the detected sub-vessel, the maximum is compared with a predefined threshold. The verified sub-vessels are reconstructed using the Radon transform information. All detected and reconstructed sub-vessels are finally combined to make the final vessel tree. Results: The algorithm’s performance was evaluated numerically by applying it to 40 images of DRIVE database, a standard retinal image database. The vessels were extracted manually by two physicians. This database was used to test and compare the available and proposed algorithms for vessel detection in color fundus images. By comparing the output of the algorithm with the manual results, the two parameters TPR and FPR were calculated for each image and the average of TPRs and FPRs were used to plot the ROC curve. Discussion and Conclusion: Comparison of the ROC curve of this algorithm with other algorithms demonstrated the high achieved accuracy. Beside the high accuracy, the Radon transform which is integral-based makes the algorithm robust against noise.

  3. Does Physical Fitness Buffer the Relationship between Psychosocial Stress, Retinal Vessel Diameters, and Blood Pressure among Primary Schoolchildren?

    Science.gov (United States)

    Endes, Katharina; Herrmann, Christian; Colledge, Flora; Brand, Serge; Donath, Lars; Faude, Oliver; Pühse, Uwe; Hanssen, Henner; Zahner, Lukas

    2016-01-01

    Background. Strong evidence exists showing that psychosocial stress plays an important part in the development of cardiovascular diseases. Because physical inactivity is associated with less favourable retinal vessel diameter and blood pressure profiles, this study explores whether physical fitness is able to buffer the negative effects of psychosocial stress on retinal vessel diameters and blood pressure in young children. Methods. 325 primary schoolchildren (51% girls, Mage = 7.28 years) took part in this cross-sectional research project. Retinal arteriolar diameters, retinal venular diameters, arteriolar to venular ratio, and systolic and diastolic blood pressure were assessed in all children. Interactions terms between physical fitness (performance in the 20 m shuttle run test) and four indicators of psychosocial stress (parental reports of critical life events, family, peer and school stress) were tested in a series of hierarchical regression analyses. Results. Critical life events and family, peer, and school-related stress were only weakly associated with retinal vessel diameters and blood pressure. No support was found for a stress-buffering effect of physical fitness. Conclusion. More research is needed with different age groups to find out if and from what age physical fitness can protect against arteriolar vessel narrowing and the occurrence of other cardiovascular disease risk factors. PMID:27795958

  4. Blood Vessel Extraction in Color Retinal Fundus Images with Enhancement Filtering and Unsupervised Classification

    Directory of Open Access Journals (Sweden)

    Zafer Yavuz

    2017-01-01

    Full Text Available Retinal blood vessels have a significant role in the diagnosis and treatment of various retinal diseases such as diabetic retinopathy, glaucoma, arteriosclerosis, and hypertension. For this reason, retinal vasculature extraction is important in order to help specialists for the diagnosis and treatment of systematic diseases. In this paper, a novel approach is developed to extract retinal blood vessel network. Our method comprises four stages: (1 preprocessing stage in order to prepare dataset for segmentation; (2 an enhancement procedure including Gabor, Frangi, and Gauss filters obtained separately before a top-hat transform; (3 a hard and soft clustering stage which includes K-means and Fuzzy C-means (FCM in order to get binary vessel map; and (4 a postprocessing step which removes falsely segmented isolated regions. The method is tested on color retinal images obtained from STARE and DRIVE databases which are available online. As a result, Gabor filter followed by K-means clustering method achieves 95.94% and 95.71% of accuracy for STARE and DRIVE databases, respectively, which are acceptable for diagnosis systems.

  5. Morphological changes of cerebral vessels and expression patterns of MMP-2 and MMP-9 on cerebrovascular wall of alcoholic rats.

    Science.gov (United States)

    Qi, Qian; Liu, Xia; Zhang, Guozhong; He, Wenjing; Ma, Rufei; Cong, Bin; Li, Yingmin

    2014-01-01

    Alcohol abuse increases the incidence of cerebral accidents, which correlates with cerebrovascular structural changes. The present study was designed to observe the cerebrovascular remodeling of drinking rats with light microscopy and transmission electron microscopy (TEM). Short-term alcohol administration induced apparent amplification of perivascular spaces around small vessels in brain tissue, while long-term administration caused pathological changes of basilar arteries (BAs), including endothelial exfoliation, inner elastic lamina (IEL) fragmentation and thickening of tunica media and adventitia. In addition, the relationship between cerebrovascular remodeling and MMP-2 and MMP-9 synthesized by endothelial cells and vascular smooth muscle cells was explored by immunohistochemistry. The two protein expression in cerebral vessels changed dynamically, peaking at 1-2 weeks after treatment, and decreasing as treatment continued. These results suggest that MMP-2 and MMP-9 may play a significant role in blood-brain barrier disruption after alcohol abuse. But the chronic changes of cerebral arteries resulted from drinking are not coincident with time course of MMP-2 and MMP-9 expression in situ.

  6. A computational study for investigating acoustic streaming and tissue heating during high intensity focused ultrasound through blood vessel with an obstacle

    Science.gov (United States)

    Parvin, Salma; Sultana, Aysha

    2017-06-01

    The influence of High Intensity Focused Ultrasound (HIFU) on the obstacle through blood vessel is studied numerically. A three-dimensional acoustics-thermal-fluid coupling model is employed to compute the temperature field around the obstacle through blood vessel. The model construction is based on the linear Westervelt and conjugate heat transfer equations for the obstacle through blood vessel. The system of equations is solved using Finite Element Method (FEM). We found from this three-dimensional numerical study that the rate of heat transfer is increasing from the obstacle and both the convective cooling and acoustic streaming can considerably change the temperature field.

  7. Different Effects of Implanting Sensory Nerve or Blood Vessel on the Vascularization, Neurotization, and Osteogenesis of Tissue-Engineered Bone In Vivo

    Science.gov (United States)

    Fan, Jun-jun; Mu, Tian-wang; Qin, Jun-jun; Bi, Long; Pei, Guo-xian

    2014-01-01

    To compare the different effects of implanting sensory nerve tracts or blood vessel on the osteogenesis, vascularization, and neurotization of the tissue-engineered bone in vivo, we constructed the tissue engineered bone and implanted the sensory nerve tracts (group SN), blood vessel (group VB), or nothing (group Blank) to the side channel of the bone graft to repair the femur defect in the rabbit. Better osteogenesis was observed in groups SN and VB than in group Blank, and no significant difference was found between groups SN and VB at 4, 8, and 12 weeks postoperatively. The neuropeptides expression and the number of new blood vessels in the bone tissues were increased at 8 weeks and then decreased at 12 weeks in all groups and were highest in group VB and lowest in group Blank at all three time points. We conclude that implanting either blood vessel or sensory nerve tract into the tissue-engineered bone can significantly enhance both the vascularization and neurotization simultaneously to get a better osteogenesis effect than TEB alone, and the method of implanting blood vessel has a little better effect of vascularization and neurotization but almost the same osteogenesis effect as implanting sensory nerve. PMID:25101279

  8. Histomorphometric comparative study of blood vessels and their pattern in follicular cyst, odontogenic keratocyst, and ameloblastoma.

    Science.gov (United States)

    Seifi, Safora; Feizi, Farideh; Khafri, Thoraya; Aram, Mehrdad

    2013-03-01

    The present study aimed at assessment and histomorphometric analysis of intratumoral and peritumoral (cystic) blood vessels in odontogenic lesions and their pattern on their clinical behavior by immunohistochemistry and morphometry. In a descriptive and analytical cross-sectional study, 45 paraffin blocks of ameloblastoma, odontogenic keratocyst, and follicular cyst were selected and stained immunohistochemically for CD34. In each slide, images of 3 microscopic fields with the highest microvessel density in intratumoral and peritumoral (cystic) areas were captured at 40× magnification with attached camera system. Inner vascular diameter (IVD) and outer vascular diameter (OVD), cross-sectional area (CSA), and the wall thickness (WT) of the vessels were measured with Motic Plus 2 software. The vascular pattern in odontogenic lesions was analyzed. Outer vascular diameter, IVD, and CSA of the vessels in peritumoral (cystic) areas were greater in ameloblastoma than keratocyst (P = 0.001) and follicular cyst (P keratocyst and follicular cyst. Morphometric specifications of blood vessels (IVD, OVD, CSA) and their pattern in peritumoral (cystic) areas may influence the aggressive clinical behavior of ameloblastoma in comparison with keratocyst and follicular cyst.

  9. Did antepartum hypoxic insult caused by fetal vessel thrombosis influence the procalcitonin level in umbilical blood? A case report.

    Science.gov (United States)

    Kaneko, Masatoki; Yamauchi, Aya; Yamashita, Rie; Sato, Yuichiro; Kodama, Yuki; Sameshima, Hiroshi

    2015-11-01

    We report a case of marked elevation of the procalcitonin level in umbilical blood and neonatal blood at birth. The mother did not perceive fetal motion. Antepartum fetal heart rate monitoring showed a loss of variability and absence of acceleration. No fetal breathing movement, fetal movement, or fetal tone were observed by ultrasonography. The female neonate was delivered by cesarean section at 25 weeks of gestation, with birthweight 774 g. The umbilical arterial pH value at birth was 7.29. Mild elevation in interleukin-6 and tumor necrosis factor-α in umbilical blood were observed. Cytochrome c showed a high level in umbilical and neonatal blood at birth. Placental histopathology revealed multiple fetal vessel thrombosis in the large stem villi and chorionic vessels. The neonate showed no infectious signs throughout the neonatal period. Computed tomography at 3 months of age revealed atrophy in the cerebrum and cerebellum. At 1 year after birth, the infant showed spastic quadriplegia. In this case, antepartum asphyxia due to fetal vessel thrombosis may have influenced the elevation of procalcitonin level in umbilical blood and neonatal blood at birth. © 2015 Japan Society of Obstetrics and Gynecology.

  10. Impact of short-term treatment with telmisartan on cerebral arterial remodeling in SHR.

    Directory of Open Access Journals (Sweden)

    Sébastien Foulquier

    Full Text Available Chronic hypertension decreases internal diameter of cerebral arteries and arterioles. We recently showed that short-term treatment with the angiotensin II receptor blocker telmisartan restored baseline internal diameter of small cerebral arterioles in spontaneously hypertensive rats (SHR, via reversal of structural remodeling and inhibition of the angiotensin II vasoconstrictor response. As larger arteries also participate in the regulation of cerebral circulation, we evaluated whether similar short-term treatment affects middle cerebral arteries of SHR.Baseline internal diameters of pressurised middle cerebral arteries from SHR and their respective controls, Wistar Kyoto rats (WKY and responses to angiotensin II were studied in a small vessel arteriograph. Pressure myogenic curves and passive internal diameters were measured following EDTA deactivation, and elastic modulus from stress-strain relationships.Active baseline internal diameter was 23% lower in SHR compared to WKY, passive internal diameter (EDTA 28% lower and elastic modulus unchanged. Pressure myogenic curves were shifted to higher pressure values in SHR. Telmisartan lowered blood pressure but had no effect on baseline internal diameter nor on structural remodeling (passive internal diameter and elastic modulus remained unchanged compared to SHR. Telmisartan shifted the pressure myogenic curve to lower pressure values than SHR.In the middle cerebral arteries of SHR, short-term treatment with telmisartan had no effect on structural remodeling and did not restore baseline internal diameter, but allowed myogenic tone to adapt towards lower pressure values.

  11. Blood vessel classification into arteries and veins in retinal images

    Science.gov (United States)

    Kondermann, Claudia; Kondermann, Daniel; Yan, Michelle

    2007-03-01

    The prevalence of diabetes is expected to increase dramatically in coming years; already today it accounts for a major proportion of the health care budget in many countries. Diabetic Retinopathy (DR), a micro vascular complication very often seen in diabetes patients, is the most common cause of visual loss in working age population of developed countries today. Since the possibility of slowing or even stopping the progress of this disease depends on the early detection of DR, an automatic analysis of fundus images would be of great help to the ophthalmologist due to the small size of the symptoms and the large number of patients. An important symptom for DR are abnormally wide veins leading to an unusually low ratio of the average diameter of arteries to veins (AVR). There are also other diseases like high blood pressure or diseases of the pancreas with one symptom being an abnormal AVR value. To determine it, a classification of vessels as arteries or veins is indispensable. As to our knowledge despite the importance there have only been two approaches to vessel classification yet. Therefore we propose an improved method. We compare two feature extraction methods and two classification methods based on support vector machines and neural networks. Given a hand-segmentation of vessels our approach achieves 95.32% correctly classified vessel pixels. This value decreases by 10% on average, if the result of a segmentation algorithm is used as basis for the classification.

  12. Retinal hemodynamic oxygen reactivity assessed by perfusion velocity, blood oximetry and vessel diameter measurements

    DEFF Research Database (Denmark)

    Klefter, Oliver Niels; Lauritsen, Anne Øberg; Larsen, Michael

    2015-01-01

    PURPOSE: To test the oxygen reactivity of a fundus photographic method of measuring macular perfusion velocity and to integrate macular perfusion velocities with measurements of retinal vessel diameters and blood oxygen saturation. METHODS: Sixteen eyes in 16 healthy volunteers were studied at two...... is a valid method for assessing macular perfusion. Results were consistent with previous observations of hyperoxic blood flow reduction using blue field entoptic and laser Doppler velocimetry. Retinal perfusion seemed to be regulated around individual set points according to blood glucose levels. Multimodal...

  13. [Topography of the blood vessels in the hilum of the kidney of Myrmecophaga tridactyla].

    Science.gov (United States)

    Souza, W M; Miglino, M A; Arantes, I G; Nascimento, A A

    1991-01-01

    The study was undertaken in 10 formol-imbibed kidneys of great anteater (Myrmecophaga tridactyla). After the dissection the following characteristics were showed: kidney blood vessels are distributed in 2 different sites, namely hilar and extrahilar, amounting 3 to 6 in the right side 3 to 7 in the left side. Arterial branches in extrahilar region range from 1 to 2 in both sides and in hilar region they present from 1 to 4 in the right and 1 to 2 in the left. Venous roots occur in 1 to 2 vessels in the right and 1 to 3 vessels in the left, occupying only the hilar region, except one case where it was present in the right side.

  14. Heterogeneity of muscarinic receptor subtypes in cerebral blood vessels

    International Nuclear Information System (INIS)

    Garcia-Villalon, A.L.; Krause, D.N.; Ehlert, F.J.; Duckles, S.P.

    1991-01-01

    The identity and distribution of muscarinic cholinergic receptor subtypes and associated signal transduction mechanisms was characterized for the cerebral circulation using correlated functional and biochemical investigations. Subtypes were distinguished by the relative affinities of a panel of muscarinic antagonists, pirenzepine, AF-DX 116 [11-2-[[2-[diethylaminomethyl]- 1-piperidinyl]acetyl]-5,11-dihydro-6H- pyrido[2,3-b][1,4]benzodiazepine-6-one], hexahydrosiladifenidol, methoctramine, 4-diphenylacetoxy-N-methylpiperidine methobromide, dicyclomine, para-fluoro-hexahydrosiladifenidol and atropine. Muscarinic receptors characterized by inhibition of [3H]quinuclidinylbenzilate binding in membranes of bovine pial arteries were of the M2 subtype. In contrast pharmacological analysis of [3H]-quinuclidinylbenzilate binding in bovine intracerebral microvessels suggests the presence of an M4 subtype. Receptors mediating endothelium-dependent vasodilation in rabbit pial arteries were of the M3 subtype, whereas muscarinic receptors stimulating endothelium-independent phosphoinositide hydrolysis in bovine pial arteries were of the M1 subtype. These findings suggest that characteristics of muscarinic receptors in cerebral blood vessels vary depending on the type of vessel, cellular location and function mediated

  15. Imaging transient blood vessel fusion events in zebrafish by correlative volume electron microscopy.

    Directory of Open Access Journals (Sweden)

    Hannah E J Armer

    Full Text Available The study of biological processes has become increasingly reliant on obtaining high-resolution spatial and temporal data through imaging techniques. As researchers demand molecular resolution of cellular events in the context of whole organisms, correlation of non-invasive live-organism imaging with electron microscopy in complex three-dimensional samples becomes critical. The developing blood vessels of vertebrates form a highly complex network which cannot be imaged at high resolution using traditional methods. Here we show that the point of fusion between growing blood vessels of transgenic zebrafish, identified in live confocal microscopy, can subsequently be traced through the structure of the organism using Focused Ion Beam/Scanning Electron Microscopy (FIB/SEM and Serial Block Face/Scanning Electron Microscopy (SBF/SEM. The resulting data give unprecedented microanatomical detail of the zebrafish and, for the first time, allow visualization of the ultrastructure of a time-limited biological event within the context of a whole organism.

  16. Nestin upregulation characterizes vascular remodeling secondary to hypertension in the rat.

    Science.gov (United States)

    Tardif, Kim; Hertig, Vanessa; Duquette, Natacha; Villeneuve, Louis; El-Hamamsy, Ismail; Tanguay, Jean-François; Calderone, Angelino

    2015-05-15

    Proliferation and hypertrophy of vascular smooth muscle cells represent hallmark features of vessel remodeling secondary to hypertension. The intermediate filament protein nestin was recently identified in vascular smooth muscle cells and in other cell types directly participated in proliferation. The present study tested the hypothesis that vessel remodeling secondary to hypertension was characterized by nestin upregulation in vascular smooth muscle cells. Two weeks after suprarenal abdominal aorta constriction of adult male Sprague-Dawley rats, elevated mean arterial pressure increased the media area and thickness of the carotid artery and aorta and concomitantly upregulated nestin protein levels. In the normal adult rat carotid artery, nestin immunoreactivity was observed in a subpopulation of vascular smooth muscle cells, and the density significantly increased following suprarenal abdominal aorta constriction. Filamentous nestin was detected in cultured rat carotid artery- and aorta-derived vascular smooth muscle cells and an analogous paradigm observed in human aorta-derived vascular smooth muscle cells. ANG II and EGF treatment of vascular smooth muscle cells stimulated DNA and protein synthesis and increased nestin protein levels. Lentiviral short-hairpin RNA-mediated nestin depletion of carotid artery-derived vascular smooth muscle cells inhibited peptide growth factor-stimulated DNA synthesis, whereas protein synthesis remained intact. These data have demonstrated that vessel remodeling secondary to hypertension was characterized in part by nestin upregulation in vascular smooth muscle cells. The selective role of nestin in peptide growth factor-stimulated DNA synthesis has revealed that the proliferative and hypertrophic responses of vascular smooth muscle cells were mediated by divergent signaling events. Copyright © 2015 the American Physiological Society.

  17. Impact of peri-stent remodeling on restenosis: a volumetric intravascular ultrasound study.

    Science.gov (United States)

    Nakamura, M; Yock, P G; Bonneau, H N; Kitamura, K; Aizawa, T; Tamai, H; Fitzgerald, P J; Honda, Y

    2001-05-01

    Vessel remodeling is an important mechanism of late lumen loss after nonstent coronary interventions. However, its impact on in-stent restenosis has not been systematically investigated. Serial volumetric intravascular ultrasound analyses (poststent and follow-up) were performed in 55 lesions treated with a balloon-expandable stent (ACS MultiLink) using standard stent deployment techniques. The vessel volume (VV), lumen volume (LV), and volume bordered by the stent (SV) were measured using Simpson's method. The volume of plaque and neointima outside the stent (peri-stent volume, PSV) and volume of neointima within the stent (intrastent volume) were also measured. The change of each parameter during the follow-up period (follow-up minus poststent) was calculated and then divided by SV to normalize these values (designated as percent change [%]). As expected, %PSV directly correlated with %VV (Pexterior to a coronary stent occurs to a variable degree after stent implantation. There is a distinct trade-off between positive remodeling and in-stent hyperplasia: in segments in which the degree of peri-stent remodeling is less, intrastent neointimal proliferation is greater and accompanied by more significant late lumen loss.

  18. A Strategy for Rapid Construction of Blood Vessel-Like Structures with Complex Cell Alignments.

    Science.gov (United States)

    Wang, Nuoxin; Peng, Yunhu; Zheng, Wenfu; Tang, Lixue; Cheng, Shiyu; Yang, Junchuan; Liu, Shaoqin; Zhang, Wei; Jiang, Xingyu

    2018-04-17

    A method is developed that can rapidly produce blood vessel-like structures by bonding cell-laden electrospinning (ES) films layer by layer using fibrin glue within 90 min. This strategy allows control of cell type, cell orientation, and material composition in separate layers. Furthermore, ES films with thicker fibers (polylactic-co-glycolic acid, fiber diameter: ≈3.7 µm) are used as cell-seeding layers to facilitate the cell in-growth; those with thinner fibers (polylactic acid, fiber diameter: ≈1.8 µm) are used as outer reinforcing layers to improve the mechanical strength and reduce the liquid leakage of the scaffold. Cells grow, proliferate, and migrate well in the multilayered structure. This design aims at a new type of blood vessel substitute with flexible control of parameters and implementation of functions. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Impaired flow-induced arterial remodeling in DOCA-salt hypertensive rats

    DEFF Research Database (Denmark)

    Lemkens, Pieter; Nelissen, Jelly; Meens, Merlijn J P M T

    2012-01-01

    Arteries from young healthy animals respond to chronic changes in blood flow and blood pressure by structural remodeling. We tested whether the ability to respond to decreased (-90%) or increased (+100%) blood flow is impaired during the development of deoxycorticosterone acetate (DOCA)-salt hype...

  20. Caveolin1 Is Required for Th1 Cell Infiltration, but Not Tight Junction Remodeling, at the Blood-Brain Barrier in Autoimmune Neuroinflammation

    Directory of Open Access Journals (Sweden)

    Sarah E. Lutz

    2017-11-01

    Full Text Available Lymphocytes cross vascular boundaries via either disrupted tight junctions (TJs or caveolae to induce tissue inflammation. In the CNS, Th17 lymphocytes cross the blood-brain barrier (BBB before Th1 cells; yet this differential crossing is poorly understood. We have used intravital two-photon imaging of the spinal cord in wild-type and caveolae-deficient mice with fluorescently labeled endothelial tight junctions to determine how tight junction remodeling and caveolae regulate CNS entry of lymphocytes during the experimental autoimmune encephalomyelitis (EAE model for multiple sclerosis. We find that dynamic tight junction remodeling occurs early in EAE but does not depend upon caveolar transport. Moreover, Th1, but not Th17, lymphocytes are significantly reduced in the inflamed CNS of mice lacking caveolae. Therefore, tight junction remodeling facilitates Th17 migration across the BBB, whereas caveolae promote Th1 entry into the CNS. Moreover, therapies that target both tight junction degradation and caveolar transcytosis may limit lymphocyte infiltration during inflammation.

  1. Effects of exercise training on pulmonary vessel muscularization and right ventricular function in an animal model of COPD

    OpenAIRE

    Hassel, Erlend; Berre, Anne Marie; Skjulsvik, Anne Jarstein; Steinshamn, Sigurd

    2014-01-01

    Background Right ventricular dysfunction in COPD is common, even in the absence of pulmonary hypertension. The aim of the present study was to examine the effects of high intensity interval training (HIIT) on right ventricular (RV) function, as well as pulmonary blood vessel remodeling in a mouse model of COPD. Methods 42 female A/JOlaHsd mice were randomized to exposure to either cigarette smoke or air for 6 hours/day, 5 days/week for 14 weeks. Mice from both groups were further randomized t...

  2. Rapid sealing of porcine renal blood vessels, ex vivo, using a high power, 1470-nm laser, and laparoscopic prototype

    Science.gov (United States)

    Hardy, Luke A.; Hutchens, Thomas C.; Larson, Eric R.; Gonzalez, David A.; Chang, Chun-Hung; Nau, William H.; Fried, Nathaniel M.

    2017-05-01

    Energy-based, radiofrequency (RF) and ultrasonic (US) devices currently provide rapid sealing of blood vessels during laparoscopic procedures. We are exploring infrared lasers as an alternate energy modality for vessel sealing, capable of generating less collateral thermal damage. Previous studies demonstrated feasibility of sealing vessels in an in vivo porcine model using a 1470-nm laser. However, the initial prototype was designed for testing in open surgery and featured tissue clasping and light delivery mechanisms incompatible with laparoscopic surgery. In this study, a laparoscopic prototype similar to devices currently in surgical use was developed, and performance tests were conducted on porcine renal blood vessels, ex vivo. The 5-mm outer-diameter laparoscopic prototype featured a traditional Maryland jaw configuration that enables tissue manipulation and blunt dissection. Laser energy was delivered through a 550-μm-core-diameter optical fiber with side-delivery from the lower jaw and beam dimensions of 18-mm length×1.2-mm width. The 1470-nm diode laser delivered 68 W with 3-s activation time, consistent with vessel seal times associated with RF and US-based devices. A total of 69 fresh porcine renal vessels with mean diameter of 3.3±1.7 mm were tested, ex vivo. Vessels smaller than 5-mm diameter were consistently sealed (48/51) with burst pressures greater than malignant hypertension blood pressure (180 mmHg), averaging 1038±474 mmHg. Vessels larger than 5 mm were not consistently sealed (6/18), yielding burst pressures of only 174±221 mmHg. Seal width, thermal damage zone, and thermal spread averaged 1.7±0.8, 3.4±0.7, and 1.0±0.4 mm, respectively. Results demonstrated that the 5-mm optical laparoscopic prototype consistently sealed vessels less than 5-mm diameter with low thermal spread. Further in vivo studies are planned to test the performance across a variety of vessels and tissues.

  3. Limitations of quantitative photoacoustic measurements of blood oxygenation in small vessels

    International Nuclear Information System (INIS)

    Sivaramakrishnan, Mathangi; Maslov, Konstantin; Zhang, Hao F; Stoica, George; Wang, Lihong V

    2007-01-01

    We investigate the feasibility of obtaining accurate quantitative information, such as local blood oxygenation level (sO 2 ), with a spatial resolution of about 50 μm from spectral photoacoustic (PA) measurements. The optical wavelength dependence of the peak values of the PA signals is utilized to obtain the local blood oxygenation level. In our in vitro experimental models, the PA signal amplitude is found to be linearly proportional to the blood optical absorption coefficient when using ultrasonic transducers with central frequencies high enough such that the ultrasonic wavelengths are shorter than the light penetration depth into the blood vessels. For an optical wavelength in the 578-596 nm region, with a transducer central frequency that is above 25 MHz, the sensitivity and accuracy of sO 2 inversion is shown to be better than 4%. The effect of the transducer focal position on the accuracy of quantifying blood oxygenation is found to be negligible. In vivo oxygenation measurements of rat skin microvasculature yield results consistent with those from in vitro studies, although factors specific to in vivo measurements, such as the spectral dependence of tissue optical attenuation, dramatically affect the accuracy of sO 2 quantification in vivo

  4. Modeling the Role of the Glymphatic Pathway and Cerebral Blood Vessel Properties in Alzheimer's Disease Pathogenesis.

    Science.gov (United States)

    Kyrtsos, Christina Rose; Baras, John S

    2015-01-01

    Alzheimer's disease (AD) is the most common cause of dementia in the elderly, affecting over 10% population over the age of 65 years. Clinically, AD is described by the symptom set of short term memory loss and cognitive decline, changes in mentation and behavior, and eventually long-term memory deficit as the disease progresses. On imaging studies, significant atrophy with subsequent increase in ventricular volume have been observed. Pathology on post-mortem brain specimens demonstrates the classic findings of increased beta amyloid (Aβ) deposition and the presence of neurofibrillary tangles (NFTs) within affected neurons. Neuroinflammation, dysregulation of blood-brain barrier transport and clearance, deposition of Aβ in cerebral blood vessels, vascular risk factors such as atherosclerosis and diabetes, and the presence of the apolipoprotein E4 allele have all been identified as playing possible roles in AD pathogenesis. Recent research has demonstrated the importance of the glymphatic system in the clearance of Aβ from the brain via the perivascular space surrounding cerebral blood vessels. Given the variety of hypotheses that have been proposed for AD pathogenesis, an interconnected, multilayer model offers a unique opportunity to combine these ideas into a single unifying model. Results of this model demonstrate the importance of vessel stiffness and heart rate in maintaining adequate clearance of Aβ from the brain.

  5. Comparison of the number of gingival blood vessels between type 2 diabetes mellitus and chronic periodontitis patients: An immunohistological study

    Directory of Open Access Journals (Sweden)

    Gautami Subhadra Penmetsa

    2015-01-01

    Full Text Available Background: The relationship between diabetes and periodontitis has been studied for more than 50 years and is generally agreed that the periodontal disease is more prevalent in diabetic patients compared to nondiabetics. Vascular changes like increased thickness of basement membrane in small vessels has been reported in diabetic patients, but the quantity of blood vessels in gingiva of diabetic patients has not been discussed much. The aim of this study was to compare the number of blood vessels in gingiva between chronic periodontitis (CP patients, CP with diabetes (type 2, and normal healthy gingiva. Materials and Methods: The study included 75 patients, divided into three groups of 25 patients each-Group I with healthy periodontium (HP, Group II with CP, and Group III with CP with diabetes mellitus (CPDM.Gingival biopsies were obtained from the subjects undergoing crown lengthening procedure for Group I, and in patients with CP and in CPDM biopsies were collected from teeth undergoing extraction. Sections were prepared for immune histochemical staining with CD34. Results: Difference was observed in the average number of blood vessels when compared between HP, CP, and CPDM groups. Statistical significant difference was observed when the HP and CP groups and HP and CPDM groups were compared. Conclusion: The results of the study indicated that the number of blood vessels in gingival connective tissue is significantly higher in CP and CPDM patients.

  6. Smooth Muscle Endothelin B Receptors Regulate Blood Pressure but Not Vascular Function or Neointimal Remodeling.

    Science.gov (United States)

    Miller, Eileen; Czopek, Alicja; Duthie, Karolina M; Kirkby, Nicholas S; van de Putte, Elisabeth E Fransen; Christen, Sibylle; Kimmitt, Robert A; Moorhouse, Rebecca; Castellan, Raphael F P; Kotelevtsev, Yuri V; Kuc, Rhoda E; Davenport, Anthony P; Dhaun, Neeraj; Webb, David J; Hadoke, Patrick W F

    2017-02-01

    The role of smooth muscle endothelin B (ET B ) receptors in regulating vascular function, blood pressure (BP), and neointimal remodeling has not been established. Selective knockout mice were generated to address the hypothesis that loss of smooth muscle ET B receptors would reduce BP, alter vascular contractility, and inhibit neointimal remodeling. ET B receptors were selectively deleted from smooth muscle by crossing floxed ET B mice with those expressing cre-recombinase controlled by the transgelin promoter. Functional consequences of ET B deletion were assessed using myography. BP was measured by telemetry, and neointimal lesion formation induced by femoral artery injury. Lesion size and composition (day 28) were analyzed using optical projection tomography, histology, and immunohistochemistry. Selective deletion of ET B was confirmed by genotyping, autoradiography, polymerase chain reaction, and immunohistochemistry. ET B -mediated contraction was reduced in trachea, but abolished from mesenteric veins, of knockout mice. Induction of ET B -mediated contraction in mesenteric arteries was also abolished in these mice. Femoral artery function was unaltered, and baseline BP modestly elevated in smooth muscle ET B knockout compared with controls (+4.2±0.2 mm Hg; P<0.0001), but salt-induced and ET B blockade-mediated hypertension were unaltered. Circulating endothelin-1 was not altered in knockout mice. ET B -mediated contraction was not induced in femoral arteries by incubation in culture medium or lesion formation, and lesion size was not altered in smooth muscle ET B knockout mice. In the absence of other pathology, ET B receptors in vascular smooth muscle make a small but significant contribution to ET B -dependent regulation of BP. These ET B receptors have no effect on vascular contraction or neointimal remodeling. © 2016 The Authors.

  7. X-ray PIV measurement of blood flow in deep vessels of a rat: An in vivo feasibility study.

    Science.gov (United States)

    Park, Hanwook; Yeom, Eunseop; Lee, Sang Joon

    2016-01-18

    X-ray PIV measurement is a noninvasive approach to measure opaque blood flows. However, it is not easy to measure real pulsatile blood flows in the blood vessels located at deep position of the body, because the surrounding tissues significantly attenuate the contrast of X-ray images. This study investigated the effect of surrounding tissues on X-ray beam attenuation by measuring the velocity fields of blood flows in deep vessels of a live rat. The decrease in image contrast was minimized by employing biocompatible CO2 microbubbles as tracer particles. The maximum measurable velocity of blood flows in the abdominal aorta of a rat model was found through comparative examination between the PIV measurement accuracy and the level of image contrast according to the input flow rate. Furthermore, the feasibility of using X-ray PIV to accurately measure in vivo blood flows was demonstrated by determining the velocity field of blood flows in the inferior vena cava of a rat. This study may serve as a reference in conducting in vivo X-ray PIV measurements of pulsatile blood flows in animal disease models and investigating hemodynamic characteristics and circulatory vascular diseases.

  8. Spatial distribution of diffuse, primitive, and classic amyloid-beta deposits and blood vessels in the upper laminae of the frontal cortex in Alzheimer disease.

    Science.gov (United States)

    Armstrong, R A; Cairns, N J; Lantos, P L

    1998-12-01

    The spatial distribution of the diffuse, primitive, and classic amyloid-beta deposits was studied in the upper laminae of the superior frontal gyrus in cases of sporadic Alzheimer disease (AD). Amyloid-beta-stained tissue was counterstained with collagen IV to determine whether the spatial distribution of the amyloid-beta deposits along the cortex was related to blood vessels. In all patients, amyloid-beta deposits and blood vessels were aggregated into distinct clusters and in many patients, the clusters were distributed with a regular periodicity along the cortex. The clusters of diffuse and primitive deposits did not coincide with the clusters of blood vessels in most patients. However, the clusters of classic amyloid-beta deposits coincided with those of the large diameter (>10 microm) blood vessels in all patients and with clusters of small-diameter (upper cortical laminae.

  9. Regulation of tyrosine phosphatases in the adventitia during vascular remodelling

    International Nuclear Information System (INIS)

    Micke, Patrick; Hackbusch, Daniel; Mercan, Sibel; Stawowy, Philipp; Tsuprykov, Oleg; Unger, Thomas; Ostman, Arne; Kappert, Kai

    2009-01-01

    Protein tyrosine phosphatases (PTPs) are regulators of growth factor signalling in vascular remodelling. The aim of this study was to evaluate PTP expression in the context of PDGF-signalling in the adventitia after angioplasty. Utilising a rat carotid artery model, the adventitial layers of injured and non-injured vessels were laser microdissected. The mRNA expression of the PDGF β-receptor, the ligands PDGF-A/B/C/D and the receptor-antagonising PTPs (DEP-1, TC-PTP, SHP-2, PTP1B) were determined and correlated to vascular morphometrics, proliferation markers and PDGF β-receptor phosphorylation. The levels of the PDGF β-receptor, PDGF-C and PDGF-D were upregulated concurrently with the antagonising PTPs DEP-1 and TC-PTP at day 8, and normalised at day 14 after vessel injury. Although the proliferation parameters were time-dependently altered in the adventitial layer, the phosphorylation of the PDGF β-receptor remained unchanged. The expression dynamics of specific PTPs indicate a regulatory role of PDGF-signalling also in the adventitia during vascular remodelling.

  10. Smooth muscle cell recruitment to lymphatic vessels requires PDGFB and impacts vessel size but not identity.

    Science.gov (United States)

    Wang, Yixin; Jin, Yi; Mäe, Maarja Andaloussi; Zhang, Yang; Ortsäter, Henrik; Betsholtz, Christer; Mäkinen, Taija; Jakobsson, Lars

    2017-10-01

    Tissue fluid drains through blind-ended lymphatic capillaries, via smooth muscle cell (SMC)-covered collecting vessels into venous circulation. Both defective SMC recruitment to collecting vessels and ectopic recruitment to lymphatic capillaries are thought to contribute to vessel failure, leading to lymphedema. However, mechanisms controlling lymphatic SMC recruitment and its role in vessel maturation are unknown. Here, we demonstrate that platelet-derived growth factor B (PDGFB) regulates lymphatic SMC recruitment in multiple vascular beds. PDGFB is selectively expressed by lymphatic endothelial cells (LECs) of collecting vessels. LEC-specific deletion of Pdgfb prevented SMC recruitment causing dilation and failure of pulsatile contraction of collecting vessels. However, vessel remodelling and identity were unaffected. Unexpectedly, Pdgfb overexpression in LECs did not induce SMC recruitment to capillaries. This was explained by the demonstrated requirement of PDGFB extracellular matrix (ECM) retention for lymphatic SMC recruitment, and the low presence of PDGFB-binding ECM components around lymphatic capillaries. These results demonstrate the requirement of LEC-autonomous PDGFB expression and retention for SMC recruitment to lymphatic vessels, and suggest an ECM-controlled checkpoint that prevents SMC investment of capillaries, which is a common feature in lymphedematous skin. © 2017. Published by The Company of Biologists Ltd.

  11. Numerical modeling of the pulse wave propagation in large blood vessels based on liquid and wall interaction

    International Nuclear Information System (INIS)

    Rup, K; Dróżdż, A

    2014-01-01

    The purpose of this article is to develop a non-linear, one-dimensional model of pulse wave propagation in the arterial cardiovascular system. The model includes partial differential equations resulting from the balance of mass and momentum for the fluid-filled area and the balance equation for the area of the wall and vessels. The considered mathematical model of pulse wave propagation in the thoracic aorta section takes into account the viscous dissipation of fluid energy, realistic values of parameters describing the physicochemical properties of blood and vessel wall. Boundary and initial conditions contain the appropriate information obtained from in vivo measurements. As a result of the numerical solution of the mass and momentum balance equations for the blood and the equilibrium equation for the arterial wall area, time- dependent deformation, respective velocity profiles and blood pressure were determined.

  12. Numerical Modeling of Interstitial Fluid Flow Coupled with Blood Flow through a Remodeled Solid Tumor Microvascular Network.

    Science.gov (United States)

    Soltani, M; Chen, P

    2013-01-01

    Modeling of interstitial fluid flow involves processes such as fluid diffusion, convective transport in extracellular matrix, and extravasation from blood vessels. To date, majority of microvascular flow modeling has been done at different levels and scales mostly on simple tumor shapes with their capillaries. However, with our proposed numerical model, more complex and realistic tumor shapes and capillary networks can be studied. Both blood flow through a capillary network, which is induced by a solid tumor, and fluid flow in tumor's surrounding tissue are formulated. First, governing equations of angiogenesis are implemented to specify the different domains for the network and interstitium. Then, governing equations for flow modeling are introduced for different domains. The conservation laws for mass and momentum (including continuity equation, Darcy's law for tissue, and simplified Navier-Stokes equation for blood flow through capillaries) are used for simulating interstitial and intravascular flows and Starling's law is used for closing this system of equations and coupling the intravascular and extravascular flows. This is the first study of flow modeling in solid tumors to naturalistically couple intravascular and extravascular flow through a network. This network is generated by sprouting angiogenesis and consisting of one parent vessel connected to the network while taking into account the non-continuous behavior of blood, adaptability of capillary diameter to hemodynamics and metabolic stimuli, non-Newtonian blood flow, and phase separation of blood flow in capillary bifurcation. The incorporation of the outlined components beyond the previous models provides a more realistic prediction of interstitial fluid flow pattern in solid tumors and surrounding tissues. Results predict higher interstitial pressure, almost two times, for realistic model compared to the simplified model.

  13. Numerical Modeling of Interstitial Fluid Flow Coupled with Blood Flow through a Remodeled Solid Tumor Microvascular Network.

    Directory of Open Access Journals (Sweden)

    M Soltani

    Full Text Available Modeling of interstitial fluid flow involves processes such as fluid diffusion, convective transport in extracellular matrix, and extravasation from blood vessels. To date, majority of microvascular flow modeling has been done at different levels and scales mostly on simple tumor shapes with their capillaries. However, with our proposed numerical model, more complex and realistic tumor shapes and capillary networks can be studied. Both blood flow through a capillary network, which is induced by a solid tumor, and fluid flow in tumor's surrounding tissue are formulated. First, governing equations of angiogenesis are implemented to specify the different domains for the network and interstitium. Then, governing equations for flow modeling are introduced for different domains. The conservation laws for mass and momentum (including continuity equation, Darcy's law for tissue, and simplified Navier-Stokes equation for blood flow through capillaries are used for simulating interstitial and intravascular flows and Starling's law is used for closing this system of equations and coupling the intravascular and extravascular flows. This is the first study of flow modeling in solid tumors to naturalistically couple intravascular and extravascular flow through a network. This network is generated by sprouting angiogenesis and consisting of one parent vessel connected to the network while taking into account the non-continuous behavior of blood, adaptability of capillary diameter to hemodynamics and metabolic stimuli, non-Newtonian blood flow, and phase separation of blood flow in capillary bifurcation. The incorporation of the outlined components beyond the previous models provides a more realistic prediction of interstitial fluid flow pattern in solid tumors and surrounding tissues. Results predict higher interstitial pressure, almost two times, for realistic model compared to the simplified model.

  14. An Automatic Cognitive Graph-Based Segmentation for Detection of Blood Vessels in Retinal Images

    Directory of Open Access Journals (Sweden)

    Rasha Al Shehhi

    2016-01-01

    Full Text Available This paper presents a hierarchical graph-based segmentation for blood vessel detection in digital retinal images. This segmentation employs some of perceptual Gestalt principles: similarity, closure, continuity, and proximity to merge segments into coherent connected vessel-like patterns. The integration of Gestalt principles is based on object-based features (e.g., color and black top-hat (BTH morphology and context and graph-analysis algorithms (e.g., Dijkstra path. The segmentation framework consists of two main steps: preprocessing and multiscale graph-based segmentation. Preprocessing is to enhance lighting condition, due to low illumination contrast, and to construct necessary features to enhance vessel structure due to sensitivity of vessel patterns to multiscale/multiorientation structure. Graph-based segmentation is to decrease computational processing required for region of interest into most semantic objects. The segmentation was evaluated on three publicly available datasets. Experimental results show that preprocessing stage achieves better results compared to state-of-the-art enhancement methods. The performance of the proposed graph-based segmentation is found to be consistent and comparable to other existing methods, with improved capability of detecting small/thin vessels.

  15. Inflammation and vascular remodeling in the ventral hippocampus contributes to vulnerability to stress.

    Science.gov (United States)

    Pearson-Leary, J; Eacret, D; Chen, R; Takano, H; Nicholas, B; Bhatnagar, S

    2017-06-27

    During exposure to chronic stress, some individuals engage in active coping behaviors that promote resiliency to stress. Other individuals engage in passive coping that is associated with vulnerability to stress and with anxiety and depression. In an effort to identify novel molecular mechanisms that underlie vulnerability or resilience to stress, we used nonbiased analyses of microRNAs in the ventral hippocampus (vHPC) to identify those miRNAs differentially expressed in active (long-latency (LL)/resilient) or passive (short-latency (SL)/vulnerable) rats following chronic social defeat. In the vHPC of active coping rats, miR-455-3p level was increased, while miR-30e-3p level was increased in the vHPC of passive coping rats. Pathway analyses identified inflammatory and vascular remodeling pathways as enriched by genes targeted by these microRNAs. Utilizing several independent markers for blood vessels, inflammatory processes and neural activity in the vHPC, we found that SL/vulnerable rats exhibit increased neural activity, vascular remodeling and inflammatory processes that include both increased blood-brain barrier permeability and increased number of microglia in the vHPC relative to control and resilient rats. To test the relevance of these changes for the development of the vulnerable phenotype, we used pharmacological approaches to determine the contribution of inflammatory processes in mediating vulnerability and resiliency. Administration of the pro-inflammatory cytokine vascular endothelial growth factor-164 increased vulnerability to stress, while the non-steroidal anti-inflammatory drug meloxicam attenuated vulnerability. Collectively, these results show that vulnerability to stress is determined by a re-designed neurovascular unit characterized by increased neural activity, vascular remodeling and pro-inflammatory mechanisms in the vHPC. These results suggest that dampening inflammatory processes by administering anti-inflammatory agents reduces

  16. Vasotrophic Regulation of Age-Dependent Hypoxic Cerebrovascular Remodeling

    Science.gov (United States)

    Silpanisong, Jinjutha; Pearce, William J.

    2015-01-01

    Hypoxia can induce functional and structural vascular remodeling by changing the expression of trophic factors to promote homeostasis. While most experimental approaches have been focused on functional remodeling, structural remodeling can reflect changes in the abundance and organization of vascular proteins that determine functional remodeling. Better understanding of age-dependent hypoxic macrovascular remodeling processes of the cerebral vasculature and its clinical implications require knowledge of the vasotrophic factors that influence arterial structure and function. Hypoxia can affect the expression of transcription factors, classical receptor tyrosine kinase factors, non-classical G-protein coupled factors, catecholamines, and purines. Hypoxia’s remodeling effects can be mediated by Hypoxia Inducible Factor (HIF) upregulation in most vascular beds, but alterations in the expression of growth factors can also be independent of HIF. PPARγ is another transcription factor involved in hypoxic remodeling. Expression of classical receptor tyrosine kinase ligands, including vascular endothelial growth factor, platelet derived growth factor, fibroblast growth factor and angiopoietins, can be altered by hypoxia which can act simultaneously to affect remodeling. Tyrosine kinase-independent factors, such as transforming growth factor, nitric oxide, endothelin, angiotensin II, catecholamines, and purines also participate in the remodeling process. This adaptation to hypoxic stress can fundamentally change with age, resulting in different responses between fetuses and adults. Overall, these mechanisms integrate to assure that blood flow and metabolic demand are closely matched in all vascular beds and emphasize the view that the vascular wall is a highly dynamic and heterogeneous tissue with multiple cell types undergoing regular phenotypic transformation. PMID:24063376

  17. Nerve growth factor regulates neurolymphatic remodeling during corneal inflammation and resolution.

    Directory of Open Access Journals (Sweden)

    Darci M Fink

    Full Text Available The cellular and physiologic mechanisms that regulate the resolution of inflammation remain poorly defined despite their widespread importance in improving inflammatory disease outcomes. We studied the resolution of two cardinal signs of inflammation-pain and swelling-by investigating molecular mechanisms that regulate neural and lymphatic vessel remodeling during the resolution of corneal inflammation. A mouse model of corneal inflammation and wound recovery was developed to study this process in vivo. Administration of nerve growth factor (NGF increased pain sensation and inhibited neural remodeling and lymphatic vessel regression processes during wound recovery. A complementary in vivo approach, the corneal micropocket assay, revealed that NGF-laden pellets stimulated lymphangiogenesis and increased protein levels of VEGF-C. Adult human dermal lymphatic endothelial cells did not express canonical NGF receptors TrkA and p75NTR or activate downstream MAPK- or Akt-pathway effectors in the presence of NGF, although NGF treatment increased their migratory and tubulogenesis capacities in vitro. Blockade of the VEGF-R2/R3 signaling pathway ablated NGF-mediated lymphangiogenesis in vivo. These findings suggest a hierarchical relationship with NGF functioning upstream of the VEGF family members, particularly VEGF-C, to stimulate lymphangiogenesis. Taken together, these studies show that NGF stimulates lymphangiogenesis and that NGF may act as a pathogenic factor that negatively regulates the normal neural and lymphatic vascular remodeling events that accompany wound recovery.

  18. A SURVEY OF RETINA BASED DISEASE IDENTIFICATION USING BLOOD VESSEL SEGMENTATION

    Directory of Open Access Journals (Sweden)

    P Kuppusamy

    2016-11-01

    Full Text Available The colour retinal photography is one of the most essential features to identify the confirmation of various eye diseases. The iris is primary attribute to authenticate the human. This research work presents the survey and comparison of various blood vessel related feature identification, segmentation, extraction and enhancement methods. Additionally, this study is observed the various databases performance for storing the images and testing in minimal time. This paper is also provides the better performance techniques based on the survey.

  19. Modeling the Role of the Glymphatic Pathway and Cerebral Blood Vessel Properties in Alzheimer's Disease Pathogenesis.

    Directory of Open Access Journals (Sweden)

    Christina Rose Kyrtsos

    Full Text Available Alzheimer's disease (AD is the most common cause of dementia in the elderly, affecting over 10% population over the age of 65 years. Clinically, AD is described by the symptom set of short term memory loss and cognitive decline, changes in mentation and behavior, and eventually long-term memory deficit as the disease progresses. On imaging studies, significant atrophy with subsequent increase in ventricular volume have been observed. Pathology on post-mortem brain specimens demonstrates the classic findings of increased beta amyloid (Aβ deposition and the presence of neurofibrillary tangles (NFTs within affected neurons. Neuroinflammation, dysregulation of blood-brain barrier transport and clearance, deposition of Aβ in cerebral blood vessels, vascular risk factors such as atherosclerosis and diabetes, and the presence of the apolipoprotein E4 allele have all been identified as playing possible roles in AD pathogenesis. Recent research has demonstrated the importance of the glymphatic system in the clearance of Aβ from the brain via the perivascular space surrounding cerebral blood vessels. Given the variety of hypotheses that have been proposed for AD pathogenesis, an interconnected, multilayer model offers a unique opportunity to combine these ideas into a single unifying model. Results of this model demonstrate the importance of vessel stiffness and heart rate in maintaining adequate clearance of Aβ from the brain.

  20. Semiautomated segmentation of blood vessels using ellipse-overlap criteria: Method and comparison to manual editing

    International Nuclear Information System (INIS)

    Shiffman, Smadar; Rubin, Geoffrey D.; Schraedley-Desmond, Pamela; Napel, Sandy

    2003-01-01

    Two-dimensional intensity-based methods for the segmentation of blood vessels from computed-tomography-angiography data often result in spurious segments that originate from other objects whose intensity distributions overlap with those of the vessels. When segmented images include spurious segments, additional methods are required to select segments that belong to the target vessels. We describe a method that allows experts to select vessel segments from sequences of segmented images with little effort. Our method uses ellipse-overlap criteria to differentiate between segments that belong to different objects and are separated in plane but are connected in the through-plane direction. To validate our method, we used it to extract vessel regions from volumes that were segmented via analysis of isolabel-contour maps, and showed that the difference between the results of our method and manually-edited results was within inter-expert variability. Although the total editing duration for our method, which included user-interaction and computer processing, exceeded that of manual editing, the extent of user interaction required for our method was about a fifth of that required for manual editing

  1. Effects of X-irradiation on artificial blood vessel wall degradation by invasive tumor cells

    International Nuclear Information System (INIS)

    Heisel, M.A.; Laug, W.E.; Stowe, S.M.; Jones, P.A.

    1984-01-01

    Artificial vessel wall cultures, constructed by growing arterial endothelial cells on preformed layers of rat smooth muscle cells, were used to evaluate the effects of X-irradiation on tumor cell-induced tissue degradation. Bovine endothelial cells had radiation sensitivities similar to those of rat smooth muscle cells. Preirradiation of smooth muscle cells, before the addition of human fibrosarcoma (HT 1080) cells, did not increase the rate of degradation and destruction by the invasive cells. However, the degradation rate was decreased if the cultures were irradiated after the addition of HT 1080 cells. The presence of bovine endothelial cells markedly inhibited the destructive abilities of fibrosarcoma cells, but preirradiation of artificial vessel walls substantially decreased their capabilities to resist HT 1080-induced lysis. These findings suggest that the abilities of blood vessels to limit extravasation may be compromised by ionizing radiation

  2. High Endothelial Venules and Other Blood Vessels: Critical Regulators of Lymphoid Organ Development and Function

    Science.gov (United States)

    Ager, Ann

    2017-01-01

    The blood vasculature regulates both the development and function of secondary lymphoid organs by providing a portal for entry of hemopoietic cells. During the development of lymphoid organs in the embryo, blood vessels deliver lymphoid tissue inducer cells that initiate and sustain the development of lymphoid tissues. In adults, the blood vessels are structurally distinct from those in other organs due to the requirement for high levels of lymphocyte recruitment under non-inflammatory conditions. In lymph nodes (LNs) and Peyer’s patches, high endothelial venules (HEVs) especially adapted for lymphocyte trafficking form a spatially organized network of blood vessels, which controls both the type of lymphocyte and the site of entry into lymphoid tissues. Uniquely, HEVs express vascular addressins that regulate lymphocyte entry into lymphoid organs and are, therefore, critical to the function of lymphoid organs. Recent studies have demonstrated important roles for CD11c+ dendritic cells in the induction, as well as the maintenance, of vascular addressin expression and, therefore, the function of HEVs. Tertiary lymphoid organs (TLOs) are HEV containing LN-like structures that develop inside organized tissues undergoing chronic immune-mediated inflammation. In autoimmune lesions, the development of TLOs is thought to exacerbate disease. In cancerous tissues, the development of HEVs and TLOs is associated with improved patient outcomes in several cancers. Therefore, it is important to understand what drives the development of HEVs and TLOs and how these structures contribute to pathology. In several human diseases and experimental animal models of chronic inflammation, there are some similarities between the development and function of HEVs within LN and TLOs. This review will summarize current knowledge of how hemopoietic cells with lymphoid tissue-inducing, HEV-inducing, and HEV-maintaining properties are recruited from the bloodstream to induce the development and

  3. High-resolution ultrasound imaging and noninvasive optoacoustic monitoring of blood variables in peripheral blood vessels

    Science.gov (United States)

    Petrov, Irene Y.; Petrov, Yuriy; Prough, Donald S.; Esenaliev, Rinat O.

    2011-03-01

    Ultrasound imaging is being widely used in clinics to obtain diagnostic information non-invasively and in real time. A high-resolution ultrasound imaging platform, Vevo (VisualSonics, Inc.) provides in vivo, real-time images with exceptional resolution (up to 30 microns) using high-frequency transducers (up to 80 MHz). Recently, we built optoacoustic systems for probing radial artery and peripheral veins that can be used for noninvasive monitoring of total hemoglobin concentration, oxyhemoglobin saturation, and concentration of important endogenous and exogenous chromophores (such as ICG). In this work we used the high-resolution ultrasound imaging system Vevo 770 for visualization of the radial artery and peripheral veins and acquired corresponding optoacoustic signals from them using the optoacoustic systems. Analysis of the optoacoustic data with a specially developed algorithm allowed for measurement of blood oxygenation in the blood vessels as well as for continuous, real-time monitoring of arterial and venous blood oxygenation. Our results indicate that: 1) the optoacoustic technique (unlike pure optical approaches and other noninvasive techniques) is capable of accurate peripheral venous oxygenation measurement; and 2) peripheral venous oxygenation is dependent on skin temperature and local hemodynamics. Moreover, we performed for the first time (to the best of our knowledge) a comparative study of optoacoustic arterial oximetry and a standard pulse oximeter in humans and demonstrated superior performance of the optoacoustic arterial oximeter, in particular at low blood flow.

  4. Patterns of left ventricular remodeling among patients with essential and secondary hypertension.

    Science.gov (United States)

    Radulescu, Dan; Stoicescu, Laurentiu; Buzdugan, Elena; Donca, Valer

    2013-12-01

    High blood pressure causes left ventricular hypertrophy, which is a negative prognostic factor among hypertensive patients. To assess left ventricular geometric remodeling patterns in patients with essential hypertension or with hypertension secondary to parenchymal renal disease. We analyzed data from echocardiograms performed in 250 patients with essential hypertension (150 females) and 100 patients with secondary hypertension (60 females). The interventricular septum and the left ventricular posterior wall thickness were measured in the parasternal long-axis. Left ventricular mass was calculated using the Devereaux formula. The most common remodeling type in females and males with essential hypertension were eccentric and concentric left ventricular hypertrophy (cLVH), respectively. Among patients with secondary arterial hypertension, cLVH was most commonly observed in both genders. The prevalence of left ventricular hypertrophy was higher among patients with secondary hypertension. The left ventricular mass index and the relative left ventricular wall thickness were higher in males and also in the secondary hypertension group. Age, blood pressure values and the duration of hypertension, influenced remodeling patterns. We documented a higher prevalence of LVH among patients with secondary hypertension. The type of ventricular remodeling depends on gender, age, type of hypertension, blood pressure values and the duration of hypertension.

  5. Photoacoustic imaging of blood vessels with a double-ring sensor featuring a narrow angular aperture

    NARCIS (Netherlands)

    Kolkman, R.G.M.; Hondebrink, Erwin; Steenbergen, Wiendelt; van Leeuwen, Ton; de Mul, F.F.M.

    2004-01-01

    A photoacoustic double-ring sensor, featuring a narrow angular aperture, is developed for laser-induced photoacoustic imaging of blood vessels. An integrated optical fiber enables reflection-mode detection of ultrasonic waves. By using the cross-correlation between the signals detected by the two

  6. Tumor blood vessel "normalization" improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer

    Energy Technology Data Exchange (ETDEWEB)

    D. W. Nigg

    2012-01-01

    We previously demonstrated the efficacy of BNCT mediated by boronophenylalanine (BPA) to treat tumors in a hamster cheek pouch model of oral cancer with no normal tissue radiotoxicity and moderate, albeit reversible, mucositis in precancerous tissue around treated tumors. It is known that boron targeting of the largest possible proportion of tumor cells contributes to the success of BNCT and that tumor blood vessel normalization improves drug delivery to the tumor. Within this context, the aim of the present study was to evaluate the effect of blood vessel normalization on the therapeutic efficacy and potential radiotoxicity of BNCT in the hamster cheek pouch model of oral cancer.

  7. Tumor blood vessel 'normalization' improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer

    International Nuclear Information System (INIS)

    Nigg, D.W.

    2012-01-01

    We previously demonstrated the efficacy of BNCT mediated by boronophenylalanine (BPA) to treat tumors in a hamster cheek pouch model of oral cancer with no normal tissue radiotoxicity and moderate, albeit reversible, mucositis in precancerous tissue around treated tumors. It is known that boron targeting of the largest possible proportion of tumor cells contributes to the success of BNCT and that tumor blood vessel normalization improves drug delivery to the tumor. Within this context, the aim of the present study was to evaluate the effect of blood vessel normalization on the therapeutic efficacy and potential radiotoxicity of BNCT in the hamster cheek pouch model of oral cancer.

  8. Quantitative phase imaging characterization of tumor-associated blood vessel formation on a chip

    Science.gov (United States)

    Guo, Peng; Huang, Jing; Moses, Marsha A.

    2018-02-01

    Angiogenesis, the formation of new blood vessels from existing ones, is a biological process that has an essential role in solid tumor growth, development, and progression. Recent advances in Lab-on-a-Chip technology has created an opportunity for scientists to observe endothelial cell (EC) behaviors during the dynamic process of angiogenesis using a simple and economical in vitro platform that recapitulates in vivo blood vessel formation. Here, we use quantitative phase imaging (QPI) microscopy to continuously and non-invasively characterize the dynamic process of tumor cell-induced angiogenic sprout formation on a microfluidic chip. The live tumor cell-induced angiogenic sprouts are generated by multicellular endothelial sprouting into 3 dimensional (3D) Matrigel using human umbilical vein endothelial cells (HUVECs). By using QPI, we quantitatively measure a panel of cellular morphological and behavioral parameters of each individual EC participating in this sprouting. In this proof-of-principle study, we demonstrate that QPI is a powerful tool that can provide real-time quantitative analysis of biological processes in in vitro 3D biomimetic devices, which, in turn, can improve our understanding of the biology underlying functional tissue engineering.

  9. Subsurface thermal behaviour of tissue mimics embedded with large blood vessels during plasmonic photo-thermal therapy.

    Science.gov (United States)

    Paul, Anup; Narasimhan, Arunn; Das, Sarit K; Sengupta, Soujit; Pradeep, Thalappil

    2016-11-01

    The purpose of this study was to understand the subsurface thermal behaviour of a tissue phantom embedded with large blood vessels (LBVs) when exposed to near-infrared (NIR) radiation. The effect of the addition of nanoparticles to irradiated tissue on the thermal sink behaviour of LBVs was also studied. Experiments were performed on a tissue phantom embedded with a simulated blood vessel of 2.2 mm outer diameter (OD)/1.6 mm inner diameter (ID) with a blood flow rate of 10 mL/min. Type I collagen from bovine tendon and agar gel were used as tissue. Two different nanoparticles, gold mesoflowers (AuMS) and graphene nanostructures, were synthesised and characterised. Energy equations incorporating a laser source term based on multiple scattering theories were solved using finite element-based commercial software. The rise in temperature upon NIR irradiation was seen to vary according to the position of the blood vessel and presence of nanoparticles. While the maximum rise in temperature was about 10 °C for bare tissue, it was 19 °C for tissue embedded with gold nanostructures and 38 °C for graphene-embedded tissues. The axial temperature distribution predicted by computational simulation matched the experimental observations. A different subsurface temperature distribution has been obtained for different tissue vascular network models. The position of LBVs must be known in order to achieve optimal tissue necrosis. The simulation described here helps in predicting subsurface temperature distributions within tissues during plasmonic photo-thermal therapy so that the risks of damage and complications associated with in vivo experiments and therapy may be avoided.

  10. Gamma-secretase inhibitor treatment promotes VEGF-A-driven blood vessel growth and vascular leakage but disrupts neovascular perfusion.

    Directory of Open Access Journals (Sweden)

    Mattias Kalén

    Full Text Available The Notch signaling pathway is essential for normal development due to its role in control of cell differentiation, proliferation and survival. It is also critically involved in tumorigenesis and cancer progression. A key enzyme in the activation of Notch signaling is the gamma-secretase protein complex and therefore, gamma-secretase inhibitors (GSIs--originally developed for Alzheimer's disease--are now being evaluated in clinical trials for human malignancies. It is also clear that Notch plays an important role in angiogenesis driven by Vascular Endothelial Growth Factor A (VEGF-A--a process instrumental for tumor growth and metastasis. The effect of GSIs on tumor vasculature has not been conclusively determined. Here we report that Compound X (CX, a GSI previously reported to potently inhibit Notch signaling in vitro and in vivo, promotes angiogenic sprouting in vitro and during developmental angiogenesis in mice. Furthermore, CX treatment suppresses tumor growth in a mouse model of renal carcinoma, leads to the formation of abnormal vessels and an increased tumor vascular density. Using a rabbit model of VEGF-A-driven angiogenesis in skeletal muscle, we demonstrate that CX treatment promotes abnormal blood vessel growth characterized by vessel occlusion, disrupted blood flow, and increased vascular leakage. Based on these findings, we propose a model for how GSIs and other Notch inhibitors disrupt tumor blood vessel perfusion, which might be useful for understanding this new class of anti-cancer agents.

  11. ICG-assisted blood vessel detection during stereotactic neurosurgery: simulation study on excitation power limitations due to thermal effects in human brain tissue.

    Science.gov (United States)

    Rühm, Adrian; Göbel, Werner; Sroka, Ronald; Stepp, Herbert

    2014-09-01

    Intraoperative blood vessel detection based on intraluminal indocyanin-green (ICG) would allow to minimize the risk of blood vessel perforation during stereotactic brain tumor biopsy. For a fiber-based approach compatible with clinical conditions, the maximum tolerable excitation light power was derived from simulations of the thermal heat load on the tissue. Using the simulation software LITCIT, the temperature distribution in human brain tissue was calculated as a function of time for realistic single-fiber probes (0.72mm active diameter, numerical aperture 0.35, optional focusing to 0.29mm diameter) and for the optimum ICG excitation wavelength of 785nm. The asymptotic maximum temperature in the simulated tissue region was derived for different radiant fluxes at the distal fiber end. Worst case values were assumed for all other parameters. In addition to homogeneous (normal and tumor) brain tissue with homogeneous blood perfusion, models with localized extra blood vessels incorporated ahead of the distal fiber end were investigated. If one demands that destruction of normal brain tissue must be excluded by limiting the tissue heating to 42°C, then the radiant flux at the distal fiber end must be limited to 33mW with and 43mW without focusing. When considering extra blood vessels of 0.1mm diameter incorporated into homogeneously perfused brain tissue, the tolerable radiant flux is reduced to 22mW with and 32mW without focusing. The threshold value according to legal laser safety regulations for human skin tissue is 28.5mW. For the envisaged modality of blood vessel detection, light power limits for an application-relevant fiber configuration were determined and found to be roughly consistent with present legal regulations for skin tissue. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. A composite chitosan-gelatin bi-layered, biomimetic macroporous scaffold for blood vessel tissue engineering.

    Science.gov (United States)

    Badhe, Ravindra V; Bijukumar, Divya; Chejara, Dharmesh R; Mabrouk, Mostafa; Choonara, Yahya E; Kumar, Pradeep; du Toit, Lisa C; Kondiah, Pierre P D; Pillay, Viness

    2017-02-10

    A composite chitosan-gelatin macroporous hydrogel-based scaffold with bi-layered tubular architecture was engineered by solvent casting-co-particulate leaching. The scaffold constituted an inner macroporous layer concealed by a non-porous outer layer mimicking the 3D matrix of blood vessels with cellular adhesion and proliferation. The scaffold was evaluated for its morphological, physicochemical, physicomechanical and biodurability properties employing SEM, FTIR, DSC, XRD, porositometry, rheology and texture analysis. The fluid uptake and biodegradation in the presence of lysozymes was also investigated. Cellular attachment and proliferation was analysed using human dermal fibroblasts (HDF-a) seeded onto the scaffold and evaluated by MTT assay, SEM, and confocal microscopy. Results demonstrated that the scaffold had a desirable tensile strength=95.81±11kPa, elongation at break 112.5±13%, porosity 82% and pores between 100 and 230μm, 50% in vitro biodegradation at day 16 and proliferated fibroblasts over 20 days. These results demonstrate that scaffold may be an excellent tubular archetype for blood vessel tissue engineering. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Modeling the Role of the Glymphatic Pathway and Cerebral Blood Vessel Properties in Alzheimer’s Disease Pathogenesis

    Science.gov (United States)

    Kyrtsos, Christina Rose; Baras, John S.

    2015-01-01

    Alzheimer’s disease (AD) is the most common cause of dementia in the elderly, affecting over 10% population over the age of 65 years. Clinically, AD is described by the symptom set of short term memory loss and cognitive decline, changes in mentation and behavior, and eventually long-term memory deficit as the disease progresses. On imaging studies, significant atrophy with subsequent increase in ventricular volume have been observed. Pathology on post-mortem brain specimens demonstrates the classic findings of increased beta amyloid (Aβ) deposition and the presence of neurofibrillary tangles (NFTs) within affected neurons. Neuroinflammation, dysregulation of blood-brain barrier transport and clearance, deposition of Aβ in cerebral blood vessels, vascular risk factors such as atherosclerosis and diabetes, and the presence of the apolipoprotein E4 allele have all been identified as playing possible roles in AD pathogenesis. Recent research has demonstrated the importance of the glymphatic system in the clearance of Aβ from the brain via the perivascular space surrounding cerebral blood vessels. Given the variety of hypotheses that have been proposed for AD pathogenesis, an interconnected, multilayer model offers a unique opportunity to combine these ideas into a single unifying model. Results of this model demonstrate the importance of vessel stiffness and heart rate in maintaining adequate clearance of Aβ from the brain. PMID:26448331

  14. Automatic blood vessel based-liver segmentation using the portal phase abdominal CT

    Science.gov (United States)

    Maklad, Ahmed S.; Matsuhiro, Mikio; Suzuki, Hidenobu; Kawata, Yoshiki; Niki, Noboru; Shimada, Mitsuo; Iinuma, Gen

    2018-02-01

    Liver segmentation is the basis for computer-based planning of hepatic surgical interventions. In diagnosis and analysis of hepatic diseases and surgery planning, automatic segmentation of liver has high importance. Blood vessel (BV) has showed high performance at liver segmentation. In our previous work, we developed a semi-automatic method that segments the liver through the portal phase abdominal CT images in two stages. First stage was interactive segmentation of abdominal blood vessels (ABVs) and subsequent classification into hepatic (HBVs) and non-hepatic (non-HBVs). This stage had 5 interactions that include selective threshold for bone segmentation, selecting two seed points for kidneys segmentation, selection of inferior vena cava (IVC) entrance for starting ABVs segmentation, identification of the portal vein (PV) entrance to the liver and the IVC-exit for classifying HBVs from other ABVs (non-HBVs). Second stage is automatic segmentation of the liver based on segmented ABVs as described in [4]. For full automation of our method we developed a method [5] that segments ABVs automatically tackling the first three interactions. In this paper, we propose full automation of classifying ABVs into HBVs and non- HBVs and consequently full automation of liver segmentation that we proposed in [4]. Results illustrate that the method is effective at segmentation of the liver through the portal abdominal CT images.

  15. Glucose metabolism in diabetic blood vessels

    International Nuclear Information System (INIS)

    Brown, B.J.; Crass, M.F. III

    1986-01-01

    Since glycolysis appears to be coupled to active ion transport in vascular smooth muscle, alterations in glucose metabolism may contribute to cellular dysfunction and angiopathy in diabetes. Uptake and utilization of glucose were studied in perfused blood vessels in which pulsatile flow and perfusion pressure were similar to those measured directly in vivo. Thoracic aortae isolated from 8-wk alloxan diabetic (D) and nondiabetic control rabbits were cannulated, tethered, and perfused with oxygenated buffer containing 7 or 25 mM glucose and tracer amounts of glucose-U -14 C. Norepinephrine (NE) (10 -6 M) and/or insulin (I) (150 μU/ml) and albumin (0.2%) were added. NE-induced tension development increased glucose uptake 39% and 14 CO 2 and lactate production 2.3-fold. With 7 mM glucose, marked decreases in glucose uptake (74%), 14 CO 2 (68%), lactate (30%), total tissue glycogen (75%), and tissue phospholipids (70%) were observed in D. Addition of I or elevation of exogenous glucose to 25 mM normalized glucose uptake, but had differential effects on the pattern of substrate utilization. Thus, in D, there was a marked depression of vascular glucose metabolism that was partially reversed by addition of low concentrations of insulin or D levels of glucose

  16. Rapid sealing and cutting of porcine blood vessels, ex vivo, using a high-power, 1470-nm diode laser.

    Science.gov (United States)

    Giglio, Nicholas C; Hutchens, Thomas C; Perkins, William C; Latimer, Cassandra; Ward, Arlen; Nau, William H; Fried, Nathaniel M

    2014-03-01

    Suture ligation with subsequent cutting of blood vessels to maintain hemostasis during surgery is time consuming and skill intensive. Energy-based electrosurgical and ultrasonic devices are often used to replace sutures and mechanical clips to provide rapid hemostasis and decrease surgery time. Some of these devices may create undesirably large collateral zones of thermal damage and tissue necrosis, or require separate mechanical blades for cutting. Infrared lasers are currently being explored as alternative energy sources for vessel sealing applications. In a previous study, a 1470-nm laser was used to seal vessels 1 to 6 mm in diameter in 5 s, yielding burst pressures of ∼500  mmHg. The purpose of this study was to provide vessel sealing times comparable with current energy-based devices, incorporate transection of sealed vessels, and demonstrate high vessel burst pressures to provide a safety margin for future clinical use. A 110-W, 1470-nm laser beam was transmitted through a fiber and beam shaping optics, producing a 90-W linear beam 3.0 by 9.5 mm for sealing (400  W/cm2), and 1.1 by 9.6 mm for cutting (1080  W/cm2). A two-step process sealed and then transected ex vivo porcine renal vessels (1.5 to 8.5 mm diameter) in a bench top setup. Seal and cut times were 1.0 s each. A burst pressure system measured seal strength, and histologic measurements of lateral thermal spread were also recorded. All blood vessels tested (n=55 seal samples) were sealed and cut, with total irradiation times of 2.0 s and mean burst pressures of 1305±783  mmHg. Additional unburst vessels were processed for histological analysis, showing a lateral thermal spread of 0.94±0.48  mm (n=14 seal samples). This study demonstrated that an optical-based system is capable of precisely sealing and cutting a wide range of porcine renal vessel sizes and, with further development, may provide an alternative to radiofrequency- and ultrasonic-based vessel sealing devices.

  17. Comparison between PVHIS on the MRI and the permeability of brain blood vessels in elderly patients

    International Nuclear Information System (INIS)

    Yamaguchi, Katsuhiko; Tanaka, Yuriko; Kubo, Hideki; Takagi, Yasushi; Tachikawa, Shinzo; Katsunuma, Hideyo.

    1989-01-01

    The degree of PVHIS (periventricular high intensity signal) on the MRI was composed with the permeability of brain blood vessels using the cerebrospinal fluid (CSF)/serum ratio for albumin, and the CSF/serum ratio for IgG in elderly patients. The 47 elderly patients (mean age=79.9) were divided into three groups: (1) Mild group (20 cases, M:6, F:14, mean age=75.8), (2) Moderate group (18 cases, M:7, F:11, mean age=82.6), (3) Severe group (9 cases, M:2, F:7, mean age=82.9), in accordance with the degree of PVHIS on the MRI. The MRI was operated at a field strength of 0.22 tesla. The pulse sequence (used on all patients) had a repetition times (TR) of 2,000 msec and a time to echo (TE) of 40 msec. The levels of albumin and IgG in the serum and CSF were measured. The CSF/serum ratio for albumin was used of analyze the permeability of the brain blood vessels in each group. There was no significant difference in the level of the serum albumin, the CSF albumin, the serum IgG, the CSF IgG and the CSF/serum ratio for IgG among the three groups. The same was found to be true for the IgG index which indicates the synthesis of immunoglobulin in the central nervous system. However, there was a statistically significant difference (p<0.05) in the CSF/serum ratio for albumin between groups (1) and (3). The increased CSF/serum ratio for albumin in the severe group indicated there were confluent lesions involving the entire extent of the periventriular white matter on the MRI. This suggested an increased permeability of brain blood vessels which revealed the dysfunction of the blood brain barrier due to affected cerebral endothelial cells in capillaries. (author)

  18. Hemodynamics in stenotic vessels of small diameter under steady state conditions: Effect of viscoelasticity and migration of red blood cells.

    Science.gov (United States)

    Dimakopoulos, Yannis; Kelesidis, George; Tsouka, Sophia; Georgiou, Georgios C; Tsamopoulos, John

    2015-01-01

    In microcirculation, the non-Newtonian behavior of blood and the complexity of the microvessel network are responsible for the high flow resistance and the large reduction of the blood pressure. Red blood cell aggregation along with inward radial migration are two significant mechanisms determining the former. Yet, their impact on hemodynamics in non-straight vessels is not well understood. In this study, the steady state blood flow in stenotic rigid vessels is examined, employing a sophisticated non-homogeneous constitutive law. The effect of red blood cells migration on the hydrodynamics is quantified and the constitutive model's accuracy is evaluated. A numerical algorithm based on the two-dimensional mixed finite element method and the EVSS/SUPG technique for a stable discretization of the mass and momentum conservation equations in addition to the constitutive model is employed. The numerical simulations show that a cell-depleted layer develops along the vessel wall with an almost constant thickness for slow flow conditions. This causes the reduction of the drag force and the increase of the pressure gradient as the constriction ratio decreases. Viscoelastic effects in blood flow were found to be responsible for steeper decreases of tube and discharge hematocrits as decreasing function of constriction ratio.

  19. The effects of Anadara granosa shell-Stichopus hermanni on bFGF expressions and blood vessel counts in the bone defect healing process of Wistar rats

    Directory of Open Access Journals (Sweden)

    Rima Parwati Sari

    2017-12-01

    Full Text Available Background: Bone damage can be caused by various factors with treatment usually involving graft materials being applied to the defective area. Moreover, in the bone defect healing process, blood vessels are also considered to be an important energy source for cell proliferation. One of the angiogenic factors playing an important role in blood vessel formation is basic fibroblast growth factor (bFGF. Furthermore, synthesized hydroxyapatite derived from Anadara granosa (AG shells constitutes one of the potential materials for use in bone graft. The gold sea cucumber genus Stichopus hermanni (SH possesses the ability to stimulate endothelial progenitor cells inducing bFGF. Purpose: This study aims to investigate the effects of AG shells and SH on bFGF expressions and blood vessel counts within the bone healing process. Methods: Twenty four male Wistar rats were divided into three groups, namely: a control group (C, a treatment group was administered with blood cockle shell (AG, and a treatment group with blood cockle shell and golden sea cucumber (AG+SH. Defects were made on their femurs measuring half the diameter of a circular, no. 018. bur These rats were subsequently sacrificed on day 7 after surgery. The expressions of bFGF were measured by means of IHC technique, while the number of blood vessels was quantified using HE technique. The resulting data was subjected to statistical analysis using an Anova test followed by an LSD test (p < 0.05. Results: The one-way Anova test results combined with those of an LSD test showed there to be significant differences in bFGF expressions and blood vessel counts between the control group (K and the treatment group (AG as well as between the treatment group (AG and the treatment group (AG+SH. Conclusions: A combination of Anadara granosa shell and Stichopus hermanni can increase the expression of bFGF and the number of blood vessels on day 7 during the bone healing process in Wistar rats.

  20. C-reactive protein and chitinase 3-like protein 1 as biomarkers of spatial redistribution of retinal blood vessels on digital retinal photography in patients with diabetic retinopathy.

    Science.gov (United States)

    Cekić, Sonja; Cvetković, Tatjana; Jovanović, Ivan; Jovanović, Predrag; Pesić, Milica; Stanković Babić, Gordana; Milenković, Svetislav; Risimić, Dijana

    2014-08-20

    The aim of the study was to investigate the correlation between the levels of C-reactive protein (CRP) and chitinase 3-like protein 1 (YKL-40) in blood samples with morpohometric parameters of retinal blood vessels in patients with diabetic retinopathy. Blood laboratory examination of 90 patients included the measurement of glycemia, HbA1C, total cholesterol, LDL-C, HDL-C, triglycerides and CRP. Levels of YKL-40 were detected and measured in serum by ELISA (Micro VueYKL-40 EIA Kit, Quidel Corporation, San Diego, USA). YKL-40 correlated positively with diameter and negatively with number of retinal blood vessels. The average number of the blood vessels per retinal zone was significantly higher in the group of patients with mild non-proliferative diabetic retinopathy than in the group with severe form in the optic disc and all five retinal zones. The average outer diameter of the evaluated retinal zones and optic disc vessels was significantly higher in the group with severe compared to the group with mild diabetic retinopathy. Morphological analysis of the retinal vessels on digital fundus photography and correlation with YKL-40 may be valuable for the follow-up of diabetic retinopathy.

  1. Effect of gender on training-induced vascular remodeling in SHR

    Directory of Open Access Journals (Sweden)

    S.L. Amaral

    2011-09-01

    Full Text Available There is accumulating evidence that physical inactivity, associated with the modern sedentary lifestyle, is a major determinant of hypertension. It represents the most important modifiable risk factor for cardiovascular diseases, which are the leading cause of morbidity and mortality for both men and women. In addition to involving sympathetic overactivity that alters hemodynamic parameters, hypertension is accompanied by several abnormalities in the skeletal muscle circulation including vessel rarefaction and increased arteriole wall-to-lumen ratio, which contribute to increased total peripheral resistance. Low-intensity aerobic training is a promising tool for the prevention, treatment and control of high blood pressure, but its efficacy may differ between men and women and between male and female animals. This review focuses on peripheral training-induced adaptations that contribute to a blood pressure-lowering effect, with special attention to differential responses in male and female spontaneously hypertensive rats (SHR. Heart, diaphragm and skeletal muscle arterioles (but not kidney arterioles undergo eutrophic outward remodeling in trained male SHR, which contributed to a reduction of peripheral resistance and to a pressure fall. In contrast, trained female SHR showed no change in arteriole wall-to-lumen ratio and no pressure fall. On the other hand, training-induced adaptive changes in capillaries and venules (increased density were similar in male and female SHR, supporting a similar hyperemic response to exercise.

  2. Effect of gender on training-induced vascular remodeling in SHR.

    Science.gov (United States)

    Amaral, S L; Michelini, L C

    2011-09-01

    There is accumulating evidence that physical inactivity, associated with the modern sedentary lifestyle, is a major determinant of hypertension. It represents the most important modifiable risk factor for cardiovascular diseases, which are the leading cause of morbidity and mortality for both men and women. In addition to involving sympathetic overactivity that alters hemodynamic parameters, hypertension is accompanied by several abnormalities in the skeletal muscle circulation including vessel rarefaction and increased arteriole wall-to-lumen ratio, which contribute to increased total peripheral resistance. Low-intensity aerobic training is a promising tool for the prevention, treatment and control of high blood pressure, but its efficacy may differ between men and women and between male and female animals. This review focuses on peripheral training-induced adaptations that contribute to a blood pressure-lowering effect, with special attention to differential responses in male and female spontaneously hypertensive rats (SHR). Heart, diaphragm and skeletal muscle arterioles (but not kidney arterioles) undergo eutrophic outward remodeling in trained male SHR, which contributed to a reduction of peripheral resistance and to a pressure fall. In contrast, trained female SHR showed no change in arteriole wall-to-lumen ratio and no pressure fall. On the other hand, training-induced adaptive changes in capillaries and venules (increased density) were similar in male and female SHR, supporting a similar hyperemic response to exercise.

  3. Development of PIE techniques for irradiated LWR pressure vessel steels

    International Nuclear Information System (INIS)

    Nishi, Masahiro; Kizaki, Minoru; Sukegawa, Tomohide

    1999-01-01

    For the evaluation of safety and integrity of light water reactors (LWRs), various post irradiation examinations (PIEs) of reactor pressure vessel (RPV) steels and fuel claddings have been carried out in the Research Hot Laboratory (RHL). In recent years, the instrumented Charpy impact testing machine was remodeled aiming at the improvement of accuracy and reliability. By this remodeling, absorbed energy and other useful information on impact properties can be delivered from the force-displacement curve for the evaluation of neutron irradiation embrittlement behavior of LWR-RPV steels at one-time striking. In addition, two advanced PIE technologies are now under development. One is the remote machining of mechanical test pieces from actual irradiated pressure vessel steels. The other is development of low-cycle and high-cycle fatigue test technology in order to clarify the post-irradiation fatigue characteristics of structural and fuel cladding materials. (author)

  4. C - reactive protein and chitinase 3-like protein 1 as biomarkers of spatial redistribution of retinal blood vessels on digital retinal photography in patients with diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    Sonja Predrag Cekic

    2014-08-01

    Full Text Available The aim of the study was to investegate the correlation between the levels of CRP and YKL-40 in blood samples with morphometric parameters of retinal blood vessels in patients with diabetic retinopathy.Blood laboratory examination of 90 patients included the measurement of glycemia, HbA1C, total cholesterol, LDL-C, HDL-C, triglycerides and CRP. Levels of YKL-40 were detected and measured in serum by ELISA (Micro VueYKL-40 EIA Kit, Quidel Corporation, San Diego, USA.Morphmetric analysis was performed with ImageJ software (http://rsbweb.nih.gov/ij/ for digital retinal photography. We measured the number, diameter of retinal blood vessels in five different parts concentric to the optic disc. Differences between the morphometric parameters and the blood test analysis results were evaluated using the Student’s t – test. One Way ANOVA was used to establish the significance of differences.CRP and YKL-40 levels were moderately higher in the group of patients with severe diabetic retinopathy. Levels of YKL-40 correlated positively with diameter and negatively with number of retinal blood vessels. The average number of the blood vessels per retinal zone was significantly higher in the group of patients with mild non-proliferative diabetic retinopathy than in the group with severe form in the optic disc and all five retinal zones. The average outer diameter of the evaluated retinal zones and optic disc vessels was significantly higher in the group with severe compared to the group with mild diabetic retinopathy.Morphological analysis of the retinal vessels on digital fundus photography and correlation with YKL-40 may be valuable for the follow-up of diabetic retinopathy.

  5. The wall traction induced by flowing red blood cells in model microvessels and its potential mechanotransduction

    Science.gov (United States)

    Freund, Jonathan; Vermot, Julien

    2013-11-01

    There is evidence in early embryonic development, even well before advective oxygen transport is important, that the presence of red bloods cells per se trigger essential steps of normal vascular development. For example, showed that sequestration of blood cells early in the development of a mouse, such that the hematocrit is reduced, suppresses normal vascular network development. Vascular development also provides a model for remodeling and angiogenesis. We consider the transient stresses associated with blood cells flowing in model microvessels of comparable diameter to those at early stages of development (6 μm to 12 μm). A detailed simulation tool is used to show that passing blood cells present a significant fluctuating traction signature on the vessel wall, well above the mean stresses. This is particularly pronounced for slow flows (layer is also considered. NSF supported.

  6. Effect of heat transfer on unsteady MHD flow of blood in a permeable vessel in the presence of non-uniform heat source

    OpenAIRE

    A. Sinha; J.C. Misra; G.C. Shit

    2016-01-01

    This paper presents a theoretical analysis of blood flow and heat transfer in a permeable vessel in the presence of an external magnetic field. The unsteadiness in the coupled flow and temperature fields is considered to be caused due to the time-dependent stretching velocity and the surface temperature of the vessel. The non-uniform heat source/sink effect on blood flow and heat transfer is taken into account. This study is of potential value in the clinical treatment of cardiovascular disor...

  7. Unique identification code for medical fundus images using blood vessel pattern for tele-ophthalmology applications.

    Science.gov (United States)

    Singh, Anushikha; Dutta, Malay Kishore; Sharma, Dilip Kumar

    2016-10-01

    Identification of fundus images during transmission and storage in database for tele-ophthalmology applications is an important issue in modern era. The proposed work presents a novel accurate method for generation of unique identification code for identification of fundus images for tele-ophthalmology applications and storage in databases. Unlike existing methods of steganography and watermarking, this method does not tamper the medical image as nothing is embedded in this approach and there is no loss of medical information. Strategic combination of unique blood vessel pattern and patient ID is considered for generation of unique identification code for the digital fundus images. Segmented blood vessel pattern near the optic disc is strategically combined with patient ID for generation of a unique identification code for the image. The proposed method of medical image identification is tested on the publically available DRIVE and MESSIDOR database of fundus image and results are encouraging. Experimental results indicate the uniqueness of identification code and lossless recovery of patient identity from unique identification code for integrity verification of fundus images. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Intradialytic Hypotension and Cardiac Remodeling: A Vicious Cycle

    Directory of Open Access Journals (Sweden)

    Chia-Ter Chao

    2015-01-01

    Full Text Available Hemodynamic instability during hemodialysis is a common but often underestimated issue in the nephrologist practice. Intradialytic hypotension, namely, a decrease of systolic or mean blood pressure to a certain level, prohibits the safe and smooth achievement of ultrafiltration and solute removal goal in chronic dialysis patients. Studies have elucidated the potential mechanisms involved in the development of Intradialytic hypotension, including excessive ultrafiltration and loss of compensatory mechanisms for blood pressure maintenance. Cardiac remodeling could also be one important piece of the puzzle. In this review, we intend to discuss the role of cardiac remodeling, including left ventricular hypertrophy, in the development of Intradialytic hypotension. In addition, we will also provide evidence that a bidirectional relationship might exist between Intradialytic hypotension and left ventricular hypertrophy in chronic dialysis patients. A more complete understanding of the complex interactions in between could assist the readers in formulating potential solutions for the reduction of both phenomena.

  9. Endothelial Proliferation and Increased Blood - Brain Barrier Permeability in the Basal Ganglia in a Rat Model of 3,4-Dihydrozyphenyl-L-Alanine-Induced Dyskinesia

    DEFF Research Database (Denmark)

    Westin, Jenny E.; Lindgren, Hanna S.; Gardi, Jonathan Eyal

    2006-01-01

    3,4-Dihydroxyphenyl-L-alanine (L-DOPA)-induced dyskinesia is associated with molecular and synaptic plasticity in the basal ganglia, but the occurrence of structural remodeling through cell genesis has not been explored. In this study, rats with 6-hydroxydopamine lesions received injections of th...... of angiogenesis and blood-brain barrier dysfunction in an experimental model of L-DOPA-induced dyskinesia. These microvascular changes are likely to affect the kinetics of L-DOPA entry into the brain, favoring the occurrence of motor complications....... dyskinesia. The vast majority (60-80%) of the newborn cells stained positively for endothelial markers. This endothelial proliferation was associated with an upregulation of immature endothelial markers (nestin) and a downregulation of endothelial barrier antigen on blood vessel walls. In addition......, dyskinetic rats exhibited a significant increase in total blood vessel length and a visible extravasation of serum albumin in the two structures in which endothelial proliferation was most pronounced (substantia nigra pars reticulata and entopeduncular nucleus). The present study provides the first evidence...

  10. Tests of the geometrical description of blood vessels in a thermal model using counter-current geometries

    NARCIS (Netherlands)

    van Leeuwen, G. M.; Kotte, A. N.; Crezee, J.; Lagendijk, J. J.

    1997-01-01

    We have developed a thermal model, for use in hyperthermia treatment planning, in which blood vessels are described as geometrical objects; 3D curves with associated diameters. For the calculation of the heat exchange with the tissue an analytic result is used. To arrive at this result some

  11. An agent-based model of the response to angioplasty and bare-metal stent deployment in an atherosclerotic blood vessel.

    Directory of Open Access Journals (Sweden)

    Antonia E Curtin

    Full Text Available PURPOSE: While animal models are widely used to investigate the development of restenosis in blood vessels following an intervention, computational models offer another means for investigating this phenomenon. A computational model of the response of a treated vessel would allow investigators to assess the effects of altering certain vessel- and stent-related variables. The authors aimed to develop a novel computational model of restenosis development following an angioplasty and bare-metal stent implantation in an atherosclerotic vessel using agent-based modeling techniques. The presented model is intended to demonstrate the body's response to the intervention and to explore how different vessel geometries or stent arrangements may affect restenosis development. METHODS: The model was created on a two-dimensional grid space. It utilizes the post-procedural vessel lumen diameter and stent information as its input parameters. The simulation starting point of the model is an atherosclerotic vessel after an angioplasty and stent implantation procedure. The model subsequently generates the final lumen diameter, percent change in lumen cross-sectional area, time to lumen diameter stabilization, and local concentrations of inflammatory cytokines upon simulation completion. Simulation results were directly compared with the results from serial imaging studies and cytokine levels studies in atherosclerotic patients from the relevant literature. RESULTS: The final lumen diameter results were all within one standard deviation of the mean lumen diameters reported in the comparison studies. The overlapping-stent simulations yielded results that matched published trends. The cytokine levels remained within the range of physiological levels throughout the simulations. CONCLUSION: We developed a novel computational model that successfully simulated the development of restenosis in a blood vessel following an angioplasty and bare-metal stent deployment based on

  12. Nonparenchymal cells cultivated from explants of fibrotic liver resemble endothelial and smooth muscle cells from blood vessel walls

    International Nuclear Information System (INIS)

    Voss, B.; Rauterberg, J.; Pott, G.; Brehmer, U.; Allam, S.; Lehmann, R.; von Bassewitz, D.B.

    1982-01-01

    Tissue specimens from human fibrotic liver obtained by needle biopsy were cultured. Two cell types emerged from the tissue explants. From their morphology and biosynthetic products they resembled smooth muscle cells and endothelial cells from blood vessel walls. In the endothelial cells, factor VIII-associated protein was demonstrated by indirect immunofluorescence. Synthesis of collagen types I and III, basement membrane collagen types IV and V, and fibronectin by both cell types was observed by immunofluorescence microscopy. Homogeneous cultures of smooth muscle cells were observed in subcultures. After incubation with [ 14 C]glycine, collagen was isolated and characterized by CM cellulose chromatography, and consisted mainly of types I and III. These data suggest involvement of mesenchymal cells in hepatic fibrosis; they presumably originate from blood vessel or sinusoidal walls

  13. Effects of x rays on the morphology and physiology of the CNS blood vessels of mice

    Energy Technology Data Exchange (ETDEWEB)

    Gladysz, J [Akademia Medyczna, Poznan (Poland)

    1974-01-01

    Irradiation of the CNS of mice with 4000 to 7600 R produces transitional disorder of the permeability of vascular walls, followed by a permanent (irreversible) degenerative lesion of blood capillaries and the surrounding astrogial cells. Intensity of this alterations may however not be the same in different terminal blood vessels. It is very likely that the above described lesion appearing in the acute phase can be the main cause of further alterations in the CNS which are observed in late phase of postradiation disease.

  14. Blood Vessel Enhancement and Segmentation for Screening of Diabetic Retinopathy

    Directory of Open Access Journals (Sweden)

    Ibaa Jamal

    2012-06-01

    Full Text Available Diabetic retinopathy is an eye disease caused by the increase of insulin in blood and it is one of the main cuases of blindness in idusterlized countries. It is a progressive disease and needs an early detection and treatment. Vascular pattern of human retina helps the ophthalmologists in automated screening and diagnosis of diabetic retinopathy. In this article, we present a method for vascular pattern ehnacement and segmentation. We present an automated system which uses wavelets to enhance the vascular pattern and then it applies a piecewise threshold probing and adaptive thresholding for vessel localization and segmentation respectively. The method is evaluated and tested using publicly available retinal databases and we further compare our method with already proposed techniques.

  15. Blood vessels segmentation of hatching eggs based on fully convolutional networks

    Science.gov (United States)

    Geng, Lei; Qiu, Ling; Wu, Jun; Xiao, Zhitao

    2018-04-01

    FCN, trained end-to-end, pixels-to-pixels, predict result of each pixel. It has been widely used for semantic segmentation. In order to realize the blood vessels segmentation of hatching eggs, a method based on FCN is proposed in this paper. The training datasets are composed of patches extracted from very few images to augment data. The network combines with lower layer and deconvolution to enables precise segmentation. The proposed method frees from the problem that training deep networks need large scale samples. Experimental results on hatching eggs demonstrate that this method can yield more accurate segmentation outputs than previous researches. It provides a convenient reference for fertility detection subsequently.

  16. An Original Approach for Quantification of Blood Vessels on the Whole Tumour Section

    Directory of Open Access Journals (Sweden)

    Nga Tran Kim

    2003-01-01

    Full Text Available Relative abundance of tumour angiogenesis has been shown to be of clinical relevance in cancers of various locations such as the ovary. Nevertheless, several problems are encountered when quantifying tumour microvessels: (i as many other tumour markers, vascularity pattern is often heterogeneous within the tumour mass and even within the same histological section. As a consequence, an adequate acquisition method must be developed for accurate field sampling. (ii Manual microvessel counting is long, tedious and subject to poor reproducibility. Introduction in routine practice requires a fast, reproducible and reliable automatic image processing. In this study we present an original procedure combining a slide scanner image acquisition and a fully automatic image analysis sequence. The slide scanner offers the advantage of recording an image of the whole histological section for subsequent automatic blood vessel detection and hot spot area location. Microvessel density and surface fraction were measured for the whole section as well as within hot spots. Different immunostaining methods were tested in order to optimise the procedure. Moreover, the method proposed was submitted to a quality control procedure, with reference to interactive identification of microvessels at scanner level. This experiment showed that 93 to 97% of blood vessels were detected, according to the staining protocol used. Colour figures can be viewed on http://www.esacp.org/acp/2003/25‐2/kim.htm.

  17. Ablation of EIF5A2 induces tumor vasculature remodeling and improves tumor response to chemotherapy via regulation of matrix metalloproteinase 2 expression.

    Science.gov (United States)

    Wang, Feng-Wei; Cai, Mu-Yan; Mai, Shi-Juan; Chen, Jie-Wei; Bai, Hai-Yan; Li, Yan; Liao, Yi-Ji; Li, Chang-Peng; Tian, Xiao-Peng; Kung, Hsiang-Fu; Guan, Xin-Yuan; Xie, Dan

    2014-08-30

    Hepatocellular carcinoma (HCC) is a highly vascularized tumor with poor clinical outcome. Our previous work has shown that eukaryotic initiation factor 5A2 (EIF5A2) over-expression enhances HCC cell metastasis. In this study, EIF5A2 was identified to be an independent risk factor for poor disease-specific survival among HCC patients. Both in vitro and in vivo assays indicated that ablation of endogenous EIF5A2 inhibited tumor angiogenesis by reducing matrix metalloproteinase 2 (MMP-2) expression. Given that MMP-2 degrades collagen IV, a main component of the vascular basement membrane (BM), we subsequently investigated the effect of EIF5A2 on tumor vasculature remodeling using complementary approaches, including fluorescent immunostaining, transmission electron microscopy, tumor perfusion assays and tumor hypoxia assays. Taken together, our results indicate that EIF5A2 silencing increases tumor vessel wall continuity, increases blood perfusion and improves tumor oxygenation. Additionally, we found that ablation of EIF5A2 enhanced the chemosensitivity of HCC cells to 5-Fluorouracil (5-FU). Finally, we demonstrated that EIF5A2 might exert these functions by enhancing MMP-2 activity via activation of p38 MAPK and JNK/c-Jun pathways. This study highlights an important role of EIF5A2 in HCC tumor vessel remodeling and indicates that EIF5A2 represents a potential therapeutic target in the treatment of HCC.

  18. Morphological evaluation of the cerebral blood vessels in the late gestation fetal sheep following hypoxia in utero.

    Science.gov (United States)

    Baburamani, Ana A; Lo, Camden; Castillo-Melendez, Margie; Walker, David W

    2013-01-01

    Hypoxia can significantly contribute to the development of permanent brain injury in the term neonate; however the response of cerebral blood vessels is not well understood. This study aimed to quantitatively measure vascular density and morphology using laminin immunohistochemistry as a marker of blood vessels, and determine the effects of a single, severe bout of hypoxia (umbilical cord occlusion, UCO) late in gestation on the developing cerebrovasculature in fetal sheep. At 124-126 days gestation singleton fetal sheep underwent surgery for implantation of catheters and placement of an inflatable cuff around the umbilical cord. A 10 min UCO or sham UCO (n=5) occurred at 132 days gestation. Fetal brains were collected at 24 h (n=5) or 48 h (n=4) after UCO for vascular density and morphology analysis of laminin immunohistochemistry. 48 h following a single, brief bout of severe hypoxia late in gestation decreased vascular density was seen in the caudate nucleus and no changes in vascular morphology occurred. However closer analysis revealed a significant shift in the frequency of smaller (≤10 μm) to larger (≤100 μm) perimeter blood vessels in periventricular and subcortical white matter. Close examination of the frequency distribution of vascular perimeter highlights that alterations in vascular morphology persist in the near term fetal brain for up to 48 h following a brief (10 min) hypoxia in white but not gray matter. These findings suggest that the near term brain may still be vulnerable to white matter injury following in utero hypoxia. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Disrupting established tumor blood vessels: an emerging therapeutic strategy for cancer.

    Science.gov (United States)

    McKeage, Mark J; Baguley, Bruce C

    2010-04-15

    The unique characteristics of tumor vasculature represent an attractive target that may be exploited by vascular-targeting anticancer agents. A promising strategy involves the selective disruption of established tumor blood vessels by tumor-vascular disrupting agents (tumor-VDAs), which exhibit antivascular activity, resulting in inhibition of tumor blood flow and extensive necrosis within the tumor core. The tumor-VDA class can be subdivided into flavonoid compounds, which are related to flavone acetic acid, and tubulin-binding compounds. ASA404, of the flavonoid class, is the most advanced tumor-VDA in clinical development and has been evaluated preclinically and in several phase 1 and phase 2 studies. Preclinical studies have demonstrated the selective apoptosis of tumor endothelial cells and the inhibition of tumor blood flow. Synergistic activity was observed with ASA404 and with several chemotherapeutic agents, particularly taxanes. In clinical trials, compared with chemotherapy alone, ASA404 was tolerated well and produced improved activity in patients with nonsmall cell lung cancer when combined with paclitaxel and carboplatin. Phase 3 clinical trials are ongoing. Selectively targeting established tumor vasculature with tumor-VDAs represents a promising and innovative approach to improving the efficacy of standard anticancer therapies. (c) 2010 American Cancer Society.

  20. Study of blood flow inside the stenosis vessel under the effect of solenoid magnetic field using ferrohydrodynamics principles

    Science.gov (United States)

    Badfar, Homayoun; Motlagh, Saber Yekani; Sharifi, Abbas

    2017-10-01

    In this paper, biomagnetic blood flow in the stenosis vessel under the effect of the solenoid magnetic field is studied using the ferrohydrodynamics (FHD) model. The parabolic profile is considered at an inlet of the axisymmetric stenosis vessel. Blood is modeled as electrically non-conducting, Newtonian and homogeneous fluid. Finite volume and the SIMPLE (Semi-Implicit Method for Pressure Linked Equations) algorithm are utilized to discretize governing equations. The investigation is studied at different magnetic numbers ( MnF=164, 328, 1640 and 3280) and the number of the coil loops (three, five and nine loops). Results indicate an increase in heat transfer, wall shear stress and energy loss (pressure drop) with an increment in the magnetic number (ratio of Kelvin force to dynamic pressure force), arising from the FHD, and the number of solenoid loops. Furthermore, the flow pattern is affected by the magnetic field, and the temperature of blood can be decreased up to 1.48 {}°C under the effect of the solenoid magnetic field with nine loops and reference magnetic field ( B0) of 2 tesla.

  1. Evidence of Flicker-Induced Functional Hyperaemia in the Smallest Vessels of the Human Retinal Blood Supply.

    Directory of Open Access Journals (Sweden)

    Angelina Duan

    Full Text Available Regional changes in blood flow are initiated within neural tissue to help fuel local differences in neural activity. Classically, this response was thought to arise only in larger arterioles and venules. However, recently, it has been proposed that a the smallest vessels of the circulation make a comparable contribution, and b the response should be localised intermittently along such vessels, due to the known distribution of contractile mural cells. To assess these hypotheses in human neural tissue in vivo, we imaged the retinal microvasculature (diameters 3-28 μm non-invasively, using adaptive optics, before and after delivery of focal (360 μm patches of flickering visible light. Our results demonstrated a definite average response in 35% of all vessel segments analysed. In these responding vessels, the magnitude of proportional dilation (mean ± SEM for pre-capillary arterioles 13 ± 5%, capillaries 31 ± 8%, and post-capillary venules 10 ± 3% is generally far greater than the magnitudes we and others have measured in the larger retinal vessels, supporting proposition a above. The dilations observed in venules were unexpected based on previous animal work, and may be attributed either to differences in stimulus or species. Response heterogeneity across the network was high; responses were also heterogeneous along individual vessels (45% of vessel segments showed demonstrable locality in their response. These observations support proposition b above. We also observed a definite average constriction across 7% of vessel segments (mean ± SEM constriction for capillaries -16 ± 3.2%, and post-capillary venules -18 ± 12%, which paints a picture of dynamic redistribution of flow throughout the smallest vessel networks in the retina in response to local, stimulus-driven metabolic demand.

  2. Involvement of Inflammation and Adverse Vascular Remodelling in the Blood Pressure Raising Effect of Repeatedly Heated Palm Oil in Rats

    Directory of Open Access Journals (Sweden)

    Chun-Yi Ng

    2012-01-01

    Full Text Available Oil thermoxidation during deep frying generates harmful oxidative free radicals that induce inflammation and increase the risk of hypertension. This study aimed to investigate the effect of repeatedly heated palm oil on blood pressure, aortic morphometry, and vascular cell adhesion molecule-1 (VCAM-1 expression in rats. Male Sprague-Dawley rats were divided into five groups: control, fresh palm oil (FPO, one-time-heated palm oil (1HPO, five-time-heated palm oil (5HPO, or ten-time-heated palm oil (10HPO. Feeding duration was six months. Blood pressure was measured at baseline and monthly using tail-cuff method. After six months, the rats were sacrificed and the aortic arches were dissected for morphometric and immunohistochemical analyses. FPO group showed significantly lower blood pressure than all other groups. Blood pressure was increased significantly in 5HPO and 10HPO groups. The aortae of 5HPO and 10HPO groups showed significantly increased thickness and area of intima-media, circumferential wall tension, and VCAM-1 than other groups. Elastic lamellae were disorganised and fragmented in 5HPO- and 10HPO-treated rats. VCAM-1 expression showed a significant positive correlation with blood pressure. In conclusion, prolonged consumption of repeatedly heated palm oil causes blood pressure elevation, adverse remodelling, and increased VCAM-1, which suggests a possible involvement of inflammation.

  3. An automated vessel segmentation of retinal images using multiscale vesselness

    International Nuclear Information System (INIS)

    Ben Abdallah, M.; Malek, J.; Tourki, R.; Krissian, K.

    2011-01-01

    The ocular fundus image can provide information on pathological changes caused by local ocular diseases and early signs of certain systemic diseases, such as diabetes and hypertension. Automated analysis and interpretation of fundus images has become a necessary and important diagnostic procedure in ophthalmology. The extraction of blood vessels from retinal images is an important and challenging task in medical analysis and diagnosis. In this paper, we introduce an implementation of the anisotropic diffusion which allows reducing the noise and better preserving small structures like vessels in 2D images. A vessel detection filter, based on a multi-scale vesselness function, is then applied to enhance vascular structures.

  4. Intima-media thickness remodelling in hypertensive subjects with long-term well-controlled blood pressure levels.

    Science.gov (United States)

    Puato, Massimo; Boschetti, Giovanni; Rattazzi, Marcello; Zanon, Marta; Pesavento, Raffaele; Faggin, Elisabetta; Fania, Claudio; Benetti, Elisabetta; Palatini, Paolo; Pauletto, Paolo

    2017-02-01

    Aim of this study was to evaluate in a long follow-up the carotid artery remodelling in a cohort of young hypertensive subjects having good blood pressure (BP) control. We studied 20 grade I hypertensives (HT) by assessing the B-mode ultrasound of mean carotid intima-media thickness (mean-IMT) and maximum IMT (M-MAX) in each carotid artery segment (common, bulb, internal), bilaterally. We compared their ultrasound measurements with those recorded 5 and 10 years earlier. While the first 5-year follow-up was observational, in the second 5-year follow-up, lifestyle modifications and/or pharmacological therapy were started to obtain well-controlled BP levels. Office BP was measured at the time of the ultrasound studies and every 6 months during the follow-up. BP levels were: 10 years 144/91 mmHg, 5 years 143/90 mmHg and 129 ± 79 mmHg at the time of the study. In the first 5-year observational follow-up, both mean-IMT and M-MAX increased (Δ 0.116 and Δ 0.165 mm, respectively, p < 0.0005). In the 5-year intervention follow-up, characterized by well-controlled BP, mean-IMT slightly but significantly increased (Δ 0.084 mm, p = 0.004), whereas M-MAX remained stable (Δ 0.026 mm). In our HT, well-controlled BP levels were able to prevent pro-atherogenic remodelling (expressed by M-MAX). Conversely, good BP control slightly decreased but did not stop the progression in mean-IMT, which is likely to reflect some hypertrophy of the arterial media layer.

  5. Distribution of Vascular Patterns in Different Subtypes of Renal Cell Carcinoma. A Morphometric Study in Two Distinct Types of Blood Vessels.

    Science.gov (United States)

    Ruiz-Saurí, Amparo; García-Bustos, V; Granero, E; Cuesta, S; Sales, M A; Marcos, V; Llombart-Bosch, A

    2017-07-01

    To analyze the presence of mature and immature vessels as a prognostic factor in patients with renal cell carcinoma and propose a classification of renal cancer tumor blood vessels according to morphometric parameters. Tissue samples were obtained from 121 renal cell carcinoma patients who underwent radical nephrectomy. Staining with CD31 and CD34 was used to differentiate between immature (CD31+) and mature (CD34+) blood vessels. We quantified the microvascular density, microvascular area and different morphometric parameters: maximum diameter, minimum diameter, major axis, minor axis, perimeter, radius ratio and roundness. We found that the microvascular density was higher in CD31+ than CD34+ vessels, but CD34+ vessels were larger than CD31+ vessels, as well as being strongly correlated with the ISUP tumor grade. We also identified four vascular patterns: pseudoacinar, fascicular, reticular and diffuse. Pseudoacinar and fascicular patterns were more frequent in clear cell renal cell carcinoma (37.62 and 35.64% respectively), followed by reticular pattern (21.78%), while in chromophobe tumors the reticular pattern predominated (90%). The isolated pattern was present in all papillary tumors (100%). In healthy renal tissue, the pseudoacinar and isolated patterns were differentially found in the renal cortex and medulla respectively. We defined four distinct vascular patterns significantly related with the ISUP tumor grade in renal cell carcinomas. Further studies in larger series are needed in order to validate these results. Analysis of both mature and immature vessels (CD34+ and CD31+) provides additional information when evaluating microvascular density.

  6. Blood Pressure Control in Aging Predicts Cerebral Atrophy Related to Small-Vessel White Matter Lesions

    Directory of Open Access Journals (Sweden)

    Kyle C. Kern

    2017-05-01

    Full Text Available Cerebral small-vessel damage manifests as white matter hyperintensities and cerebral atrophy on brain MRI and is associated with aging, cognitive decline and dementia. We sought to examine the interrelationship of these imaging biomarkers and the influence of hypertension in older individuals. We used a multivariate spatial covariance neuroimaging technique to localize the effects of white matter lesion load on regional gray matter volume and assessed the role of blood pressure control, age and education on this relationship. Using a case-control design matching for age, gender, and educational attainment we selected 64 participants with normal blood pressure, controlled hypertension or uncontrolled hypertension from the Northern Manhattan Study cohort. We applied gray matter voxel-based morphometry with the scaled subprofile model to (1 identify regional covariance patterns of gray matter volume differences associated with white matter lesion load, (2 compare this relationship across blood pressure groups, and (3 relate it to cognitive performance. In this group of participants aged 60–86 years, we identified a pattern of reduced gray matter volume associated with white matter lesion load in bilateral temporal-parietal regions with relative preservation of volume in the basal forebrain, thalami and cingulate cortex. This pattern was expressed most in the uncontrolled hypertension group and least in the normotensives, but was also more evident in older and more educated individuals. Expression of this pattern was associated with worse performance in executive function and memory. In summary, white matter lesions from small-vessel disease are associated with a regional pattern of gray matter atrophy that is mitigated by blood pressure control, exacerbated by aging, and associated with cognitive performance.

  7. Changes in peripapillary blood vessel density in Graves' orbitopathy after orbital decompression surgery as measured by optical coherence tomography angiography.

    Science.gov (United States)

    Lewis, Kyle T; Bullock, John R; Drumright, Ryan T; Olsen, Matthew J; Penman, Alan D

    2018-03-08

    The purpose is to evaluate the utility of optical coherence tomography (OCT) angiography in the evaluation of Graves' orbitopathy (GO) and response to orbital decompression in patients with and without dysthyroid optic neuropathy (DON). This was a single-center, prospective case series in a cohort of 12 patients (24 orbits) with GO and ±DON, (6 orbits) who underwent bilateral orbital decompression. All patients underwent pre- and postoperative OCT angiography of the peripapillary area. Vessel density indices were calculated in a 4.5 mm × 4.5 mm ellipsoid centered on the optic disk using split-spectrum amplitude decorrelation angiography algorithm, producing the vessel density measurements. Mean change in vessel density indices was compared between pre- and postoperative sessions and between patients with and without DON. Patient 1, a 34-year-old male with GO and unilateral DON OD, showed a significant reduction in blood vessel density indices oculus dexter (OD) (DON eye) after decompression while a more modest reduction was found oculus sinister (OS) with the greatest change noted intrapapillary. Patient 2, a 50-year-old male with DON OU, showed worsening neuropathy following decompression OD that was confirmed by angiographic density indices. Patient 3, a 55-year-female with DON, showed a reduction in blood vessel density OD and increased density OS. Patients without DON showed overall less impressive changes in indices as compared to those with DON. Using OCT angiography, response to surgical treatment in GO orbits, more so in orbits with DON, can be demonstrated and quantified using vessel density indices with reproducibility.

  8. Ultrastructural analysis of small blood vessels in skin biopsies in CADASIL

    Directory of Open Access Journals (Sweden)

    Lačković Vesna

    2008-01-01

    Full Text Available Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL is an inherited small- and medium-artery disease of the brain caused by mutation of the Notch3 gene. Very often, this disease is misdiagnosed. We examined skin biopsies in two members of the first discovered Serbian family affected by CADASIL. Electron microscopy showed that skin blood vessels of both patients contain numerous deposits of granular osmiophilic material (GOM around vascular smooth muscle cells (VSMCs. We observed degeneration of VSMCs, reorganization of their cytoskeleton and dense bodies, disruption of myoendothelial contacts, and apoptosis. Our results suggest that the presence of GOM in small skin arteries represents a specific marker in diagnosis of CADASIL.

  9. Distinct mechanisms of relaxation to bioactive components from chamomile species in porcine isolated blood vessels

    International Nuclear Information System (INIS)

    Roberts, R.E.; Allen, S.; Chang, A.P.Y.; Henderson, H.; Hobson, G.C.; Karania, B.; Morgan, K.N.; Pek, A.S.Y.; Raghvani, K.; Shee, C.Y.; Shikotra, J.; Street, E.; Abbas, Z.; Ellis, K.; Heer, J.K.; Alexander, S.P.H.

    2013-01-01

    German chamomile (Matricaria recutita L.), a widely-used herbal medicine, has been reported to have a wide range of biological effects, including smooth muscle relaxation. The aim of this study was to compare the effects of representative compounds from chamomile (apigenin, luteolin, (−)-α-bisabolol, farnesene, umbelliferone; 3–30 μM) on vascular tone using porcine coronary and splenic arteries mounted for isometric tension recording in isolated tissue baths and precontracted with the thromboxane-mimetic U46619. Apigenin, luteolin, and (−)-α-bisabolol produced slow, concentration-dependent relaxations in both the coronary and splenic arteries that were not blocked by inhibition of nitric oxide synthase or potassium channels. Removal of extracellular calcium inhibited the relaxations to all three compounds, and these compounds also inhibited calcium re-addition-evoked contractions, indicating that the relaxation response may be mediated through inhibition of calcium influx. Apigenin and luteolin, but not (−)-α-bisabolol, enhanced the relaxation to the nitric oxide donor sodium nitroprusside, indicating that apigenin and luteolin may act to regulate cyclic GMP levels. Umbelliferone produced a rapid, transient relaxation in the splenic artery, but not the coronary artery, that was inhibited by L-NAME and removal of the endothelium, suggesting an influence on nitric oxide production. Farnesene, at concentrations up to 30 μM, was without effect in either blood vessel. In conclusion, hydroxylated compounds (apigenin, luteolin and (−)-α-bisabolol) found in chamomile all caused a slow relaxation of isolated blood vessels through an effect on calcium influx. Umbelliferone, on the other hand, produced a rapid, transient relaxation dependent upon release of nitric oxide from the endothelium. - Highlights: • Apigenin, luteolin, and (-)-α-bisabolol are present in chamomile. • They produced slow, concentration-dependent relaxations in arteries. • These

  10. Chronic hydrocephalus-induced hypoxia: increased expression of VEGFR-2+ and blood vessel density in hippocampus.

    Science.gov (United States)

    Dombrowski, S M; Deshpande, A; Dingwall, C; Leichliter, A; Leibson, Z; Luciano, M G

    2008-03-18

    Chronic hydrocephalus (CH) is a neurological disease characterized by increased cerebrospinal fluid volume and pressure that is often associated with impaired cognitive function. By and large, CH is a complex and heterogeneous cerebrospinal fluid (CSF) disorder where the exact site of brain insult is uncertain. Several mechanisms including neural compression, fiber stretch, and local or global hypoxia have been implicated in the underlying pathophysiology of CH. Specifically, the hippocampus, which plays a significant role in memory processing and is in direct contact with expanding CSF ventricles, may be involved. Using our model of chronic hydrocephalus, we quantified the density of vascular endothelial growth factor receptor 2 (VEGFR-2(+)) neurons, glial, endothelial cells, and blood vessels in hippocampal regions CA1, CA2-3, dentate gyrus and hilus using immunohistochemical and stereological methods. Density and %VEGFR-2(+) cell populations were estimated for CH animals (2-3 weeks vs. 12-16 weeks) and surgical controls (SC). Overall, we found approximately six- to eightfold increase in the cellular density of VEGFR-2(+) and more than double blood vessel density (BVd) in the hippocampus of CH compared with SC. There were no significant regional differences in VEGFR-2(+) cellular and BVd expression in the CH group. VEGFR-2(+) and BVds were significantly related to changes in CSF volume (Pblood vessel expression was related to focal compression alone or in combination with global ischemia/hypoxia conditions as previously described. These findings suggest that VEGFR-2 may play an adaptive role in angiogenesis after CH

  11. Distinct mechanisms of relaxation to bioactive components from chamomile species in porcine isolated blood vessels

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, R.E., E-mail: Richard.roberts@nottingham.ac.uk; Allen, S.; Chang, A.P.Y.; Henderson, H.; Hobson, G.C.; Karania, B.; Morgan, K.N.; Pek, A.S.Y.; Raghvani, K.; Shee, C.Y.; Shikotra, J.; Street, E.; Abbas, Z.; Ellis, K.; Heer, J.K.; Alexander, S.P.H., E-mail: steve.alexander@nottingham.ac.uk

    2013-11-01

    German chamomile (Matricaria recutita L.), a widely-used herbal medicine, has been reported to have a wide range of biological effects, including smooth muscle relaxation. The aim of this study was to compare the effects of representative compounds from chamomile (apigenin, luteolin, (−)-α-bisabolol, farnesene, umbelliferone; 3–30 μM) on vascular tone using porcine coronary and splenic arteries mounted for isometric tension recording in isolated tissue baths and precontracted with the thromboxane-mimetic U46619. Apigenin, luteolin, and (−)-α-bisabolol produced slow, concentration-dependent relaxations in both the coronary and splenic arteries that were not blocked by inhibition of nitric oxide synthase or potassium channels. Removal of extracellular calcium inhibited the relaxations to all three compounds, and these compounds also inhibited calcium re-addition-evoked contractions, indicating that the relaxation response may be mediated through inhibition of calcium influx. Apigenin and luteolin, but not (−)-α-bisabolol, enhanced the relaxation to the nitric oxide donor sodium nitroprusside, indicating that apigenin and luteolin may act to regulate cyclic GMP levels. Umbelliferone produced a rapid, transient relaxation in the splenic artery, but not the coronary artery, that was inhibited by L-NAME and removal of the endothelium, suggesting an influence on nitric oxide production. Farnesene, at concentrations up to 30 μM, was without effect in either blood vessel. In conclusion, hydroxylated compounds (apigenin, luteolin and (−)-α-bisabolol) found in chamomile all caused a slow relaxation of isolated blood vessels through an effect on calcium influx. Umbelliferone, on the other hand, produced a rapid, transient relaxation dependent upon release of nitric oxide from the endothelium. - Highlights: • Apigenin, luteolin, and (-)-α-bisabolol are present in chamomile. • They produced slow, concentration-dependent relaxations in arteries. • These

  12. Characterization of serological neo-epitope biomarkers reflecting collagen remodeling in clinically stable chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Sand, Jannie M B; Martinez, Gerd; Midjord, Anne-Kirsten

    2016-01-01

    OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation that leads to excessive remodeling of the lung extracellular matrix (ECM), resulting in release of protein fragments (neo-epitopes) to the blood. Serological markers assessing this have previously been...... of COPD, blood oxygen saturation, shuttle walk test distance, GOLD grades, or CAT scores. CONCLUSIONS: Serological biomarkers of collagen remodeling were elevated in subjects with COPD as compared with healthy individuals. Biomarker levels were significantly correlated with measures of dyspnea, indicating...... a relationship with degree of symptoms, while only C6M showed a weak but significant association with lung function. Biomarker levels were not related to GOLD grades, which was in line with previous studies indicating that ECM remodeling may be related to disease activity rather than severity....

  13. Micropatterned coculture of vascular endothelial and smooth muscle cells on layered electrospun fibrous mats toward blood vessel engineering.

    Science.gov (United States)

    Li, Huinan; Liu, Yaowen; Lu, Jinfu; Wei, Jiaojun; Li, Xiaohong

    2015-06-01

    A major challenge in vascular engineering is the establishment of proper microenvironment to guide the spatial organization, growth, and extracellular matrix (ECM) productions of cells found in blood vessels. In the current study, micropatterned fibrous mats with distinct ridges and grooves of different width were created to load smooth muscle cells (SMCs), which were assembled by stacking on vascular endothelial cell (EC)-loaded flat fibrous mats to mimic the in vivo-like organized structure of blood vessels. SMCs were mainly distributed in the ridges, and aligned fibers in the patterned regions led to the formation of elongated cell bodies, intense actin filaments, and expressions of collagen I and α-smooth muscle actin in a parallel direction with fibers. ECs spread over the flat fibrous mats and expressed collagen IV and laminin with a cobblestone-like feature. A z-stack scanning of fluorescently stained fibrous mats indicated that SMCs effectively infiltrated into fibrous scaffolds at the depth of around 200 μm. Compared with SMCs cultured alone, the coculture with ECs enhanced the proliferation, infiltration, and cytoskeleton elongation of SMCs on patterned fibrous mats. Although the coculture of SMCs made no significant difference in the EC growth, the coculture system on patterned fibrous scaffolds promoted ECM productions of both ECs and SMCs. Thus, this patterned fibrous configuration not only offers a promising technology in the design of tissue engineering scaffolds to construct blood vessels with durable mechanical properties, but also provides a platform for patterned coculture to investigate cell-matrix and cell-cell interactions in highly organized tissues. © 2014 Wiley Periodicals, Inc.

  14. Adventitial gene transfer of catalase attenuates angiotensin II-induced vascular remodeling.

    Science.gov (United States)

    Liu, Cun-Fei; Zhang, Jia; Shen, Kai; Gao, Ping-Jin; Wang, Hai-Ya; Jin, Xin; Meng, Chao; Fang, Ning-Yuan

    2015-04-01

    Vascular adventitia and adventitia‑derived reactive oxygen species (ROS) contribute to vascular remodeling following vascular injury. A previous ex vivo study in adventitial fibroblasts showed that catalase, one of most important anti‑oxide enzymes, was downregulated by angiotensin II (AngII). The aim of the present study was to investigate whether adventitial gene transfer of catalase affects AngII‑induced vascular remodeling in vivo. Adenoviruses co‑expressing catalase and enhanced green fluorescent protein (eGFP) or expressing eGFP only were applied to the adventitial surface of common carotid arteries of Sprague‑Dawley rats. Alzet minipumps administering AngII (0.75 mg/kg/day) were then implanted subcutaneously for 14 days. Systolic blood pressure and biological parameters of vascular remodeling were measured in each group. Adventitial fibroblasts were cultured and p38 mitogen‑activated protein kinase (MAPK) phosphorylation was measured using western blot analysis. The results showed that adventitial gene transfer of catalase had no effect on AngII‑induced systolic blood pressure elevation. However, catalase adenovirus transfection significantly inhibited AngII‑induced media hypertrophy compared with that of the control virus (Padventitial α‑smooth muscle actin expression. Furthermore, catalase transfection significantly inhibited the AngII‑induced increase in p38MAPK phosphorylation. In conclusion, the results of the present study demonstrated that adventitial gene transfer of catalase significantly attenuated AngII‑induced vascular remodeling in rats via inhibition of adventitial p38MAPK phosphorylation.

  15. Cells involved in extracellular matrix remodeling after acute myocardial infarction

    International Nuclear Information System (INIS)

    Garcia, Larissa Ferraz; Mataveli, Fábio D’Aguiar; Mader, Ana Maria Amaral Antônio; Theodoro, Thérèse Rachell; Justo, Giselle Zenker; Pinhal, Maria Aparecida da Silva

    2015-01-01

    Evaluate the effects of VEGF_1_6_5 gene transfer in the process of remodeling of the extracellular matrix after an acute myocardial infarct. Wistar rats were submitted to myocardial infarction, after the ligation of the left descending artery, and the left ventricle ejection fraction was used to classify the infarcts into large and small. The animals were divided into groups of ten, according to the size of infarcted area (large or small), and received or not VEGF_1_6_5 treatment. Evaluation of different markers was performed using immunohistochemistry and digital quantification. The primary antibodies used in the analysis were anti-fibronectin, anti-vimentin, anti-CD44, anti-E-cadherin, anti-CD24, anti-alpha-1-actin, and anti-PCNA. The results were expressed as mean and standard error, and analyzed by ANOVA, considering statistically significant if p≤0.05. There was a significant increase in the expression of undifferentiated cell markers, such as fibronectin (protein present in the extracellular matrix) and CD44 (glycoprotein present in the endothelial cells). However, there was decreased expression of vimentin and PCNA, indicating a possible decrease in the process of cell proliferation after treatment with VEGF_1_6_5. Markers of differentiated cells, E-cadherin (adhesion protein between myocardial cells), CD24 (protein present in the blood vessels), and alpha-1-actin (specific myocyte marker), showed higher expression in the groups submitted to gene therapy, compared to non-treated group. The value obtained by the relation between alpha-1-actin and vimentin was approximately three times higher in the groups treated with VEGF_1_6_5, suggesting greater tissue differentiation. The results demonstrated the important role of myocytes in the process of tissue remodeling, confirming that VEGF_1_6_5 seems to provide a protective effect in the treatment of acute myocardial infarct

  16. Cells involved in extracellular matrix remodeling after acute myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, Larissa Ferraz [Faculdade de Medicina do ABC, Santo André, SP (Brazil); Mataveli, Fábio D’Aguiar [Universidade Federal de São Paulo, São Paulo, SP (Brazil); Mader, Ana Maria Amaral Antônio; Theodoro, Thérèse Rachell [Faculdade de Medicina do ABC, Santo André, SP (Brazil); Justo, Giselle Zenker; Pinhal, Maria Aparecida da Silva [Universidade Federal de São Paulo, São Paulo, SP (Brazil)

    2015-07-01

    Evaluate the effects of VEGF{sub 165} gene transfer in the process of remodeling of the extracellular matrix after an acute myocardial infarct. Wistar rats were submitted to myocardial infarction, after the ligation of the left descending artery, and the left ventricle ejection fraction was used to classify the infarcts into large and small. The animals were divided into groups of ten, according to the size of infarcted area (large or small), and received or not VEGF{sub 165} treatment. Evaluation of different markers was performed using immunohistochemistry and digital quantification. The primary antibodies used in the analysis were anti-fibronectin, anti-vimentin, anti-CD44, anti-E-cadherin, anti-CD24, anti-alpha-1-actin, and anti-PCNA. The results were expressed as mean and standard error, and analyzed by ANOVA, considering statistically significant if p≤0.05. There was a significant increase in the expression of undifferentiated cell markers, such as fibronectin (protein present in the extracellular matrix) and CD44 (glycoprotein present in the endothelial cells). However, there was decreased expression of vimentin and PCNA, indicating a possible decrease in the process of cell proliferation after treatment with VEGF{sub 165}. Markers of differentiated cells, E-cadherin (adhesion protein between myocardial cells), CD24 (protein present in the blood vessels), and alpha-1-actin (specific myocyte marker), showed higher expression in the groups submitted to gene therapy, compared to non-treated group. The value obtained by the relation between alpha-1-actin and vimentin was approximately three times higher in the groups treated with VEGF{sub 165}, suggesting greater tissue differentiation. The results demonstrated the important role of myocytes in the process of tissue remodeling, confirming that VEGF{sub 165} seems to provide a protective effect in the treatment of acute myocardial infarct.

  17. Effects of exercise training on pulmonary vessel muscularization and right ventricular function in an animal model of COPD.

    Science.gov (United States)

    Hassel, Erlend; Berre, Anne Marie; Skjulsvik, Anne Jarstein; Steinshamn, Sigurd

    2014-09-28

    Right ventricular dysfunction in COPD is common, even in the absence of pulmonary hypertension. The aim of the present study was to examine the effects of high intensity interval training (HIIT) on right ventricular (RV) function, as well as pulmonary blood vessel remodeling in a mouse model of COPD. 42 female A/JOlaHsd mice were randomized to exposure to either cigarette smoke or air for 6 hours/day, 5 days/week for 14 weeks. Mice from both groups were further randomized to sedentariness or HIIT for 4 weeks. Cardiac function was evaluated by echocardiography and muscularization of pulmonary vessel walls by immunohistochemistry. Smoke exposure induced RV systolic dysfunction demonstrated by reduced tricuspid annular plane systolic excursion. HIIT in smoke-exposed mice reversed RV dysfunction. There were no significant effects on the left ventricle of neither smoke exposure nor HIIT. Muscularization of the pulmonary vessels was reduced after exercise intervention, but no significant effects on muscularization were observed from smoke exposure. RV function was reduced in mice exposed to cigarette smoke. No Increase in pulmonary vessel muscularization was observed in these mice, implying that other mechanisms caused the RV dysfunction. HIIT attenuated the RV dysfunction in the smoke exposed mice. Reduced muscularization of the pulmonary vessels due to HIIT suggests that exercise training not only affects the heart muscle, but also has important effects on the pulmonary vasculature.

  18. Impact of positive and negative lesion site remodeling on clinical outcomes: insights from PROSPECT.

    Science.gov (United States)

    Inaba, Shinji; Mintz, Gary S; Farhat, Naim Z; Fajadet, Jean; Dudek, Dariusz; Marzocchi, Antonio; Templin, Barry; Weisz, Giora; Xu, Ke; de Bruyne, Bernard; Serruys, Patrick W; Stone, Gregg W; Maehara, Akiko

    2014-01-01

    This study investigated coronary artery remodeling patterns associated with clinical outcomes. In the prospective, multicenter PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree: An Imaging Study in Patients With Unstable Atherosclerotic Lesions) study, reported predictors of nonculprit lesion (NCL) major adverse cardiac events (MACE) were an intravascular ultrasound (IVUS) minimal lumen area (MLA) ≤4 mm(2), a plaque burden ≥70%, and a IVUS-virtual histology (VH) thin-cap fibroatheroma (TCFA), but not lesion site remodeling. Overall, 697 consecutive patients with an acute coronary syndrome were enrolled and underwent 3-vessel gray-scale and IVUS-VH; 3,223 NCLs were identified by IVUS. The remodeling index (RI) was calculated as the external elastic membrane area at the MLA site divided by the average of the proximal and distal reference external elastic membrane areas. First, one third of the patients were randomly selected to determine RI cutoffs related to NCL MACE (development cohort). Receiver-operating characteristic analysis showed that there were 2 separate cut points that predicted NCL MACE: RI = 0.8789 and RI = 1.0046 (area under the curve = 0.663). These cut points were used to define negative remodeling as an RI 1.00. Second, we used the remaining two-thirds of patients to validate these cut points with respect to lesion morphology and clinical outcomes (validation cohort). Kaplan-Meier curve analysis in the validation cohort showed that NCL MACE occurred more frequent (and equally) in negative and positive remodeling lesions compared with intermediate remodeling lesions. In this cohort, negative remodeling lesions had the smallest MLA, positive remodeling lesions had the largest plaque burden, and VH TCFA, especially VH TCFA with multiple necrotic cores, was most common in negatively remodeling lesions. The present study showed the novel concept that positive and negative lesion site remodeling was

  19. Treatment of hepatocellular carcinoma adjacent to large blood vessels using 1.5T MRI-guided percutaneous radiofrequency ablation combined with iodine-125 radioactive seed implantation

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Zheng-Yu, E-mail: linsinlan@yahoo.com.cn [The Department of Radiology, First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou 350005 (China); Chen, Jin, E-mail: snow8968851@163.com [The Department of Radiology, First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou 350005 (China); Deng, Xiu-Fen, E-mail: dxf197286@yahoo.com.cn [The Department of Radiology, First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou 350005 (China)

    2012-11-15

    Objective: The objective is to study the technology associated with and feasibility of the treatment of hepatocellular carcinoma (HCC) adjacent to large blood vessels using 1.5T MRI-guided radiofrequency ablation combined with iodine-125 (I-125) radioactive seed implantation. Methods: Sixteen patients with a total of 24 HCC lesions (average maximum diameter: 2.35 {+-} 1.03 cm) were pathologically confirmed by biopsy or clinically diagnosed received 1.5T MRI-guided percutaneous radiofrequency ablation (RFA) treatment. Each patient had one lesion adjacent to large blood vessels ({>=}3 mm); after the ablation, I-125 radioactive seeds were implanted in the portions of the lesions that were adjacent to the blood vessels. Results: All the ablations and I-125 radioactive seed implantations were successful; a total of 118 seeds were implanted. The ablated lesions exhibited hypointense signals on the T2WI sequence with a thin rim of hyperintense signals; they also exhibited significant hyperintense signals on the T1WI sequence with clear boundaries. The average follow-up period was 11.1 {+-} 6.2 months. There were 23 complete responses and one partial response in the 24 lesions. The alpha-fetoprotein (AFP) levels of the patients significantly decreased. Conclusion: The 1.5T MRI-guided RFA combined with I-125 radioactive seed implantation for the treatment of HCC adjacent to large blood vessels is an effective technology.

  20. Blood vessel endothelium-directed tumor cell streaming in breast tumors requires the HGF/C-Met signaling pathway.

    Science.gov (United States)

    Leung, E; Xue, A; Wang, Y; Rougerie, P; Sharma, V P; Eddy, R; Cox, D; Condeelis, J

    2017-05-11

    During metastasis to distant sites, tumor cells migrate to blood vessels. In vivo, breast tumor cells utilize a specialized mode of migration known as streaming, where a linear assembly of tumor cells migrate directionally towards blood vessels on fibronectin-collagen I-containing extracellular matrix (ECM) fibers in response to chemotactic signals. We have successfully reconstructed tumor cell streaming in vitro by co-plating tumors cells, macrophages and endothelial cells on 2.5 μm thick ECM-coated micro-patterned substrates. We found that tumor cells and macrophages, when plated together on the micro-patterned substrates, do not demonstrate sustained directional migration in only one direction (sustained directionality) but show random bi-directional walking. Sustained directionality of tumor cells as seen in vivo was established in vitro when beads coated with human umbilical vein endothelial cells were placed at one end of the micro-patterned 'ECM fibers' within the assay. We demonstrated that these endothelial cells supply the hepatocyte growth factor (HGF) required for the chemotactic gradient responsible for sustained directionality. Using this in vitro reconstituted streaming system, we found that directional streaming is dependent on, and most effectively blocked, by inhibiting the HGF/C-Met signaling pathway between endothelial cells and tumor cells. Key observations made with the in vitro reconstituted system implicating C-Met signaling were confirmed in vivo in mammary tumors using the in vivo invasion assay and intravital multiphoton imaging of tumor cell streaming. These results establish HGF/C-Met as a central organizing signal in blood vessel-directed tumor cell migration in vivo and highlight a promising role for C-Met inhibitors in blocking tumor cell streaming and metastasis in vivo, and for use in human trials.

  1. A remodelling metric for angular fibre distributions and its application to diseased carotid bifurcations.

    LENUS (Irish Health Repository)

    Creane, Arthur

    2012-07-01

    Many soft biological tissues contain collagen fibres, which act as major load bearing constituents. The orientation and the dispersion of these fibres influence the macroscopic mechanical properties of the tissue and are therefore of importance in several areas of research including constitutive model development, tissue engineering and mechanobiology. Qualitative comparisons between these fibre architectures can be made using vector plots of mean orientations and contour plots of fibre dispersion but quantitative comparison cannot be achieved using these methods. We propose a \\'remodelling metric\\' between two angular fibre distributions, which represents the mean rotational effort required to transform one into the other. It is an adaptation of the earth mover\\'s distance, a similarity measure between two histograms\\/signatures used in image analysis, which represents the minimal cost of transforming one distribution into the other by moving distribution mass around. In this paper, its utility is demonstrated by considering the change in fibre architecture during a period of plaque growth in finite element models of the carotid bifurcation. The fibre architecture is predicted using a strain-based remodelling algorithm. We investigate the remodelling metric\\'s potential as a clinical indicator of plaque vulnerability by comparing results between symptomatic and asymptomatic carotid bifurcations. Fibre remodelling was found to occur at regions of plaque burden. As plaque thickness increased, so did the remodelling metric. A measure of the total predicted fibre remodelling during plaque growth, TRM, was found to be higher in the symptomatic group than in the asymptomatic group. Furthermore, a measure of the total fibre remodelling per plaque size, TRM\\/TPB, was found to be significantly higher in the symptomatic vessels. The remodelling metric may prove to be a useful tool in other soft tissues and engineered scaffolds where fibre adaptation is also present.

  2. Blood vessel-based liver segmentation through the portal phase of a CT dataset

    Science.gov (United States)

    Maklad, Ahmed S.; Matsuhiro, Mikio; Suzuki, Hidenobu; Kawata, Yoshiki; Niki, Noboru; Moriyama, Noriyuki; Utsunomiya, Toru; Shimada, Mitsuo

    2013-02-01

    Blood vessels are dispersed throughout the human body organs and carry unique information for each person. This information can be used to delineate organ boundaries. The proposed method relies on abdominal blood vessels (ABV) to segment the liver considering the potential presence of tumors through the portal phase of a CT dataset. ABV are extracted and classified into hepatic (HBV) and nonhepatic (non-HBV) with a small number of interactions. HBV and non-HBV are used to guide an automatic segmentation of the liver. HBV are used to individually segment the core region of the liver. This region and non-HBV are used to construct a boundary surface between the liver and other organs to separate them. The core region is classified based on extracted posterior distributions of its histogram into low intensity tumor (LIT) and non-LIT core regions. Non-LIT case includes normal part of liver, HBV, and high intensity tumors if exist. Each core region is extended based on its corresponding posterior distribution. Extension is completed when it reaches either a variation in intensity or the constructed boundary surface. The method was applied to 80 datasets (30 Medical Image Computing and Computer Assisted Intervention (MICCAI) and 50 non-MICCAI data) including 60 datasets with tumors. Our results for the MICCAI-test data were evaluated by sliver07 [1] with an overall score of 79.7, which ranks seventh best on the site (December 2013). This approach seems a promising method for extraction of liver volumetry of various shapes and sizes and low intensity hepatic tumors.

  3. Design and development of a blood vessel localization system using a Nir viewer

    International Nuclear Information System (INIS)

    Hernandez R, A.; Plascencia C, L. E.; Cordova F, T.; Padilla R, N.

    2017-10-01

    In addition to the multiple applications of ionizing radiation in clinical diagnosis there is the possibility of using another part of the electromagnetic spectrum such as near infrared (Nir). This paper presents the design and construction of a Nir Biosensor in a range between 800 and 900 nm, which allows the visualization of blood vessels for the venepuncture procedure with the aim of reducing the trauma of venous access to patients of all ages. The possibility that the device is used in the location of venous ulcers as an alternative to veno grams obtained by X-rays is also explored. (Author)

  4. Remote non-invasive stereoscopic imaging of blood vessels: first in-vivo results of a new multispectral contrast enhancement technology

    NARCIS (Netherlands)

    Wieringa, F.P.; Mastik, F.; Cate, F.J. ten; Neumann, H.A.M.; Steen, A.F.W. van der

    2006-01-01

    We describe a contactless optical technique selectively enhancing superficial blood vessels below variously pigmented intact human skin by combining images in different spectral bands. Two CMOS-cameras, with apochromatic lenses and dual-band LED-arrays, simultaneously streamed Left (L) and Right (R)

  5. 3-D MDT with spherical targets by bilinear interpolation for determining blood velocity profiles including the vessel wall effect

    Science.gov (United States)

    Choomphon-anomakhun, Natthaphon; Natenapit, Mayuree

    2018-02-01

    A numerical simulation of three-dimensional (3-D) implant assisted-magnetic drug targeting (IA-MDT) using ferromagnetic spherical targets, including the effect from the vessel wall on the blood flow, is presented. The targets were implanted within arterioles and subjected to an externally uniform applied magnetic field in order to increase the effectiveness of targeting magnetic drug carrier particles (MDCPs). The capture area (As) of the MDCPs was determined by inspection of the particle trajectories simulated from the particle equations of motion. The blood flow velocities at any particle position around the target were obtained by applying bilinear interpolation to the numerical blood velocity data. The effects on As of the type of ferromagnetic materials in the targets and MDCPs, average blood flow rates, mass fraction of the ferromagnetic material in the MDCPs, average radii of MDCPs (Rp) and the externally applied magnetic field strength (μ0H0) were evaluated. Furthermore, the appropriate μ0H0 and Rp for the IA-MDT design is suggested. In the case of the SS409 target and magnetite MDCPs, dimensionless capture areas ranging from 4.1- to 12.4 and corresponding to particle capture efficiencies of 31-94% were obtained with Rp ranging from 100- to 500 nm, weight fraction of 80%, μ0H0 of 0.6 T and an average blood flow rate of 0.01 ms-1. In addition, the more general 3-D modelling of IA-MDT in this work is applicable to IA-MDT using spherical targets implanted within blood vessels for both laminar and potential blood flows including the wall effect.

  6. Ultrastructure of Pericystic or Intracystic Blood Vessels in Epidermoid Cysts-A Transmission Electron Microscopy Study: Laboratory Investigation.

    Science.gov (United States)

    Ren, Xiao-Hui; Ma, Jun; Zeng, Chun; Sun, Yi-Lin; Lin, Song

    2017-07-01

    Recently, we reported a tendency toward spontaneous hemorrhage in both the preoperative and postoperative periods in patients with intracranial epidermoid cyst (EC). According to our experience, this tendency for spontaneous hemorrhage was partly caused by the pathologic blood vessels adjacent to the EC. This study was designed to testify this hypothesis. Twenty-three removable pericystic or intracystic blood vessels from 17 patients with EC were collected during surgery and were then examined by transmission electron microscopy. The microvascular structure in gliomas was chosen as the control. Under electron microscopy, variant pathologic changes of vessels were found in all patients with EC. In the tunicae intima, we found vacuolization, apoptosis, necrosis, and intralumenal protrusion of endothelial cells, as well as swollen basement and highly flexed and discontinued elastic plate. In the tunicae media, vacuolization and swollen mitochondria were found in muscular cells. In the tunicae adventitia, extravascular erythrocytes, edema or apoptosis of pericytes, collagen predominance, and inflammatory cell infiltration and destruction were found. Neuron denature and necrosis were found in the peripheral brain tissue. In the microvascular structure of 5 glioma specimens, we found enlargement and hyperplasia of endothelial cells, swollen basement membrane, swollen pericytes, and astrocytic hyperplasia and neuron denature in adjacent brain tissues. Our findings provide strong evidence for the hypothesis that intracystic or pericystic vascular degeneration or destruction accounts for the spontaneous hemorrhage tendency before and after surgical resection of ECs. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Inherited neurovascular diseases affecting cerebral blood vessels and smooth muscle.

    Science.gov (United States)

    Sam, Christine; Li, Fei-Feng; Liu, Shu-Lin

    2015-10-01

    Neurovascular diseases are among the leading causes of mortality and permanent disability due to stroke, aneurysm, and other cardiovascular complications. Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and Marfan syndrome are two neurovascular disorders that affect smooth muscle cells through accumulation of granule and osmiophilic materials and defective elastic fiber formations respectively. Moyamoya disease, hereditary hemorrhagic telangiectasia (HHT), microcephalic osteodysplastic primordial dwarfism type II (MOPD II), and Fabry's disease are disorders that affect the endothelium cells of blood vessels through occlusion or abnormal development. While much research has been done on mapping out mutations in these diseases, the exact mechanisms are still largely unknown. This paper briefly introduces the pathogenesis, genetics, clinical symptoms, and current methods of treatment of the diseases in the hope that it can help us better understand the mechanism of these diseases and work on ways to develop better diagnosis and treatment.

  8. Effects of High-sugar and High-fat Diet on Fat Deposition and Blood Vessel Wall on Sprague Dawley Rats Liver

    Directory of Open Access Journals (Sweden)

    Vera Citra Setiawan Hoei

    2013-11-01

    Full Text Available People nowadays tend to consume more fast food and sweetened beverages. These foods usually contain high amount sugar and fat that have effects on the body including liver.This study was conducted to explore the effects of extensive intake of sugar and fat on blood glucose and  cholesterol level as well as changes in liver. Research was conducted with experimental method using 20 Sprague Dawley rats which were divided into 4 groups; 2 controls and 2 treatments. Rats were given 5 ml sugar or lard alternatively every 2 consecutive days for 1-month and 2-month respectively. Data was retrieved include blood glucose and cholesterol level, fatty liver percentage and blood vessel thickening after intervention through HE staining. The results showed that both 1-month and 2-month intervention group has significant increase in blood glucose and cholesterol level. However, the enhancement of fatty liver percentage and number of thickened blood vessels (p<0.05 were only foundsignificant (p<0.05 in 1-month intervention group.  We concluded that high intake of sugar and fat within 1-monthintervention have significant effects on the rat body including liver. Nevertheless, it was not found significant in 2-months intervention. Further studies are still needed to analyze this incongruent result.Key words: high-sugar diet, high-fat diet, fatty liver, atherosclerosis 

  9. Evaluation of coronary artery remodeling in patients with acute coronary syndrome and stable angina by multislice computed tomography

    International Nuclear Information System (INIS)

    Imazeki, Takako; Sato, Yuichi; Inoue, Fumio; Anazawa, Takeo; Tani, Shigemasa; Matsumoto, Naoya; Takayama, Tadateru; Uchiyama, Takahisa; Saito, Satoshi

    2004-01-01

    Multislice computed tomography (MSCT) was used to evaluate coronary artery remodeling in patients with acute coronary syndrome (ACS) and stable angina (SA). MSCT was performed in 31 patients with ACS and 26 patients with SA and intravascular ultrasound (IVUS) was performed in 28 of these 57 patients. In both the MSCT and IVUS analyses, coronary artery remodeling was assessed by the remodeling index (RI): RI>1.10 was defined as positive coronary artery remodeling (PCAR) and RI<0.95 was defined as negative coronary artery remodeling (NCAR). The RI assessed by MSCT closely correlated with that of IVUS (r=0.86, n=28). The vessel area at the region of maximum luminal narrowing was also comparable between the MSCT and IVUS measurements (r=0.92). PCAR was present in 19 patients (61.3%) with ACS, but in none of the patients with SA (p<0.0001). However, NCAR was present in only 1 patient with ACS (3.2%), but was present in 18 patients (62.9%) with SA. The RI was significantly larger in patients with ACS (1.19±0.18) than in those with SA (0.89±0.10, p<0.0001). MSCT accurately assesses coronary artery remodeling. (author)

  10. PolNet: A Tool to Quantify Network-Level Cell Polarity and Blood Flow in Vascular Remodeling.

    Science.gov (United States)

    Bernabeu, Miguel O; Jones, Martin L; Nash, Rupert W; Pezzarossa, Anna; Coveney, Peter V; Gerhardt, Holger; Franco, Claudio A

    2018-05-08

    In this article, we present PolNet, an open-source software tool for the study of blood flow and cell-level biological activity during vessel morphogenesis. We provide an image acquisition, segmentation, and analysis protocol to quantify endothelial cell polarity in entire in vivo vascular networks. In combination, we use computational fluid dynamics to characterize the hemodynamics of the vascular networks under study. The tool enables, to our knowledge for the first time, a network-level analysis of polarity and flow for individual endothelial cells. To date, PolNet has proven invaluable for the study of endothelial cell polarization and migration during vascular patterning, as demonstrated by two recent publications. Additionally, the tool can be easily extended to correlate blood flow with other experimental observations at the cellular/molecular level. We release the source code of our tool under the Lesser General Public License. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  11. Perivascular delivery of Notch 1 siRNA inhibits injury-induced arterial remodeling.

    Directory of Open Access Journals (Sweden)

    Eileen M Redmond

    Full Text Available To determine the efficacy of perivascular delivery of Notch 1 siRNA in preventing injury-induced arterial remodeling.Carotid artery ligation was performed to induce arterial remodeling. After 14 days, morphometric analysis confirmed increased vSMC growth and subsequent media thickening and neointimal formation. Laser capture microdissection, quantitative qRT-PCR and immunoblot analysis of medial tissue revealed a significant increase in Notch1 receptor and notch target gene, Hrt 1 and 2 expression in the injured vessels. Perivascular delivery of Notch 1 siRNA by pluronic gel inhibited the injury-induced increase in Notch 1 receptor and target gene expression when compared to scrambled siRNA controls while concomitantly reducing media thickening and neointimal formation to pre-injury, sham-operated levels. Selective Notch 1 knockdown also reversed the injury-induced inhibition of pro-apoptotic Bax expression while decreasing injury-induced anti-apoptotic Bcl-XL expression to sham-operated control levels. In parallel experiments, proliferative cyclin levels, as measured by PCNA expression, were reversed to sham-operated control levels following selective Notch 1 knockdown.These results suggest that injury-induced arterial remodeling can be successfully inhibited by localized perivascular delivery of Notch 1 siRNA.

  12. Adenoviral short hairpin RNA therapy targeting phosphodiesterase 5a relieves cardiac remodeling and dysfunction following myocardial infarction

    Science.gov (United States)

    Li, Longhu; Haider, Husnain Kh.; Wang, Linlin; Lu, Gang

    2012-01-01

    We previously showed that treatment with tadalafil, a long-acting phosphodiesterase-5a (PDE5a) inhibitor, effectively prevented adverse left ventricular (LV) remodeling of the infarcted heart. We hypothesized that short-hairpin RNA (shRNA) therapy targeting PDE5a would simulate the effects of pharmacological intervention for treatment of postinfarction LV remodeling and dysfunction. Experimental model of myocardial infarction was developed in female mice by permanent ligation of left coronary artery. Immediately after that, an adenoviral vector encoding for shRNA sequence targeting PDE5a (Ad-shPDE5a) was injected intramyocardially, which specifically inhibited PDE5a in the heart. Four weeks later, Ad-shPDE5a treated mice showed significant mitigation of the left ventricle (LV) dilatation and dysfunction as indicated by smaller LV cavity and more preserved ejection fraction and fractional shortening. Infarction size and fibrosis were significantly reduced in Ad-shPDE5a-treated mice. Additionally, more salvaged cardiomyocytes, significantly reduced collagen contents, and higher blood vessel density were observed in Ad-shPDE5a-treated mice. The cytoprotective effects of Ad-shPDE5a were demonstrated in vitro in Ad-shPDE5a transfected cardiomyocytes cultured under oxygen glucose deprivation. Among downstream mediators of PDE5a signaling, cyclic GMP (cGMP) and cGMP-dependent protein kinase G (PKG) were activated with concomitant reduction in caspase-3 activity. However, no significant change in PKA and cAMP activities were observed in Ad-shPDE5a-treated hearts. Inhibition with shRNA improved cardiac remodeling and dysfunction by reducing infarction size and cardiac fibrosis and increased cGMP and PKG activity. These findings suggest that PDE5 inhibition with Ad-shPDE5a is a novel approach for treatment of myocardial infarction. PMID:22447941

  13. The absorbed dose to blood from blood-borne activity

    International Nuclear Information System (INIS)

    Hänscheid, H; Fernández, M; Lassmann, M

    2015-01-01

    The radiation absorbed dose to blood and organs from activity in the blood is relevant for nuclear medicine dosimetry and for research in biodosimetry. The present study provides coefficients for the average absorbed dose rates to the blood from blood-borne activity for radionuclides frequently used in targeted radiotherapy and in PET diagnostics. The results were deduced from published data for vessel radius-dependent dose rate coefficients and reasonable assumptions on the blood-volume distribution as a function of the vessel radius. Different parts of the circulatory system were analyzed separately. Vessel size information for heart chambers, aorta, vena cava, pulmonary artery, and capillaries was taken from published results of morphometric measurements. The remaining blood not contained in the mentioned vessels was assumed to reside in fractal-like vascular trees, the smallest branches of which are the arterioles or venules. The applied vessel size distribution is consistent with recommendations of the ICRP on the blood-volume distribution in the human. The resulting average absorbed dose rates to the blood per nuclear disintegration per milliliter (ml) of blood are (in 10 −11  Gy·s −1 ·Bq −1 ·ml) Y-90: 5.58, I-131: 2.49, Lu-177: 1.72, Sm-153: 2.97, Tc-99m: 0.366, C-11: 4.56, F-18: 3.61, Ga-68: 5.94, I-124: 2.55. Photon radiation contributes 1.1–1.2·10 −11  Gy·s −1 ·Bq −1 ·ml to the total dose rate for positron emitters but significantly less for the other nuclides. Blood self-absorption of the energy emitted by ß-particles in the whole blood ranges from 37% for Y-90 to 80% for Tc-99m. The correspondent values in vascular trees, which are important for the absorbed dose to organs, range from 30% for Y-90 to 82% for Tc-99m. (paper)

  14. Dilated thin-walled blood and lymphatic vessels in human endometrium: a potential role for VEGF-D in progestin-induced break-through bleeding.

    Directory of Open Access Journals (Sweden)

    Jacqueline F Donoghue

    Full Text Available Progestins provide safe, effective and cheap options for contraception as well as the treatment of a variety of gynaecological disorders. Episodes of irregular endometrial bleeding or breakthrough bleeding (BTB are a major unwanted side effect of progestin treatment, such that BTB is the leading cause for discontinued use of an otherwise effective and popular medication. The cellular mechanisms leading to BTB are poorly understood. In this study, we make the novel finding that the large, dilated, thin walled vessels characteristic of human progestin-treated endometrium include both blood and lymphatic vessels. Increased blood and lymphatic vessel diameter are features of VEGF-D action in other tissues and we show by immunolocalisation and Western blotting that stromal cell decidualisation results in a significant increase in VEGF-D protein production, particularly of the proteolytically processed 21 kD form. Using a NOD/scid mouse model with xenografted human endometrium we were able to show that progestin treatment causes decidualisation, VEGF-D production and endometrial vessel dilation. Our results lead to a novel hypothesis to explain BTB, with stromal cell decidualisation rather than progestin treatment per se being the proposed causative event, and VEGF-D being the proposed effector agent.

  15. Development of a system for measuring wall shear stress in blood vessels using magnetic resonance imaging and computational fluid dynamics

    International Nuclear Information System (INIS)

    Yoshida, Keita; Nagao, Taisuke; Okada, Kouji; Miyazaki, Shohei; Yang, Xiaomei; Yamazaki, Youichi; Murase, Kenya

    2008-01-01

    We developed a system for measuring the wall shear stress (WSS) in blood vessels using magnetic resonance imaging (MRI) and computational fluid dynamics (CFD). The time-dependent velocity at the center of the blood vessel was measured by phase-contrast MRI and was approximated by finite Fourier series, which was used for generating the velocity profile at the inlet for the boundary condition to the CFD method. To validate the CFD method, we compared the WSS obtained by the CFD method with the theoretical value in a straight cylinder with various radii for both steady and pulsatile flows. We also investigated the dependence of the WSS on the inlet velocity profile incorporated into the CFD method. For steady flow, there was a good agreement between the WSS obtained by the CFD method and the theoretical value. For pulsatile flow, there was a relatively good agreement between them when the radius of the cylinder was 2.5 mm and the inlet velocity profile was given by the Womersley solution for fully developed pulsatile flow in a straight circular cylinder. When the radius of the cylinder was 5 mm and/or the inlet velocity profile was assumed to be parabolic, large differences were observed between them, suggesting that the assumption of fully developed flow does not hold true in these cases. In human studies, the vortex due to the secondary blood flow in the carotid arterial sinus was clearly observed. The WSS in the bifurcation was the highest, while that in the carotid arterial sinus was the smallest. In conclusion, the system presented here appears to be useful for measuring the WSS in blood vessels and for analyzing the cause and/or extent of atherosclerosis, and our results suggest that the inlet velocity profile should be carefully considered. (author)

  16. Blood vessel formation during tail regeneration in the leopard gecko (Eublepharis macularius): The blastema is not avascular.

    Science.gov (United States)

    Payne, Samantha L; Peacock, Hanna M; Vickaryous, Matthew K

    2017-03-01

    Unique among amniotes, many lizards are able to self-detach (autotomize) their tail and then regenerate a replacement. Tail regeneration involves the formation of a blastema, an accumulation of proliferating cells at the site of autotomy. Over time, cells of the blastema give rise to most of the tissues in the replacement tail. In non-amniotes capable of regenerating (such as urodeles and some teleost fish), the blastema is reported to be essentially avascular until tissue differentiation takes place. For tail regenerating lizards less is known. Here, we investigate neovascularization during tail regeneration in the leopard gecko (Eublepharis macularius). We demonstrate that the gecko tail blastema is not an avascular structure. Beginning with the onset of regenerative outgrowth, structurally mature (mural cell supported) blood vessels are found within the blastema. Although the pattern of blood vessel distribution in the regenerate tail differs from that of the original, a hierarchical network is established, with vessels of varying luminal diameters and wall thicknesses. Using immunostaining, we determine that blastema outgrowth and tissue differentiation is characterized by a dynamic interplay between the pro-angiogenic protein vascular endothelial growth factor (VEGF) and the anti-angiogenic protein thrombospondin-1 (TSP-1). VEGF-expression is initially widespread, but diminishes as tissues differentiate. In contrast, TSP-1 expression is initially restricted but becomes more abundant as VEGF-expression wanes. We predict that variation in the neovascular response observed between different regeneration-competent species likely relates to the volume of the blastema. J. Morphol. 278:380-389, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  17. Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems

    CERN Document Server

    Thiriet, Marc

    2013-01-01

    The volumes in this authoritative series present a multidisciplinary approach to modeling and simulation of flows in the cardiovascular and ventilatory systems, especially multiscale modeling and coupled simulations. Volume 5 is devoted to cells, tissues, and organs of the cardiovascular and ventilatory systems with an emphasis on mechanotransduction-based regulation of flow. The blood vessel wall is a living tissue that quickly reacts to loads applied on it by the flowing blood. In any segment of a blood vessel, the endothelial and smooth muscle cells can sense unusual time variations in small-magnitude wall shear stress and large-amplitude wall stretch generated by abnormal hemodynamic stresses. These cells respond with a short-time scale (from seconds to hours) to adapt the vessel caliber. Since such adaptive cell activities can be described using mathematical models, a key objective of this volume is to identify the mesoscopic agents and nanoscopic mediators required to derive adequate mathematical models...

  18. Energetic and spatial constraints of arterial networks

    Directory of Open Access Journals (Sweden)

    Sandro Rossitti

    1995-06-01

    Full Text Available The principle of minimum work (PMW is a parametric optimization model for the growth and adaptation of arterial trees. A balance between energy dissipation due to frictional resistance of laminar flow (shear stress and the minimum volume of the blood and vessel wall tissue is achieved when the vessel radii are adjusted to the cube root of the volumetric flow. The PMW is known to apply over several magnitudes of vessel calibers, and in many different organs, including the brain, in humans and in animals. Animal studies suggest that blood flow in arteries is approximately proportional to the cube of the vessel radius, and that arteries alter their caliber in response to sustained changes of blood flow according to PMW. Remodelling of the retinal arteriolar network to long-term changes in blood flow was observed in humans. Remodelling of whole arterial networks occurs in the form of increase or diminishing of vessel calibers. Shear stress induced endothelial mediation seems to be the regulating mechanism for the maintenance of this optimum blood flow/vessel diameter relation. Arterial trees are also expected to be nearly space filing. The vascular system is constructed in such a way that, while blood vessels occupy only a small percentage of the body volume leaving the bulk to tissue, they also crisscross organs so tightly that every point in the tissue lies on the boundary between an artery and a vein. This review describes how the energetic optimum principle for least energy cost for blood flow is also compatible with the spatial constraints of arterial networks according to concepts derived from fractal geometry.

  19. Pentoxifylline Attenuates Cardiac Remodeling Induced by Tobacco Smoke Exposure

    Energy Technology Data Exchange (ETDEWEB)

    Minicucci, Marcos; Oliveira, Fernando; Santos, Priscila; Polegato, Bertha; Roscani, Meliza; Fernandes, Ana Angelica; Lustosa, Beatriz; Paiva, Sergio; Zornoff, Leonardo; Azevedo, Paula, E-mail: paulasa@fmb.unesp.br [Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, São Paulo, SP (Brazil)

    2016-05-15

    Tobacco smoke exposure is an important risk factor for cardiac remodeling. Under this condition, inflammation, oxidative stress, energy metabolism abnormalities, apoptosis, and hypertrophy are present. Pentoxifylline has anti‑inflammatory, anti-apoptotic, anti-thrombotic and anti-proliferative properties. The present study tested the hypothesis that pentoxifylline would attenuate cardiac remodeling induced by smoking. Wistar rats were distributed in four groups: Control (C), Pentoxifylline (PX), Tobacco Smoke (TS), and PX-TS. After two months, echocardiography, invasive blood pressure measurement, biochemical, and histological studies were performed. The groups were compared by two-way ANOVA with a significance level of 5%. TS increased left atrium diameter and area, which was attenuated by PX. In the isolated heart study, TS lowered the positive derivate (+dp/dt), and this was attenuated by PX. The antioxidants enzyme superoxide dismutase and glutathione peroxidase were decreased in the TS group; PX recovered these activities. TS increased lactate dehydrogenase (LDH) and decreased 3-hydroxyacyl Coenzyme A dehydrogenases (OH-DHA) and citrate synthase (CS). PX attenuated LDH, 3-OH-DHA and CS alterations in TS-PX group. TS increased IL-10, ICAM-1, and caspase-3. PX did not influence these variables. TS induced cardiac remodeling, associated with increased inflammation, oxidative stress, apoptosis, and changed energy metabolism. PX attenuated cardiac remodeling by reducing oxidative stress and improving cardiac bioenergetics, but did not act upon cardiac cytokines and apoptosis.

  20. Fronto-Orbital Advancement and Total Calvarial Remodelling for Craniosynostosis

    International Nuclear Information System (INIS)

    Haq, E. U.; Aman, S.; Tammimy, M. S.; Ahmad, R. S.

    2014-01-01

    Objective: To describe the results of fronto-orbital advancement and remodelling for craniosynostosis in children. Study Design: Case series. Place and Duration of Study: Department of Plastic Surgery, Combined Military Hospital, Rawalpindi, from June 2009 to June 2012. Methodology: All the patients with cranial suture synostosis operated were included in the study. Those patients who were lost to follow-up were excluded. Variables considered were age, gender, type of synostosis, intracranial pressure, and history of previous surgeries for the same problem. Outcome measures were studied in terms of improvement of skull measurements (anteroposterior and bicoronal), duration of surgery, hospital stay, blood transfusions, complications and parents satisfaction. Results: A total of 36 patients were included in the study. Male to female ratio was 3:1. The age ranged from 5 to 54 months. Thirty two patients presented with non-syndromic and four with syndromic craniosynostosis. Fronto orbital advancement and total calvarial remodelling was done in 26 and 10 patients respectively. There was improvement in the skull measurements and the parents were satisfied in all cases with the skull shape. Complications occurred in 11.1% including chest and wound infection and one death. Conclusion: Fronto-orbital advancement and remodelling is an effective procedure for the correction of craniosynostosis, however, individual cases may require other procedures like total calvarial remodelling. (author)

  1. Porous hybrid structures based on P(DLLA-co-TMC) and collagen for tissue engineering of small-diameter blood vessels

    NARCIS (Netherlands)

    Buttafoco, L.; Boks, Niels P.; Engbers-Buijtenhuijs, P.; Grijpma, Dirk W.; Poot, Andreas A.; Dijkstra, Pieter J.; Vermes, I.; Feijen, Jan

    2006-01-01

    Poly (D,L-lactide)-7co-(1,3-trimethylene carbonate) [P(DLLA-co-TMC)] (83 mol % DLLA) was used to produce matrices suitable for tissue engineering of small-diameter blood vessels. The copolymer was processed into tubular structures with a porosity of 98% by melt spinning and fiber winding, thus

  2. Masked hypertension and cardiac remodeling in middle-aged endurance athletes

    OpenAIRE

    Trachsel, Lukas; Carlen, Frederic; Brugger, Nicolas Jacques; Seiler, Christian; Wilhelm, Matthias

    2015-01-01

    OBJECTIVES: Extensive endurance training and arterial hypertension are established risk factors for atrial fibrillation. We aimed to assess the proportion of masked hypertension in endurance athletes and the impact on cardiac remodeling, mechanics, and supraventricular tachycardias (SVT). METHODS: Male participants of a 10-mile race were recruited and included if office blood pressure was normal (

  3. Preintervention lesion remodelling affects operative mechanisms of balloon optimised directional coronary atherectomy procedures: a volumetric study with three dimensional intravascular ultrasound

    Science.gov (United States)

    von Birgelen, C; Mintz, G; de Vrey, E A; Serruys, P; Kimura, T; Nobuyoshi, M; Popma, J; Leon, M; Erbel, R; de Feyter, P J

    2000-01-01

    AIMS—To classify atherosclerotic coronary lesions on the basis of adequate or inadequate compensatory vascular enlargement, and to examine changes in lumen, plaque, and vessel volumes during balloon optimised directional coronary atherectomy procedures in relation to the state of adaptive remodelling before the intervention.
DESIGN—29 lesion segments in 29 patients were examined with intravascular ultrasound before and after successful balloon optimised directional coronary atherectomy procedures, and a validated volumetric intravascular ultrasound analysis was performed off-line to assess the atherosclerotic lesion remodelling and changes in plaque and vessel volumes that occurred during the intervention. Based on the intravascular ultrasound data, lesions were classified according to whether there was inadequate (group I) or adequate (group II) compensatory enlargement.
RESULTS—There was no significant difference in patient and lesion characteristics between groups I and II (n = 10 and 19), including lesion length and details of the intervention. Quantitative coronary angiographic data were similar for both groups. However, plaque and vessel volumes were significantly smaller in group I than in II. In group I, 9 (4)% (mean (SD)) of the plaque volume was ablated, while in group II 16 (11)% was ablated (p = 0.01). This difference was reflected in a lower lumen volume gain in group I than in group II (46 (18) mm3 v 80 (49) mm3 (p atherectomy procedures. Plaque ablation was found to be particularly low in lesions with inadequate compensatory vascular enlargement.


Keywords: intravascular ultrasound; ultrasonics; remodelling; coronary artery disease; atherectomy PMID:10648496

  4. 3-D trajectory model for MDT using micro-spheres implanted within large blood vessels

    Science.gov (United States)

    Choomphon-anomakhun, Natthaphon; Natenapit, Mayuree

    2016-09-01

    Implant assisted magnetic drug targeting (IA-MDT) using ferromagnetic spherical targets implanted within large blood vessels and subjected to a uniform externally applied magnetic field (H0) has been investigated and reported for the first time. The capture areas (As) of magnetic drug carrier particles (MDCPs) were determined from the analysis of particle trajectories simulated from equations of motion. Then, the effects of various parameters, such as types of ferromagnetic materials in the targets and MDCPs, blood flow rates, mass fraction of the ferromagnetic material in the MDCPs, average radii of MDCPs (Rp) and the strength of H0 on the As were obtained. Furthermore, the effects of saturation magnetization of the ferromagnetic materials in the MDCPs and within the targets on the As were analyzed. After this, the suitable strengths of H0 and Rp for IA-MDT designs were reported. Dimensionless As, ranging from 2 to 7, was obtained with Rp ranging from 500 to 2500 nm, μ0H0 less than 0.8 T and a blood flow rate of 0.1 m s-1. The target-MDCP materials considered are iron-iron, iron-magnetite and SS409-magnetite, respectively.

  5. Vascular remodeling versus amyloid beta-induced oxidative stress in the cerebrovascular dysfunctions associated with Alzheimer's disease.

    Science.gov (United States)

    Tong, Xin-Kang; Nicolakakis, Nektaria; Kocharyan, Ara; Hamel, Edith

    2005-11-30

    The roles of oxidative stress and structural alterations in the cerebrovascular dysfunctions associated with Alzheimer's disease (AD) were investigated in transgenic mice overexpressing amyloid precusor protein (APP+) or transforming growth factor-beta1 (TGF+). Age-related impairments and their in vitro reversibility were evaluated, and underlying pathogenic mechanisms were assessed and compared with those seen in AD brains. Vasoconstrictions to 5-HT and endothelin-1 were preserved, except in the oldest (18-21 months of age) TGF+ mice. Despite unaltered relaxations to sodium nitroprusside, acetylcholine (ACh) and calcitonin gene-related peptide-mediated dilatations were impaired, and there was an age-related deficit in the basal availability of nitric oxide (NO) that progressed more gradually in TGF+ mice. The expression and progression of these deficits were unrelated to the onset or extent of thioflavin-S-positive vessels. Manganese superoxide dismutase (SOD2) was upregulated in pial vessels and around brain microvessels of APP+ mice, pointing to a role of superoxide in the dysfunctions elicited by amyloidosis. In contrast, vascular wall remodeling associated with decreased levels of endothelial NO synthase and cyclooxygenase-2 and increased contents of vascular endothelial growth factor and collagen-I and -IV characterized TGF+ mice. Exogenous SOD or catalase normalized ACh dilatations and NO availability in vessels from aged APP+ mice but had no effect in those of TGF+ mice. Increased perivascular oxidative stress was not evidenced in AD brains, but vascular wall alterations compared well with those seen in TGF+ mice. We conclude that brain vessel remodeling and associated alterations in levels of vasoactive signaling molecules are key contributors to AD cerebrovascular dysfunctions.

  6. Melatonin Decreases Pulmonary Vascular Remodeling and Oxygen Sensitivity in Pulmonary Hypertensive Newborn Lambs

    Directory of Open Access Journals (Sweden)

    Cristian R. Astorga

    2018-03-01

    Full Text Available Background: Chronic hypoxia and oxidative stress during gestation lead to pulmonary hypertension of the neonate (PHN, a condition characterized by abnormal pulmonary arterial reactivity and remodeling. Melatonin has strong antioxidant properties and improves pulmonary vascular function. Here, we aimed to study the effects of melatonin on the function and structure of pulmonary arteries from PHN lambs.Methods: Twelve lambs (Ovis aries gestated and born at highlands (3,600 m were instrumented with systemic and pulmonary catheters. Six of them were assigned to the control group (CN, oral vehicle and 6 were treated with melatonin (MN, 1 mg.kg−1.d−1 during 10 days. At the end of treatment, we performed a graded oxygenation protocol to assess cardiopulmonary responses to inspired oxygen variations. Further, we obtained lung and pulmonary trunk samples for histology, molecular biology, and immunohistochemistry determinations.Results: Melatonin reduced the in vivo pulmonary pressor response to oxygenation changes. In addition, melatonin decreased cellular density of the media and diminished the proliferation marker KI67 in resistance vessels and pulmonary trunk (p < 0.05. This was associated with a decreased in the remodeling markers α-actin (CN 1.28 ± 0.18 vs. MN 0.77 ± 0.04, p < 0.05 and smoothelin-B (CN 2.13 ± 0.31 vs. MN 0.88 ± 0.27, p < 0.05. Further, melatonin increased vascular density by 134% and vascular luminal surface by 173% (p < 0.05. Finally, melatonin decreased nitrotyrosine, an oxidative stress marker, in small pulmonary vessels (CN 5.12 ± 0.84 vs. MN 1.14 ± 0.34, p < 0.05.Conclusion: Postnatal administration of melatonin blunts the cardiopulmonary response to hypoxia, reduces the pathological vascular remodeling, and increases angiogenesis in pulmonary hypertensive neonatal lambs.These effects improve the pulmonary vascular structure and function in the neonatal period under chronic hypoxia.

  7. Melatonin Decreases Pulmonary Vascular Remodeling and Oxygen Sensitivity in Pulmonary Hypertensive Newborn Lambs

    Science.gov (United States)

    Astorga, Cristian R.; González-Candia, Alejandro; Candia, Alejandro A.; Figueroa, Esteban G.; Cañas, Daniel; Ebensperger, Germán; Reyes, Roberto V.; Llanos, Aníbal J.; Herrera, Emilio A.

    2018-01-01

    Background: Chronic hypoxia and oxidative stress during gestation lead to pulmonary hypertension of the neonate (PHN), a condition characterized by abnormal pulmonary arterial reactivity and remodeling. Melatonin has strong antioxidant properties and improves pulmonary vascular function. Here, we aimed to study the effects of melatonin on the function and structure of pulmonary arteries from PHN lambs. Methods: Twelve lambs (Ovis aries) gestated and born at highlands (3,600 m) were instrumented with systemic and pulmonary catheters. Six of them were assigned to the control group (CN, oral vehicle) and 6 were treated with melatonin (MN, 1 mg.kg−1.d−1) during 10 days. At the end of treatment, we performed a graded oxygenation protocol to assess cardiopulmonary responses to inspired oxygen variations. Further, we obtained lung and pulmonary trunk samples for histology, molecular biology, and immunohistochemistry determinations. Results: Melatonin reduced the in vivo pulmonary pressor response to oxygenation changes. In addition, melatonin decreased cellular density of the media and diminished the proliferation marker KI67 in resistance vessels and pulmonary trunk (p < 0.05). This was associated with a decreased in the remodeling markers α-actin (CN 1.28 ± 0.18 vs. MN 0.77 ± 0.04, p < 0.05) and smoothelin-B (CN 2.13 ± 0.31 vs. MN 0.88 ± 0.27, p < 0.05). Further, melatonin increased vascular density by 134% and vascular luminal surface by 173% (p < 0.05). Finally, melatonin decreased nitrotyrosine, an oxidative stress marker, in small pulmonary vessels (CN 5.12 ± 0.84 vs. MN 1.14 ± 0.34, p < 0.05). Conclusion: Postnatal administration of melatonin blunts the cardiopulmonary response to hypoxia, reduces the pathological vascular remodeling, and increases angiogenesis in pulmonary hypertensive neonatal lambs.These effects improve the pulmonary vascular structure and function in the neonatal period under chronic hypoxia. PMID:29559926

  8. In-vivo imaging of blood flow in human retinal vessels using color Doppler optical coherence tomography

    Science.gov (United States)

    Yazdanfar, Siavash; Rollins, Andrew M.; Izatt, Joseph A.

    1999-04-01

    Quantification of retinal blood flow may lead to a better understanding of the progression and treatment of several ocular disorders, including diabetic retinopathy, age- related macular degeneration, and glaucoma. Current techniques, such as fluorescein angiography and laser Doppler velocimetry are limited, failing to provide sufficient information to the clinician. Color Doppler optical coherence tomography (CDOCT) is a novel technique using coherent heterodyne detection for simultaneous cross- sectional imaging of tissue microstructure and blood flow. This technique is capable of high spatial and velocity resolution imaging in highly scattering media. We implemented CDOCT for retinal blood flow mapping in human subjects. No dilation of the pupil was necessary. CDOCT is demonstrated for determining bidirectional flow in sub- 100micrometers diameter vessels in the retina. Additionally, we calculated Doppler broadening using the variance of depth- resolved spectra to identify regions with large velocity gradients within the Xenopus heart. This technique may be useful in quantifying local tissue perfusion in highly vascular retinal tissue.

  9. No-Regrets Remodeling, 2nd Edition

    Energy Technology Data Exchange (ETDEWEB)

    None

    2013-12-01

    No-Regrets Remodeling, sponsored by Oak Ridge National Laboratory, is an informative publication that walks homeowners and/or remodelers through various home remodeling projects. In addition to remodeling information, the publication provides instruction on how to incorporate energy efficiency into the remodeling process. The goal of the publication is to improve homeowner satisfaction after completing a remodeling project and to provide the homeowner with a home that saves energy and is comfortable and healthy.

  10. Association of various blood pressure variables and vascular phenotypes with coronary, stroke and renal deaths: Potential implications for prevention.

    Science.gov (United States)

    Harbaoui, Brahim; Courand, Pierre-Yves; Milon, Hughes; Fauvel, Jean-Pierre; Khettab, Fouad; Mechtouff, Laura; Cassar, Emmanuel; Girerd, Nicolas; Lantelme, Pierre

    2015-11-01

    The relationship between blood pressure (BP) and cardiovascular diseases has been extensively documented. However, the benefit of anti-hypertensive drugs differs according to the type of cardiovascular event. Aortic stiffness is tightly intertwined with BP and aorta cross-talk with small arteries. We endeavored to elucidate which BP component and type of vessel remodeling was predictive of the following outcomes: fatal myocardial infarction (MI), fatal stroke, renal -, coronary- or cerebrovascular-related deaths. Large vessel remodeling was estimated by an aortography-based aortic atherosclerosis score (ATS) while small vessel disease was documented by the presence of a hypertensive retinopathy. We included 1031 subjects referred for hypertension workup and assessed outcomes 30 years later. After adjustment for major risk factors, ATS and pulse pressure (PP) were predictive of coronary events while mean BP (MBP) and retinopathy were not. On the contrary, MBP was predictive of cerebrovascular and renal related deaths while ATS and PP were not. Retinopathy was only predictive of cerebrovascular related deaths. Lastly, the aortic atherosclerosis phenotype and increased PP identified patients prone to develop fatal MI whereas the retinopathy phenotype and increased MBP identified patients at higher risk of fatal stroke. These results illustrate the particular feature of the resistive coronary circulation comparatively to the brain and kidneys' low-resistance circulation. Our results advocate for a rational preventive strategy based on the identification of distinct clinical phenotypes. Accordingly, decreasing MBP levels could help preventing stroke in retinopathy phenotypes whereas targeting PP is possibly more efficient in preventing MI in atherosclerotic phenotypes. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. The FXR agonist PX20606 ameliorates portal hypertension by targeting vascular remodelling and sinusoidal dysfunction.

    Science.gov (United States)

    Schwabl, Philipp; Hambruch, Eva; Seeland, Berit A; Hayden, Hubert; Wagner, Michael; Garnys, Lukas; Strobel, Bastian; Schubert, Tim-Lukas; Riedl, Florian; Mitteregger, Dieter; Burnet, Michael; Starlinger, Patrick; Oberhuber, Georg; Deuschle, Ulrich; Rohr-Udilova, Nataliya; Podesser, Bruno K; Peck-Radosavljevic, Markus; Reiberger, Thomas; Kremoser, Claus; Trauner, Michael

    2017-04-01

    Steroidal farnesoid X receptor (FXR) agonists demonstrated potent anti-fibrotic activities and lowered portal hypertension in experimental models. The impact of the novel non-steroidal and selective FXR agonist PX20606 on portal hypertension and fibrosis was explored in this study. In experimental models of non-cirrhotic (partial portal vein ligation, PPVL, 7days) and cirrhotic (carbon tetrachloride, CCl 4 , 14weeks) portal hypertension, PX20606 (PX,10mg/kg) or the steroidal FXR agonist obeticholic acid (OCA,10mg/kg) were gavaged. We then measured portal pressure, intrahepatic vascular resistance, liver fibrosis and bacterial translocation. PX decreased portal pressure in non-cirrhotic PPVL (12.6±1.7 vs. 10.4±1.1mmHg; p=0.020) and cirrhotic CCl 4 (15.2±0.5 vs. 11.8±0.4mmHg; p=0.001) rats. In PPVL animals, we observed less bacterial translocation (-36%; p=0.041), a decrease in lipopolysaccharide binding protein (-30%; p=0.024) and splanchnic tumour necrosis factor α levels (-39%; p=0.044) after PX treatment. In CCl 4 rats, PX decreased fibrotic Sirius Red area (-43%; p=0.005), hepatic hydroxyproline (-66%; pportal pressure (-14%; p=0.041) by restoring endothelial function, 14week PX therapy additionally inhibited sinusoidal remodelling and decreased portal pressure to a greater extent (-22%; p=0.001). In human liver sinusoidal endothelial cells, PX increased eNOS and DDAH expression. The non-steroidal FXR agonist PX20606 ameliorates portal hypertension by reducing liver fibrosis, vascular remodelling and sinusoidal dysfunction. The novel drug PX20606 activates the bile acid receptor FXR and shows beneficial effects in experimental liver cirrhosis: In the liver, it reduces scarring and inflammation, and also widens blood vessels. Thus, PX20606 leads to an improved blood flow through the liver and decreases hypertension of the portal vein. Additionally, PX20606 improves the altered intestinal barrier and decreases bacterial migration from the gut. Copyright

  12. Antibody-linked drug destroys tumor cells and tumor blood vessels in many types of cancer | Center for Cancer Research

    Science.gov (United States)

    A team led by Brad St. Croix, Ph.D., Senior Associate Scientist, Mouse Cancer Genetics Program, has developed an antibody-drug conjugate (ADC) that destroys both tumor cells and the blood vessels that nourish them. The drug significantly shrank breast tumors, colon tumors and several other types of cancer and prolonged survival. Learn more...  

  13. Vessel calibre and haemoglobin effects on pulse oximetry

    International Nuclear Information System (INIS)

    McEwen, M P; Reynolds, K J; Bull, G P

    2009-01-01

    Despite its success as a clinical monitoring tool, pulse oximetry may be improved with respect to the need for empirical calibration and the reports of biases in readings associated with peripheral vasoconstriction and haemoglobin concentration. To effect this improvement, this work aims to improve the understanding of the photoplethysmography signal—as used by pulse oximeters—and investigates the effect of vessel calibre and haemoglobin concentration on pulse oximetry. The digital temperature and the transmission of a wide spectrum of light through the fingers of 57 people with known haemoglobin concentrations were measured and simulations of the transmission of that spectrum of light through finger models were performed. Ratios of pulsatile attenuations of light as used in pulse oximetry were dependent upon peripheral temperature and on blood haemoglobin concentration. In addition, both the simulation and in vivo results showed that the pulsatile attenuation of light through fingers was approximately proportional to the absorption coefficients of blood, only when the absorption coefficients were small. These findings were explained in terms of discrete blood vessels acting as barriers to light transmission through tissue. Due to the influence of discrete blood vessels on light transmission, pulse oximeter outputs tend to be dependent upon haemoglobin concentration and on the calibre of pulsing blood vessels—which are affected by vasoconstriction/vasodilation. The effects of discrete blood vessels may account for part of the difference between the Beer–Lambert pulse oximetry model and empirical calibration

  14. Microvascular Remodeling and Wound Healing: A Role for Pericytes

    Science.gov (United States)

    Dulmovits, Brian M.; Herman, Ira M.

    2012-01-01

    Physiologic wound healing is highly dependent on the coordinated functions of vascular and non-vascular cells. Resolution of tissue injury involves coagulation, inflammation, formation of granulation tissue, remodeling and scarring. Angiogenesis, the growth of microvessels the size of capillaries, is crucial for these processes, delivering blood-borne cells, nutrients and oxygen to actively remodeling areas. Central to angiogenic induction and regulation is microvascular remodeling, which is dependent upon capillary endothelial cell and pericyte interactions. Despite our growing knowledge of pericyte-endothelial cell crosstalk, it is unclear how the interplay among pericytes, inflammatory cells, glia and connective tissue elements shape microvascular injury response. Here, we consider the relationships that pericytes form with the cellular effectors of healing in normal and diabetic environments, including repair following injury and vascular complications of diabetes, such as diabetic macular edema and proliferative diabetic retinopathy. In addition, pericytes and stem cells possessing “pericyte-like” characteristics are gaining considerable attention in experimental and clinical efforts aimed at promoting healing or eradicating ocular vascular proliferative disorders. As the origin, identification and characterization of microvascular pericyte progenitor populations remains somewhat ambiguous, the molecular markers, structural and functional characteristics of pericytes will be briefly reviewed. PMID:22750474

  15. A new Python library to analyse skeleton images confirms malaria parasite remodelling of the red blood cell membrane skeleton

    Directory of Open Access Journals (Sweden)

    Juan Nunez-Iglesias

    2018-02-01

    Full Text Available We present Skan (Skeleton analysis, a Python library for the analysis of the skeleton structures of objects. It was inspired by the “analyse skeletons” plugin for the Fiji image analysis software, but its extensive Application Programming Interface (API allows users to examine and manipulate any intermediate data structures produced during the analysis. Further, its use of common Python data structures such as SciPy sparse matrices and pandas data frames opens the results to analysis within the extensive ecosystem of scientific libraries available in Python. We demonstrate the validity of Skan’s measurements by comparing its output to the established Analyze Skeletons Fiji plugin, and, with a new scanning electron microscopy (SEM-based method, we confirm that the malaria parasite Plasmodium falciparum remodels the host red blood cell cytoskeleton, increasing the average distance between spectrin-actin junctions.

  16. A new Python library to analyse skeleton images confirms malaria parasite remodelling of the red blood cell membrane skeleton.

    Science.gov (United States)

    Nunez-Iglesias, Juan; Blanch, Adam J; Looker, Oliver; Dixon, Matthew W; Tilley, Leann

    2018-01-01

    We present Skan (Skeleton analysis), a Python library for the analysis of the skeleton structures of objects. It was inspired by the "analyse skeletons" plugin for the Fiji image analysis software, but its extensive Application Programming Interface (API) allows users to examine and manipulate any intermediate data structures produced during the analysis. Further, its use of common Python data structures such as SciPy sparse matrices and pandas data frames opens the results to analysis within the extensive ecosystem of scientific libraries available in Python. We demonstrate the validity of Skan's measurements by comparing its output to the established Analyze Skeletons Fiji plugin, and, with a new scanning electron microscopy (SEM)-based method, we confirm that the malaria parasite Plasmodium falciparum remodels the host red blood cell cytoskeleton, increasing the average distance between spectrin-actin junctions.

  17. Large vessel involvement by IgG4-related disease

    Science.gov (United States)

    Perugino, Cory A.; Wallace, Zachary S.; Meyersohn, Nandini; Oliveira, George; Stone, James R.; Stone, John H.

    2016-01-01

    Abstract Objectives: IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition that can affect multiple organs and lead to tumefactive, tissue-destructive lesions. Reports have described inflammatory aortitis and periaortitis, the latter in the setting of retroperitoneal fibrosis (RPF), but have not distinguished adequately between these 2 manifestations. The frequency, radiologic features, and response of vascular complications to B cell depletion remain poorly defined. We describe the clinical features, radiology findings, and treatment response in a cohort of 36 patients with IgG4-RD affecting large blood vessels. Methods: Clinical records of all patients diagnosed with IgG4-RD in our center were reviewed. All radiologic studies were reviewed. We distinguished between primary large blood vessel inflammation and secondary vascular involvement. Primary involvement was defined as inflammation in the blood vessel wall as a principal focus of disease. Secondary vascular involvement was defined as disease caused by the effects of adjacent inflammation on the blood vessel wall. Results: Of the 160 IgG4-RD patients in this cohort, 36 (22.5%) had large-vessel involvement. The mean age at disease onset of the patients with large-vessel IgG4-RD was 54.6 years. Twenty-eight patients (78%) were male and 8 (22%) were female. Thirteen patients (36%) had primary IgG4-related vasculitis and aortitis with aneurysm formation comprised the most common manifestation. This affected 5.6% of the entire IgG4-RD cohort and was observed in the thoracic aorta in 8 patients, the abdominal aorta in 4, and both the thoracic and abdominal aorta in 3. Three of these aneurysms were complicated by aortic dissection or contained perforation. Periaortitis secondary to RPF accounted for 27 of 29 patients (93%) of secondary vascular involvement by IgG4-RD. Only 5 patients demonstrated evidence of both primary and secondary blood vessel involvement. Of those treated with

  18. Vitamin K2 Ameliorates Damage of Blood Vessels by Glucocorticoid: a Potential Mechanism for Its Protective Effects in Glucocorticoid-induced Osteonecrosis of the Femoral Head in a Rat Model.

    Science.gov (United States)

    Zhang, Yuelei; Yin, Junhui; Ding, Hao; Zhang, Changqing; Gao, You-Shui

    2016-01-01

    Glucocorticoid has been reported to decrease blood vessel number and harm the blood supply in the femoral head, which is recognized to be an important mechanism of glucocorticoid-induced osteonecrosis of the femoral head (ONFH). To prevent glucocorticoid-induced ONFH, medication that promotes both bone formation and angiogenesis would be ideal. Vitamin K2 has been revealed to play an important role in bone metabolism; however, few studies have focused on the effect of Vitamin K2 on new vascular formation. Thus, this study aimed to investigate whether Vitamin K2 promoted new blood vessel formation in the presence of glucocorticoids, both in vitro and in vivo. The effect of Vitamin K2 on viability, migration, in vitro tube formation, and VEGF, vWF, CD31, KDR, Flt and PDGFB in EAhy926 incubated with or without dexamethasone were elucidated. VEGF, TGF-β and BMP-2, angiogenesis-related proteins secreted by osteoblasts, were also detected in the osteoblast-like cell line of MG63. In addition, blood vessels of the femoral head in rats administered with or without methylprednisolone and Vitamin K2 were evaluated using angiography and CD31 staining. In vitro studies showed that Vitamin K2 significantly protected endothelial cells from dexamethasone-induced apoptosis, promoted endothelial cell migration and in vitro tube formation. Angiogenesis-related proteins both in EAhy926 and MG63 were also upregulated by Vitamin K2 when cotreated with dexamethasone. In vivo studies showed enhanced blood vessel volume and CD31-positive staining cells in rats cotreated with VK2 and methylprednisolone compared to rats treated with methylprednisolone only. Collectively, Vitamin K2 has the ability to promote angiogenesis in vitro and to ameliorate vessels of the femoral head in glucocorticoid-treated rats in vivo, indicating that Vitamin K2 is a promising drug that may be used to prevent steroid-induced ONFH.

  19. An integrated 3-D image of cerebral blood vessels and CT view of tumor

    International Nuclear Information System (INIS)

    Suetens, P.; Baert, A.L.; Gybels, J.; Haegemans, S.; Jansen, P.; Oosterlinck, A.; Wilms, G.

    1984-01-01

    The authors developed a method that yields an integrated three-dimensional image of cerebral blood vessels and CT view of tumor. This method allows the neurosurgeon to choose any electrode trajectory that looks convenient to him, without imminent danger of causing a hemorrhage. Besides offering more safety to stereotactic interventions, this integrated 3-D image also has other applications. First, it gives a better characterization of most focal mass lesions seen by CT. Second, it allows high dose focal irradiation to be effected in such a way as to avoid arteries and veins. Third, it provides useful information for planning the strategy of open surgery

  20. Automated classification and quantitative analysis of arterial and venous vessels in fundus images

    Science.gov (United States)

    Alam, Minhaj; Son, Taeyoon; Toslak, Devrim; Lim, Jennifer I.; Yao, Xincheng

    2018-02-01

    It is known that retinopathies may affect arteries and veins differently. Therefore, reliable differentiation of arteries and veins is essential for computer-aided analysis of fundus images. The purpose of this study is to validate one automated method for robust classification of arteries and veins (A-V) in digital fundus images. We combine optical density ratio (ODR) analysis and blood vessel tracking algorithm to classify arteries and veins. A matched filtering method is used to enhance retinal blood vessels. Bottom hat filtering and global thresholding are used to segment the vessel and skeleton individual blood vessels. The vessel tracking algorithm is used to locate the optic disk and to identify source nodes of blood vessels in optic disk area. Each node can be identified as vein or artery using ODR information. Using the source nodes as starting point, the whole vessel trace is then tracked and classified as vein or artery using vessel curvature and angle information. 50 color fundus images from diabetic retinopathy patients were used to test the algorithm. Sensitivity, specificity, and accuracy metrics were measured to assess the validity of the proposed classification method compared to ground truths created by two independent observers. The algorithm demonstrated 97.52% accuracy in identifying blood vessels as vein or artery. A quantitative analysis upon A-V classification showed that average A-V ratio of width for NPDR subjects with hypertension decreased significantly (43.13%).

  1. Chromatin Remodeling and Plant Immunity.

    Science.gov (United States)

    Chen, W; Zhu, Q; Liu, Y; Zhang, Q

    Chromatin remodeling, an important facet of the regulation of gene expression in eukaryotes, is performed by two major types of multisubunit complexes, covalent histone- or DNA-modifying complexes, and ATP-dependent chromosome remodeling complexes. Snf2 family DNA-dependent ATPases constitute the catalytic subunits of ATP-dependent chromosome remodeling complexes, which accounts for energy supply during chromatin remodeling. Increasing evidence indicates a critical role of chromatin remodeling in the establishment of long-lasting, even transgenerational immune memory in plants, which is supported by the findings that DNA methylation, histone deacetylation, and histone methylation can prime the promoters of immune-related genes required for disease defense. So what are the links between Snf2-mediated ATP-dependent chromosome remodeling and plant immunity, and what mechanisms might support its involvement in disease resistance? © 2017 Elsevier Inc. All rights reserved.

  2. Granulocytes and vascularization regulate uterine bleeding and tissue remodeling in a mouse menstruation model.

    Directory of Open Access Journals (Sweden)

    Astrid Menning

    Full Text Available Menstruation-associated disorders negatively interfere with the quality of life of many women. However, mechanisms underlying pathogenesis of menstrual disorders remain poorly investigated up to date. Among others, this is based on a lack of appropriate pre-clinical animal models. We here employ a mouse menstruation model induced by priming mice with gonadal hormones and application of a physical stimulus into the uterus followed by progesterone removal. As in women, these events are accompanied by menstrual-like bleeding and tissue remodeling processes, i.e. disintegration of decidualized endometrium, as well as subsequent repair. We demonstrate that the onset of bleeding coincides with strong upregulation of inflammatory mediators and massive granulocyte influx into the uterus. Uterine granulocytes play a central role in regulating local tissue remodeling since depletion of these cells results in dysregulated expression of matrix modifying enzymes. As described here for the first time, uterine blood loss can be quantified by help of tampon-like cotton pads. Using this novel technique, we reveal that blood loss is strongly reduced upon inhibition of endometrial vascularization and thus, is a key regulator of menstrual bleeding. Taken together, we here identify angiogenesis and infiltrating granulocytes as critical determinants of uterine bleeding and tissue remodeling in a mouse menstruation model. Importantly, our study provides a technical and scientific basis allowing quantification of uterine blood loss in mice and thus, assessment of therapeutic intervention, proving great potential for future use in basic research and drug discovery.

  3. Tubular inverse opal scaffolds for biomimetic vessels

    Science.gov (United States)

    Zhao, Ze; Wang, Jie; Lu, Jie; Yu, Yunru; Fu, Fanfan; Wang, Huan; Liu, Yuxiao; Zhao, Yuanjin; Gu, Zhongze

    2016-07-01

    There is a clinical need for tissue-engineered blood vessels that can be used to replace or bypass damaged arteries. The success of such grafts depends strongly on their ability to mimic native arteries; however, currently available artificial vessels are restricted by their complex processing, controversial integrity, or uncontrollable cell location and orientation. Here, we present new tubular scaffolds with specific surface microstructures for structural vessel mimicry. The tubular scaffolds are fabricated by rotationally expanding three-dimensional tubular inverse opals that are replicated from colloidal crystal templates in capillaries. Because of the ordered porous structure of the inverse opals, the expanded tubular scaffolds are imparted with circumferentially oriented elliptical pattern microstructures on their surfaces. It is demonstrated that these tailored tubular scaffolds can effectively make endothelial cells to form an integrated hollow tubular structure on their inner surface and induce smooth muscle cells to form a circumferential orientation on their outer surface. These features of our tubular scaffolds make them highly promising for the construction of biomimetic blood vessels.There is a clinical need for tissue-engineered blood vessels that can be used to replace or bypass damaged arteries. The success of such grafts depends strongly on their ability to mimic native arteries; however, currently available artificial vessels are restricted by their complex processing, controversial integrity, or uncontrollable cell location and orientation. Here, we present new tubular scaffolds with specific surface microstructures for structural vessel mimicry. The tubular scaffolds are fabricated by rotationally expanding three-dimensional tubular inverse opals that are replicated from colloidal crystal templates in capillaries. Because of the ordered porous structure of the inverse opals, the expanded tubular scaffolds are imparted with circumferentially

  4. About a mechanism of the influence of shear stress for viscosity of the blood in vessels of small diameter

    Directory of Open Access Journals (Sweden)

    Лев Николаевич Катюхин

    2014-12-01

    Full Text Available It is proposed a physiological and experimentally confirmed explanation of Fåhraeus-Lindqvist-effect in capillaries using the profile analyses of osmotic deformability of red blood cells. It was shown the dose-dependent change of the erythrocytes deformability in the stage of isotropic spheres after forming artificial water pores (nystatin and occlusion (PbCl2 of available pores. The Sigma-effect reducing of hematocrit and viscosity in a shear flow of blood through the vessels of a small diameter was conditioned by the interchange of liquid phase between the erythrocyte and the plasma.

  5. Infrared tomography for diagnostic imaging of port wine stain blood vessels

    Energy Technology Data Exchange (ETDEWEB)

    Goodman, D. [Lawrence Livermore National Lab., CA (United States)

    1994-11-15

    The objective of this work is the development of Infrared Tomography (IRT) for detecting and characterizing subsurface chromophores in human skin. Characterization of cutaneous chromophores is crucial for advances in the laser treatment of pigmented lesions (e.g., port wine stain birthmarks and tatoos). Infrared tomography (IRT) uses a fast infrared focal plane array (IR-FPA) to detect temperature rises in a substrate induced by pulsed radiation. A pulsed laser is used to produce transient heating of an object. The temperature rise, due to the optical absorption of the pulsed laser light, creates an increase in infrared emission which is measured by the IR-FPA. Although the application of IRT to image subsurface cracks due to metal fatigue is a topic of great interest in the aircraft industry, the application to image subsurface chromophores in biological materials is novel. We present an image recovery method based on a constrained conjugate gradient algorithm that has obtained the first ever high quality images of port wine blood vessels.

  6. Insulin-like Growth Factor 1 (IGF-1) Stabilizes Nascent Blood Vessels*

    Science.gov (United States)

    Jacobo, Sarah Melissa P.; Kazlauskas, Andrius

    2015-01-01

    Here we report that VEGF-A and IGF-1 differ in their ability to stabilize newly formed blood vessels and endothelial cell tubes. Although VEGF-A failed to support an enduring vascular response, IGF-1 stabilized neovessels generated from primary endothelial cells derived from various vascular beds and mouse retinal explants. In these experimental systems, destabilization/regression was driven by lysophosphatidic acid (LPA). Because previous studies have established that Erk antagonizes LPA-mediated regression, we considered whether Erk was an essential component of IGF-dependent stabilization. Indeed, IGF-1 lost its ability to stabilize neovessels when the Erk pathway was inhibited pharmacologically. Furthermore, stabilization was associated with prolonged Erk activity. In the presence of IGF-1, Erk activity persisted longer than in the presence of VEGF or LPA alone. These studies reveal that VEGF and IGF-1 can have distinct inputs in the angiogenic process. In contrast to VEGF, IGF-1 stabilizes neovessels, which is dependent on Erk activity and associated with prolonged activation. PMID:25564613

  7. Quantitative ex-vivo micro-computed tomographic imaging of blood vessels and necrotic regions within tumors.

    Science.gov (United States)

    Downey, Charlene M; Singla, Arvind K; Villemaire, Michelle L; Buie, Helen R; Boyd, Steven K; Jirik, Frank R

    2012-01-01

    Techniques for visualizing and quantifying the microvasculature of tumors are essential not only for studying angiogenic processes but also for monitoring the effects of anti-angiogenic treatments. Given the relatively limited information that can be gleaned from conventional 2-D histological analyses, there has been considerable interest in methods that enable the 3-D assessment of the vasculature. To this end, we employed a polymerizing intravascular contrast medium (Microfil) and micro-computed tomography (micro-CT) in combination with a maximal spheres direct 3-D analysis method to visualize and quantify ex-vivo vessel structural features, and to define regions of hypoperfusion within tumors that would be indicative of necrosis. Employing these techniques we quantified the effects of a vascular disrupting agent on the tumor vasculature. The methods described herein for quantifying whole tumor vascularity represent a significant advance in the 3-D study of tumor angiogenesis and evaluation of novel therapeutics, and will also find potential application in other fields where quantification of blood vessel structure and necrosis are important outcome parameters.

  8. Pericyte coverage of abnormal blood vessels in myelofibrotic bone marrows

    DEFF Research Database (Denmark)

    Zetterberg, Eva; Vannucchi, Alessandro M; Migliaccio, Anna Rita

    2007-01-01

    BACKGROUND AND OBJECTIVES: Myelofibrotic bone marrow displays abnormal angiogenesis but the pathogenic mechanisms of this are poorly understood. Since pericyte abnormalities are described on solid tumor vessels we studied whether vessel morphology and pericyte coverage in bone marrow samples from...

  9. [Aetiology and pathogenesis of damages to blood vessels in drug addicts].

    Science.gov (United States)

    Sultanaliev, T A; Tursynbaev, S E; Ivakin, V M

    2007-01-01

    The article deals with the problems concerning aetiology and pathogenesis of damages to blood vessels in patients practicing parenteral administration of surrogates of narcotic substances. In order to clinically and experimentally study the pattern of morphological alterations in the area of narcotic substances administration and to work out an appropriate classification of the forms and stages of development of the pathological process, the authors analysed the clinical course of vascular lesions and complications thereof in a total of 244 drug abusers having parenterally administered surrogates of narcotic substances and undergoing treatment at the Department of Vascular Surgery of the Municipal Clinical Hospital of the city of Almaty. Additionally, experimental studies were carried out on 16 rabbits with the induced model of parenteral administration of surrogates of narcotic substances, thus making it possible to study the degree of their effect and to confirm the theory of a chemical impact of the homemade drugs on the vascular wall. The findings of the carried out studies enabled us to single out the following clinical stages of vascular lesions: stage I - the initial stage of cicatricial-and-ulcerous lesions formation, stage II - formation of cutaneous-and-vascular fistulas, stage III - the stage of complications characterized by development of health-hazardous vascular lesions, i. e., arterial and venous thromboses of the major vessels, as well as arrosive bleedings. It was noted that more than 50% of patients were admitted to the clinic presenting with the third stage of vascular lesions. The experimental part of the study included 64 experiments on 16 rabbits (one experiment per each paw of the animal). The laboratory animals were subdivided into three groups. The first experimental group consisted of the rabbits with a mechanically inflicted injury to the vessels. The second and third experimental groups were composed of the rabbits having received

  10. Blood vessels in subcaruncular and intercaruncular bovine endometriun possess oxytocin receptors (ORT) and express otr mRNA during pregnancy

    DEFF Research Database (Denmark)

    Fuchs, Anna-Ritta; Balvers, Marga; Ivell, Richard

    2002-01-01

    is taking place; marked changes were observed with advancing pregnancy. The epithelial cells of the trophoblast were strongly stained for ir OTR and OTR mRNA, as reported last year, but the fetal connective tissue and blood vessels within the trophoblast did not show any stain for ir OTR or OTR m...... placentation because episodic secretion of OT occurs throughout bovine pregnancy...

  11. A method for increasing the homogeneity of the temperature distribution during magnetic fluid hyperthermia with a Fe-Cr-Nb-B alloy in the presence of blood vessels

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Yundong [College of Physics and Information Engineering, Fuzhou University, Fuzhou 350116 (China); Flesch, Rodolfo C.C. [Departamento de Automação e Sistemas, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC (Brazil); Jin, Tao, E-mail: jintly@fzu.edu.cn [College of Electrical Engineering and Automation, Fuzhou University, Fuzhou 350116 (China)

    2017-06-15

    Highlights: • The effects of blood vessels on temperature field distribution are investigated. • The critical thermal energy of hyperthermia is computed by the Finite Element Analysis. • A treatment method is proposed by using the MNPs with low Curie temperature. • The cooling effects due to the blood flow can be controlled. - Abstract: Magnetic hyperthermia ablates tumor cells by absorbing the thermal energy from magnetic nanoparticles (MNPs) under an external alternating magnetic field. The blood vessels (BVs) within tumor region can generally reduce treatment effectiveness due to the cooling effect of blood flow. This paper aims to investigate the cooling effect of BVs on the temperature field of malignant tumor regions using a complex geometric model and numerical simulation. For deriving the model, the Navier-Stokes equation for blood flow is combined with Pennes bio-heat transfer equation for human tissue. The effects on treatment temperature caused by two different BV distributions inside a mammary tumor are analyzed through numerical simulation under different conditions of flow rate considering a Fe-Cr-Nb-B alloy, which has low Curie temperature ranging from 42 °C to 45 °C. Numerical results show that the multi-vessel system has more obvious cooling effects than the single vessel one on the temperature field distribution for hyperthermia. Besides, simulation results show that the temperature field within tumor area can also be influenced by the velocity and diameter of BVs. To minimize the cooling effect, this article proposes a treatment method based on the increase of the thermal energy provided to MNPs associated with the adoption of low Curie temperature particles recently reported in literature. Results demonstrate that this approach noticeably improves the uniformity of the temperature field, and shortens the treatment time in a Fe-Cr-Nb-B system, thus reducing the side effects to the patient.

  12. Endothelial cell impact on smooth muscle cell properties: role of hemodynamic forces

    OpenAIRE

    Killeen, Maria T.

    2009-01-01

    The vascular endothelium is a dynamic cell monolayer located at the interface of the vessel wall and bloodstream, where it regulates the physiological effects of humoral and hemodynamic stimuli on vessel tone and remodelling. Hemodynamic forces are of particular interest and include shear stress, the frictional force generated by blood as it drags against the endothelium, and cyclic strain, transmural pressure due to the pulsatile nature of blood flow. Both forces can profoundly modulate vasc...

  13. Engineering blood vessels through micropatterned co-culture of vascular endothelial and smooth muscle cells on bilayered electrospun fibrous mats with pDNA inoculation.

    Science.gov (United States)

    Liu, Yaowen; Lu, Jinfu; Li, Huinan; Wei, Jiaojun; Li, Xiaohong

    2015-01-01

    Although engineered blood vessels have seen important advances during recent years, proper mechanical strength and vasoactivity remain unsolved problems. In the current study, micropatterned fibrous mats were created to load smooth muscle cells (SMC), and a co-culture with endothelial cells (EC) was established through overlaying on an EC-loaded flat fibrous mat to mimic the layered structure of a blood vessel. A preferential distribution of SMC was determined in the patterned regions throughout the fibrous scaffolds, and aligned fibers in the patterned regions provided topological cues to guide the orientation of SMC with intense actin filaments and extracellular matrix (ECM) production in a circumferential direction. Plasmid DNA encoding basic fibroblast growth factors and vascular endothelial growth factor were integrated into electrospun fibers as biological cues to promote SMC infiltration into fibrous mats, and the viability and ECM production of both EC and SMC. The layered fibrous mats with loaded EC and SMC were wrapped into a cylinder, and engineered vessels were obtained with compact EC and SMC layers after co-culture for 3 months. Randomly oriented ECM productions of EC formed a continuous endothelium covering the entire lumenal surface, and a high alignment of ECM was shown in the circumferential direction of SMC layers. The tensile strength, strain at failure and suture retention strength were higher than those of the human femoral artery, and the burst pressure and radial compliance were in the same range as the human saphenous vein, indicating potential as blood vessel substitutes for transplantation in vivo. Thus, the establishment of topographical cues and biochemical signals in fibrous scaffolds demonstrates advantages in modulating cellular behavior and organization found in complex multicellular tissues. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  14. Ultrasound sonication with microbubbles disrupts blood vessels and enhances tumor treatments of anticancer nanodrug

    Directory of Open Access Journals (Sweden)

    Lin CY

    2012-04-01

    Full Text Available Chung-Yin Lin1*, Hsiao-Ching Tseng1*, Heng-Ruei Shiu1, Ming-Fang Wu2, Cheng-Ying Chou3, Win-Li Lin1,41Institute of Biomedical Engineering, 2Laboratory Animal Center, 3Department of Bio-Industrial Mechatronics Engineering, National Taiwan University, Taipei, Taiwan; 4Division of Medical Engineering Research, National Health Research Institutes, Miaoli, Taiwan*These authors contributed equally to this workAbstract: Ultrasound (US sonication with microbubbles (MBs has the potential to disrupt blood vessels and enhance the delivery of drugs into the sonicated tissues. In this study, mouse ear tumors were employed to investigate the therapeutic effects of US, MBs, and pegylated liposomal doxorubicin (PLD on tumors. Tumors started to receive treatments when they grew up to about 15 mm3 (early stage with injection of PLD 10 mg/kg, or up to 50 mm3 (medium stage with PLD 6 (or 4 mg/kg. Experiments included the control, PLD alone, PLD + MBs + US, US alone, and MBs + US groups. The procedure for the PLD + MBs + US group was that PLD was injected first, MB (SonoVue injection followed, and then US was immediately sonicated on the tumor. The results showed that: (1 US sonication with MBs was always able to produce a further hindrance to tumor growth for both early and medium-stage tumors; (2 for the medium-stage tumors, 6 mg/kg PLD alone was able to inhibit their growth, while it did not work for 4 mg/kg PLD alone; (3 with the application of MBs + US, 4 mg/kg PLD was able to inhibit the growth of medium-stage tumors; (4 for early stage tumors after the first treatment with a high dose of PLD alone (10 mg/kg, the tumor size still increased for several days and then decreased (a biphasic pattern; (5 MBs + US alone was able to hinder the growth of early stage tumors, but unable to hinder that of medium stage tumors. The results of histological examinations and blood perfusion measurements indicated that the application of MBs + US disrupts the tumor blood

  15. Rapid analysis of vessel elements (RAVE: a tool for studying physiologic, pathologic and tumor angiogenesis.

    Directory of Open Access Journals (Sweden)

    Marc E Seaman

    Full Text Available Quantification of microvascular network structure is important in a myriad of emerging research fields including microvessel remodeling in response to ischemia and drug therapy, tumor angiogenesis, and retinopathy. To mitigate analyst-specific variation in measurements and to ensure that measurements represent actual changes in vessel network structure and morphology, a reliable and automatic tool for quantifying microvascular network architecture is needed. Moreover, an analysis tool capable of acquiring and processing large data sets will facilitate advanced computational analysis and simulation of microvascular growth and remodeling processes and enable more high throughput discovery. To this end, we have produced an automatic and rapid vessel detection and quantification system using a MATLAB graphical user interface (GUI that vastly reduces time spent on analysis and greatly increases repeatability. Analysis yields numerical measures of vessel volume fraction, vessel length density, fractal dimension (a measure of tortuosity, and radii of murine vascular networks. Because our GUI is open sourced to all, it can be easily modified to measure parameters such as percent coverage of non-endothelial cells, number of loops in a vascular bed, amount of perfusion and two-dimensional branch angle. Importantly, the GUI is compatible with standard fluorescent staining and imaging protocols, but also has utility analyzing brightfield vascular images, obtained, for example, in dorsal skinfold chambers. A manually measured image can be typically completed in 20 minutes to 1 hour. In stark comparison, using our GUI, image analysis time is reduced to around 1 minute. This drastic reduction in analysis time coupled with increased repeatability makes this tool valuable for all vessel research especially those requiring rapid and reproducible results, such as anti-angiogenic drug screening.

  16. Gain-of-function somatic mutations contribute to inflammation and blood vessel damage that lead to Alzheimer dementia: a hypothesis.

    Science.gov (United States)

    Marchesi, Vincent T

    2016-02-01

    Amyloid deposits are a characteristic feature of advanced Alzheimer dementia (AD), but whether they initiate the disease or are a consequence of it remains an unsettled question. To explore an alternative pathogenic mechanism, I propose that the triggering events that begin the pathogenic cascade are not amyloid deposits but damaged blood vessels caused by inflammatory reactions that lead to ischemia, amyloid accumulation, axonal degeneration, synaptic loss, and eventually irreversible neuronal cell death. Inflammation and blood vessel damage are well recognized complications of AD, but what causes them and why the cerebral microvasculature is affected have never been adequately addressed. Because heritable autosomal dominant mutations of NLRP3, APP, TREX1, NOTCH3, and Col4A1 are known to provoke inflammatory reactions and damage the brain in a wide variety of diseases, I propose that one or more low abundant, gain-of-function somatic mutations of the same 5 gene families damage the microvasculature of the brain that leads to dementia. This implies that the pathogenic triggers that lead to AD are derived not from external invaders or amyloid but from oxidative damage of our own genes. © FASEB.

  17. Effects of irradiation on renal vessels of rabbits

    International Nuclear Information System (INIS)

    Hanayama, Hirotaka

    1982-01-01

    The male rabbits weighing approximately 3 kg were divided into two groups: one group received irradiation to the left kidney through 6 x 4 cm field size with doses of 5 Gy, while the other group was irradiated with 50 Gy. The vessel casts were observed using the injection replica scanning electron microscopic method. In 50 Gy irradiated group, the surface of blood vessel's lumen became irregular with a decrease in the number of glomeruli at 5 days. Partial narrowing was also seen in the cortex and glomerular vessels. The number of glomeruli decreased by 48% one week later and 90% 4 weeks later. The cortex vessels progressively narrowed, and irregularity of the net-like structure was also observed. Similarly, a decrease in the number of glomeruli and partial narrowing of the blood vessels were seen at 5 days on the nonirradiated side, but the damage was considerably less than that on the irradiated side. In the 5 Gy irradiated group, a decrease in the number of glomeruli was seen 5 days later and it became 71% 5 days later and 81% one week later. It returned to 95% 4 weeks later. No changes whatsoever were seen in the non-irradiated side after 4 weeks and changes in the number of glomeruli were not observed. The vasculation of medulla showed no changes in the 50 Gy or the 5 Gy irradiated group. There were seen no significant changes in the blood vessel diameter. (J.P.N.)

  18. Chromatin Remodelers: From Function to Dysfunction

    Directory of Open Access Journals (Sweden)

    Gernot Längst

    2015-06-01

    Full Text Available Chromatin remodelers are key players in the regulation of chromatin accessibility and nucleosome positioning on the eukaryotic DNA, thereby essential for all DNA dependent biological processes. Thus, it is not surprising that upon of deregulation of those molecular machines healthy cells can turn into cancerous cells. Even though the remodeling enzymes are very abundant and a multitude of different enzymes and chromatin remodeling complexes exist in the cell, the particular remodeling complex with its specific nucleosome positioning features must be at the right place at the right time in order to ensure the proper regulation of the DNA dependent processes. To achieve this, chromatin remodeling complexes harbor protein domains that specifically read chromatin targeting signals, such as histone modifications, DNA sequence/structure, non-coding RNAs, histone variants or DNA bound interacting proteins. Recent studies reveal the interaction between non-coding RNAs and chromatin remodeling complexes showing importance of RNA in remodeling enzyme targeting, scaffolding and regulation. In this review, we summarize current understanding of chromatin remodeling enzyme targeting to chromatin and their role in cancer development.

  19. A kinematic study of pulsation in the dorsal blood vessel of the blackworm, Lumbriculus variegatus

    Directory of Open Access Journals (Sweden)

    Kameko Halfmann

    2011-01-01

    Full Text Available The aquatic oligochaete Lumbriculus variegatus has a segmented, dorsal blood vessel (DBV that acts as a peristaltic pump to move blood through the animal's closed circulatory system. We conducted a kinematic study using videography and computational modeling as a first step toward understanding the control of DBV pulsation. Results suggested that pulse rates were highest in the posterior segments, while interpulse intervals and intersegmental delays were longest in the midbody segments. Differences in the interpulse interval distributions across regions suggest that some peristaltic waves initiated in the posterior segments do not propagate all the way to the anterior segments. A simple model consisting of a chain of excitable neuromuscular units replicated these kinetics. This model may be useful in future research aimed at understanding the modulatory effect of biogenic amines on peristalsis of the DBV. Moreover, research into the mechanisms of peristalsis of the DBV may lead to insights into disorders of peristalsis in human and veterinary medicine

  20. Treatment of radiation exposure and regeneration medicine. Regeneration treatment of blood vessels by transplantation of autologous marrow monocytes

    International Nuclear Information System (INIS)

    Nagai, Kazuhiro; Kamihira, Shimeru; Matsumaru, Ichiro; Fukushima, Takuya; Yamaguchi, Hakuichiro; Miyazaki, Yasushi; Yamachika, Shiro; Eishi, Kiyoyuki; Tomonaga, Masao

    2007-01-01

    Described are usefulness and future view of regenerative medicine in the treatment of radiation exposure as exemplified by the vascular regeneration by autologous marrow cell transplantation. Vascular endothelial cells (VEC), possessing a high ability to divide, are known sensitive to radiation, which gives damage of blood vessel to alter its permeability leading to apoptosis of VEC, organ/tissue injuries and final damages in the cerebral blood vessels, central nervous system and skin, the acute radiation syndrome (ARS). Authors present successful cases of patients with chronic limb ischemia in the Therapeutic Angiogenesis using Cell Transplantation Trial (TACT), to whom the treatment is conducted with transplantation of autologous marrow monocyte fraction containing endothelial progenitor cells that differentiate to VEC. As well, they touch on a case of the patient encountered in a nuclear accident, mentioning that VEC are found partly derived from the donor after heamatopoietic stem cell transplantation (HSCT). Efficacy of HSCT in a literature is reviewed and commented to be an only limited one in 31 patients of various radiation accidents. However, treatment of ARS where stem cells are target, with regenerative medicine will become more useful in future, as basic and clinical researches will provide requisite findings. (T.I.)

  1. [Association between pulmonary vascular remodeling and expression of hypoxia-inducible factor-1α, endothelin-1 and inducible nitric oxide synthase in pulmonary vessels in neonatal rats with hypoxic pulmonary hypertension].

    Science.gov (United States)

    Wang, Jian-Rong; Zhou, Ying; Sang, Kui; Li, Ming-Xia

    2013-02-01

    To investigate the association between pulmonary vascular remodeling and expression of hypoxia-inducible factor-1α (HIF-1α), endothelin-1 (ET-1) and inducible nitric oxide synthase (iNOS) in pulmonary vessels in neonatal rats with hypoxic pulmonary hypertension (HPH). A neonatal rat model of HPH was established as an HPH group, and normal neonatal rats were enrolled as a control group. The mean pulmonary arterial pressure (mPAP) was measured. The percentage of medial thickness to outer diameter of the small pulmonary arteries (MT%) and the percentage of medial cross-section area to total cross-section area of the pulmonary small arteries (MA%) were measured as the indicators for pulmonary vascular remodeling. The immunohistochemical reaction intensities for HIF-1α, ET-1 and iNOS and their mRNA expression in lung tissues of neonatal rats were measured. Correlation analysis was performed to determine the relationship between pulmonary vascular remodeling and mRNA expression of HIF-1α, ET-1 and iNOS. The mPAP of the HPH group kept increasing on days 3, 5, 7, 10, 14, and 21 of hypoxia, with a significant difference compared with the control group (P<0.05). The HPH group had significantly higher MT% and MA% than the control group from day 7 of hypoxia (P<0.05). HIF-1α protein expression increased significantly on days 3, 5, 7 and 10 days of hypoxia, and HIF-1α mRNA expression increased significantly on days 3, 5 and 7 days of hypoxia in the HPH group compared with the control group (P<0.05). ET-1 protein expression increased significantly on days 3, 5 and 7 days of hypoxia and ET-1 mRNA expression increased significantly on day 3 of hypoxia in the HPH group compared with the control group (P<0.05). Both iNOS protein and mRNA expression were significantly higher on days 3, 5 and 7 days of hypoxia than the control group (P<0.05). Both MT% and MA% were positively correlated with HIF-1α mRNA expression (r=0.835 and 0.850 respectively; P<0.05). Pulmonary vascular

  2. [Hemodynamic phenomena in retrobulhar and eyeball vessels].

    Science.gov (United States)

    Modrzejewska, Monika

    2011-01-01

    The purpose of this review was to evaluate factors connected with blood flow and indices regulating vascular diameter and some parameters influencing retrobulbar circulation such as type of vascular resistance, anatomical structure of vascular wall and vessel lumen. Neurogenic and angiogenic factors, rheological blood composition, presence of anatomical and pathological obstructions on blood flow pathway as well as degree of development of collateral circulation pathways--have influence on the volume and blood flow velocity in eyeball. There were discussed bulbar circulation hemodynamics, emphasizing the importance of perfusion pressure. The role of risk factors was underlined for pathological lesions in vessels supplying blood to eyeball and in ophthalmic artery (OA) and its collaterals, in central retinal artery (CRA) as well as posterior ciliary arteries (PCAs), and in venous system carrying away blood from eye. IN CONCLUSION--the results of many studies of retrobulbar blood flow in different types of ophthalmic diseases of the vascular etiopathogenesis indicate that registry of the mean values of blood flow parameters and vascular resistance indices parallel to measurement of blood flow spectrum in OA, CRA, PCAs arteries, might contribute much information to explain or to evaluate nature of pathological changes in retinal and choroidal circulation.

  3. Krypton laser photocoagulation induces retinal vascular remodeling rather than choroidal neovascularization.

    Science.gov (United States)

    Behar-Cohen, F; Benezra, D; Soubrane, G; Jonet, L; Jeanny, J C

    2006-08-01

    photocoagulation site and around it. Confocal microscopy demonstrates that the vessels throughout the path lesion are located within the neuroretina while in the choroid (after separation of the neural retina) only GFAP-positive but no lectin-positive cells can be seen. The involvement of infiltrating inflammatory cells in these remodeling and healing processes remained minimal throughout the study period. During the 4 weeks following krypton laser photocoagulation in the mouse eye, processes of wound healing and remodeling appear to be driven by cells (and vessels) originating from the retina.

  4. Remodeling the Vascular Microenvironment of Glioblastoma with α-Particles.

    Science.gov (United States)

    Behling, Katja; Maguire, William F; Di Gialleonardo, Valentina; Heeb, Lukas E M; Hassan, Iman F; Veach, Darren R; Keshari, Kayvan R; Gutin, Philip H; Scheinberg, David A; McDevitt, Michael R

    2016-11-01

    Tumors escape antiangiogenic therapy by activation of proangiogenic signaling pathways. Bevacizumab is approved for the treatment of recurrent glioblastoma, but patients inevitably develop resistance to this angiogenic inhibitor. We previously investigated targeted α-particle therapy with 225 Ac-E4G10 as an antivascular approach and showed increased survival and tumor control in a high-grade transgenic orthotopic glioblastoma model. Here, we investigated changes in tumor vascular morphology and functionality caused by 225 Ac-E4G10. We investigated remodeling of the tumor microenvironment in transgenic Ntva glioblastoma mice using a therapeutic 7.4-kBq dose of 225 Ac-E4G10. Immunofluorescence and immunohistochemical analyses imaged morphologic changes in the tumor blood-brain barrier microenvironment. Multicolor flow cytometry quantified the endothelial progenitor cell population in the bone marrow. Diffusion-weighted MR imaged functional changes in the tumor vascular network. The mechanism of drug action is a combination of remodeling of the glioblastoma vascular microenvironment, relief of edema, and depletion of regulatory T and endothelial progenitor cells. The primary remodeling event is the reduction of both endothelial and perivascular cell populations. Tumor-associated edema and necrosis were lessened, resulting in increased perfusion and reduced diffusion. Pharmacologic uptake of dasatinib into tumor was enhanced after α-particle therapy. Targeted antivascular α-particle radiation remodels the glioblastoma vascular microenvironment via a multimodal mechanism of action and provides insight into the vascular architecture of platelet-derived growth factor-driven glioblastoma. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  5. Effect of heat transfer on unsteady MHD flow of blood in a permeable vessel in the presence of non-uniform heat source

    Directory of Open Access Journals (Sweden)

    A. Sinha

    2016-09-01

    Full Text Available This paper presents a theoretical analysis of blood flow and heat transfer in a permeable vessel in the presence of an external magnetic field. The unsteadiness in the coupled flow and temperature fields is considered to be caused due to the time-dependent stretching velocity and the surface temperature of the vessel. The non-uniform heat source/sink effect on blood flow and heat transfer is taken into account. This study is of potential value in the clinical treatment of cardiovascular disorders accompanied by accelerated circulation. The problem is treated mathematically by reducing it to a system of coupled nonlinear differential equations, which have been solved by using similarity transformation and boundary layer approximation. The resulting nonlinear coupled ordinary differential equations are solved numerically by using an implicit finite difference scheme. Computational results are obtained for the velocity, temperature, the skin-friction coefficient and the rate of heat transfer in the vessel. The estimated results are compared with another analytical study reported earlier in scientific literatures. The present study reveals that the heat transfer rate is enhanced as the value of the unsteadiness parameter increases, but it reduces as the space-dependence parameter for heat source/sink increases.

  6. Amlodipine and Atorvastatin Improved Hypertensive Cardiac Remodeling through Regulation of MMPs/TIMPs in SHR Rats

    Directory of Open Access Journals (Sweden)

    Jingchao Lu

    2016-06-01

    Full Text Available Background: MMPs/TIMPs system is well known to play important roles in pressure overload-induced cardiac remodeling, and Amlodipine and Atorvastatin have been showed to exert favourable protective effects on cardiovascular disease, however, it is not clear whether Amlodipine and Atorvastatin can improve hypertensive cardiac remodeling and whether the MMPs/TIMPs system is involved. The present study aims to answer these questions. Methods: 36 weeks old male spontaneous hypertension (SHR rats were randomly divided into four groups: 1. SHR control group, 2. Amlodipine alone (10 mg/kg/d group, 3. Atorvastatin alone (10 mg/kg/d group, 4.Combination of Amlodipine and Atorvastatin (10 mg/kg/d for each group. Same gender, weight and age of Wistar-Kyoto (WKY rats with normal blood pressure were used as normal control. Drugs were administered by oral gavage over 12 weeks. The blood pressure and left ventricle mass index were measured. Enzyme activity of MMP-2 and MMP-9 was assessed with Gelatin zymography. MMP-2, MMP-9, TIMP-1 and TIMP-2 mRNA and protein expression was studied by RT-PCR and Western blot. Single factor ANOVA and LSD-t test were used in statistical analysis. Results: Treatment with Amlodipine alone or combination with atorvastatin significantly decreased blood pressure, left ventricle mass index in SHR rats (P Conclusion: Amlodipine and Atorvastatin could improve ventricular remodeling in SHR rats through intervention with the imbalance of MMP-2/TIMP-2 and MMP-9/TIMP-1 system.

  7. Dissociation between vascular endothelial growth factor receptor-2 and blood vessel density in the caudate nucleus after chronic hydrocephalus.

    Science.gov (United States)

    Deshpande, Abhishek; Dombrowski, Stephen M; Leichliter, Anna; Krajcir, Natalie; Zingales, Nicholas; Inoue, Masahiro; Schenk, Soren; Fukamachi, Kiyotaka; Luciano, Mark G

    2009-11-01

    Chronic hydrocephalus (CH) is characterized by the presence of ventricular enlargement, decreased cerebral blood flow (CBF), and brain tissue oxygen delivery. Although the underlying pathophysiological role of vascular endothelial growth factor (VEGF) is not clear, ischemic-hypoxic events in CH are known to trigger its release. Previously, we have shown increased VEGF receptor-2 (VEGFR-2) and blood vessel density (BVd) in the hippocampus after CH. We investigated changes in neuronal and glial VEGFR-2 density and BVd in the caudate nucleus in an experimental model of CH. Animals with CH were divided into short term (ST, 2 to 4 weeks) and long term (LT, 12 to 16 weeks) and were compared with surgical controls (SCs, 12 to 16 weeks). The cellular and BVds were estimated using immunohistochemical and stereological counting methods. Overall, percentage (%)VEGFR-2 neurons were approximately two times greater in CH (ST, LT) than in SC. By comparison, glial cell %VEGFR-2 was greater by 10% to 17% in ST and 4% to 11% lower in LT compared with that in SC. Blood vessel density was significantly lower in CH than in SC in the superficial caudate. Changes in cerebrospinal fluid ventricular volume and pressure, as well as in CBF did not correlate with either VEGFR-2 or BVd. These observed findings suggest that destructive forces may outweigh angiogenic forces and possibly show a disassociation between VEGFR-2 and BV expressions.

  8. Home Remodeling and Food Allergy Interact Synergistically to Increase the Risk of Atopic Dermatitis

    Directory of Open Access Journals (Sweden)

    Won Seok Lee

    2017-01-01

    Full Text Available Purpose. The purpose of this study was to investigate the effects of home remodeling and food allergy (FA on the development of atopic dermatitis (AD in children. Methods. The Modified International Study of Asthma and Allergies in Childhood questionnaire was used to survey 4,111 children recruited from 3 kindergartens and 6 elementary schools from Seongnam, Korea. Participants’ parents agreed for them to participate in physical examinations, skin prick tests, and blood tests. Results. Home remodeling in the past 12 months (adjusted odds ratio [aOR] 3.40, P=0.006, lifetime diagnosis of FA (aOR 3.95, P<0.001, parental history of AD (aOR 2.67, P=0.001, and FA (aOR 2.35, P=0.004 were independent risk factors for lifetime diagnosis of AD ever. When history of home remodeling and FA were combined, the risk for moderate-to-severe AD by scoring atopic dermatitis (SCORAD score increased (aOR, 7.19, P=0.011, P for interaction = 0.034. Conclusion. Home remodeling, lifetime diagnosis of FA, parental history of AD, and parental history of FA were independent risk factors for AD. In addition, we observed a synergistic interaction between home remodeling and FA in the risk of moderate-to-severe AD.

  9. Wrong theories on the origin of blood vessels: Polybus and De Natura Hominis.

    Science.gov (United States)

    Shoja, Mohammadali M; Tubbs, R Shane; Loukas, Marios; Ardalan, Mohammad R

    2008-06-06

    Polybus of Cos (approximately 400 B.C.) was the son-in-law and the successor of Hippocrates. He is credited with founding the school of Dogmatism, and writing "The Nature of Man" which was important in advancing the theory of the four body humors (humoralism). Some earlier scholars negated Polybus' role as an independent medical figure. However, Corpus Aristotelicum quoted him as having a unique theory regarding the body vasculature which stated that this system was composed of four pairs of blood vessels originating from the head and that these supplied the whole body. In an interpretation of this theory, we opined that numerological mysticism might have been the common motive for both Hippocrates' humoralism and Polybus' theory of the vasculature. A discussion on this issue is presented.

  10. Application of optical coherence tomography for in vivo monitoring of the meningeal lymphatic vessels during opening of blood-brain barrier: mechanisms of brain clearing

    Science.gov (United States)

    Semyachkina-Glushkovskaya, Oxana; Abdurashitov, Arkady; Dubrovsky, Alexander; Bragin, Denis; Bragina, Olga; Shushunova, Nataliya; Maslyakova, Galina; Navolokin, Nikita; Bucharskaya, Alla; Tuchin, Valery; Kurths, Juergen; Shirokov, Alexander

    2017-12-01

    The meningeal lymphatic vessels were discovered 2 years ago as the drainage system involved in the mechanisms underlying the clearance of waste products from the brain. The blood-brain barrier (BBB) is a gatekeeper that strongly controls the movement of different molecules from the blood into the brain. We know the scenarios during the opening of the BBB, but there is extremely limited information on how the brain clears the substances that cross the BBB. Here, using the model of sound-induced opening of the BBB, we clearly show how the brain clears dextran after it crosses the BBB via the meningeal lymphatic vessels. We first demonstrate successful application of optical coherence tomography (OCT) for imaging of the lymphatic vessels in the meninges after opening of the BBB, which might be a new useful strategy for noninvasive analysis of lymphatic drainage in daily clinical practice. Also, we give information about the depth and size of the meningeal lymphatic vessels in mice. These new fundamental data with the applied focus on the OCT shed light on the mechanisms of brain clearance and the role of lymphatic drainage in these processes that could serve as an informative platform for a development of therapy and diagnostics of diseases associated with injuries of the BBB such as stroke, brain trauma, glioma, depression, or Alzheimer disease.

  11. Unsupervised Retinal Vessel Segmentation Using Combined Filters.

    Directory of Open Access Journals (Sweden)

    Wendeson S Oliveira

    Full Text Available Image segmentation of retinal blood vessels is a process that can help to predict and diagnose cardiovascular related diseases, such as hypertension and diabetes, which are known to affect the retinal blood vessels' appearance. This work proposes an unsupervised method for the segmentation of retinal vessels images using a combined matched filter, Frangi's filter and Gabor Wavelet filter to enhance the images. The combination of these three filters in order to improve the segmentation is the main motivation of this work. We investigate two approaches to perform the filter combination: weighted mean and median ranking. Segmentation methods are tested after the vessel enhancement. Enhanced images with median ranking are segmented using a simple threshold criterion. Two segmentation procedures are applied when considering enhanced retinal images using the weighted mean approach. The first method is based on deformable models and the second uses fuzzy C-means for the image segmentation. The procedure is evaluated using two public image databases, Drive and Stare. The experimental results demonstrate that the proposed methods perform well for vessel segmentation in comparison with state-of-the-art methods.

  12. Tumors induce coordinate growth of artery, vein, and lymphatic vessel triads

    International Nuclear Information System (INIS)

    Ruddell, Alanna; Croft, Alexandra; Kelly-Spratt, Karen; Furuya, Momoko; Kemp, Christopher J

    2014-01-01

    Tumors drive blood vessel growth to obtain oxygen and nutrients to support tumor expansion, and they also can induce lymphatic vessel growth to facilitate fluid drainage and metastasis. These processes have generally been studied separately, so that it is not known how peritumoral blood and lymphatic vessels grow relative to each other. The murine B16-F10 melanoma and chemically-induced squamous cell carcinoma models were employed to analyze large red-colored vessels growing between flank tumors and draining lymph nodes. Immunostaining and microscopy in combination with dye injection studies were used to characterize these vessels. Each peritumoral red-colored vessel was found to consist of a triad of collecting lymphatic vessel, vein, and artery, that were all enlarged. Peritumoral veins and arteries were both functional, as detected by intravenous dye injection. The enlarged lymphatic vessels were functional in most mice by subcutaneous dye injection assay, however tumor growth sometimes blocked lymph drainage to regional lymph nodes. Large red-colored vessels also grew between benign papillomas or invasive squamous cell carcinomas and regional lymph nodes in chemical carcinogen-treated mice. Immunostaining of the red-colored vessels again identified the clustered growth of enlarged collecting lymphatics, veins, and arteries in the vicinity of these spontaneously arising tumors. Implanted and spontaneously arising tumors induce coordinate growth of blood and lymphatic vessel triads. Many of these vessel triads are enlarged over several cm distance between the tumor and regional lymph nodes. Lymphatic drainage was sometimes blocked in mice before lymph node metastasis was detected, suggesting that an unknown mechanism alters lymph drainage patterns before tumors reach draining lymph nodes

  13. Tumors induce coordinate growth of artery, vein, and lymphatic vessel triads.

    Science.gov (United States)

    Ruddell, Alanna; Croft, Alexandra; Kelly-Spratt, Karen; Furuya, Momoko; Kemp, Christopher J

    2014-05-21

    Tumors drive blood vessel growth to obtain oxygen and nutrients to support tumor expansion, and they also can induce lymphatic vessel growth to facilitate fluid drainage and metastasis. These processes have generally been studied separately, so that it is not known how peritumoral blood and lymphatic vessels grow relative to each other. The murine B16-F10 melanoma and chemically-induced squamous cell carcinoma models were employed to analyze large red-colored vessels growing between flank tumors and draining lymph nodes. Immunostaining and microscopy in combination with dye injection studies were used to characterize these vessels. Each peritumoral red-colored vessel was found to consist of a triad of collecting lymphatic vessel, vein, and artery, that were all enlarged. Peritumoral veins and arteries were both functional, as detected by intravenous dye injection. The enlarged lymphatic vessels were functional in most mice by subcutaneous dye injection assay, however tumor growth sometimes blocked lymph drainage to regional lymph nodes. Large red-colored vessels also grew between benign papillomas or invasive squamous cell carcinomas and regional lymph nodes in chemical carcinogen-treated mice. Immunostaining of the red-colored vessels again identified the clustered growth of enlarged collecting lymphatics, veins, and arteries in the vicinity of these spontaneously arising tumors. Implanted and spontaneously arising tumors induce coordinate growth of blood and lymphatic vessel triads. Many of these vessel triads are enlarged over several cm distance between the tumor and regional lymph nodes. Lymphatic drainage was sometimes blocked in mice before lymph node metastasis was detected, suggesting that an unknown mechanism alters lymph drainage patterns before tumors reach draining lymph nodes.

  14. Callus remodelling model

    Science.gov (United States)

    Miodowska, Justyna; Bielski, Jan; Kromka-Szydek, Magdalena

    2018-01-01

    The objective of this paper is to investigate the healing process of the callus using bone remodelling approach. A new mathematical model of bone remodelling is proposed including both underload and overload resorption, as well as equilibrium and bone growth states. The created model is used to predict the stress-stimulated change in the callus density. The permanent and intermittent loading programs are considered. The analyses indicate that obtaining a sufficiently high values of the callus density (and hence the elasticity) modulus is only possible using time-varying load parameters. The model predictions also show that intermittent loading program causes delayed callus healing. Understanding how mechanical conditions influence callus remodelling process may be relevant in the bone fracture treatment and initial bone loading during rehabilitation.

  15. Oscillation of Angiogenesis with Vascular Dropout in Diabetic Retinopathy by VESsel GENeration Analysis (VESGEN)

    Science.gov (United States)

    Parsons-Wingerter, Patricia; Radbakrishnan, Krisbnan; Vickerman, Mary B.; Kaiser, Peter K.

    2010-01-01

    PURPOSE. Vascular dropout and angiogenesis are hallmarks of the progression of diabetic retinopathy (DR). However, current evaluation of DR relies on grading of secondary vascular effects, such as microaneurysms and hemorrhages, by clinical examination instead of by evaluation of actual vascular changes. The purpose of this study was to map and quantify vascular changes during progression of DR by VESsel GENeration Analysis (VESGEN). METHODS. In this prospective cross-sectional study, 15 eyes with DR were evaluated with fluorescein angiography (FA) and color fundus photography, and were graded using modified Early Treatment Diabetic Retinopathy Study criteria. FA images were separated by semiautomatic image processing into arterial and venous trees. Vessel length density (L(sub v)), number density (N(sub v)), and diameter (D(sub v)) were analyzed in a masked fashion with VESGEN software. Each vascular tree was automatically segmented into branching generations (G(sub 1)...G(sub 8) or G(sub 9)) by vessel diameter and branching. Vascular remodeling status (VRS) for N(sub v) and L(sub v) was graded 1 to 4 for increasing severity of vascular change. RESULTS. By N(sub v) and L(sub v), VRS correlated significantly with the independent clinical diagnosis of mild to proliferative DR (13/15 eyes). N(sub v) and L(sub v) of smaller vessels (G(sub >=6) increased from VRS1 to VRS2 by 2.4 X and 1.6 X, decreased from VRS2 to VRS3 by 0.4 X and 0.6X, and increased from VRS3 to VRS4 by 1.7 X and 1.5 X (P < 0.01). Throughout DR progression, the density of larger vessels (G(sub 1-5)) remained essentially unchanged, and D(sub v1-5) increased slightly. CONCLUSIONS. Vessel density oscillated with the progression of DR. Alternating phases of angiogenesis/neovascularization and vascular dropout were dominated first by remodeling of arteries and subsequently by veins.

  16. Oscillation of Angiogenesis with Vascular Dropout in Diabetic Retinopathy by VESsel GENeration Analysis (VESGEN)

    Science.gov (United States)

    Parsons-Wingerter, Patricia; Radbakrishnan, Krisbnan; Vickerman, Mary B.; Kaiser, Peter K.

    2010-01-01

    PURPOSE. Vascular dropout and angiogenesis are hallmarks of the progression of diabetic retinopathy (DR). However, current evaluation of DR relies on grading of secondary vascular effects, such as microaneurysms and hemorrhages, by clinical examination instead of by evaluation of actual vascular changes. The purpose of this study was to map and quantify vascular changes during progression of DR by VESsel GENeration Analysis (VESGEN). METHODS. In this prospective cross-sectional study, 15 eyes with DR were evaluated with fluorescein angiography (FA) and color fundus photography, and were graded using modified Early Treatment Diabetic Retinopathy Study criteria. FA images were separated by semiautomatic image processing into arterial and venous trees. Vessel length density (L(sub v)), number density (N(sub v)), and diameter (D(sub v)) were analyzed in a masked fashion with VESGEN software. Each vascular tree was automatically segmented into branching generations (G(sub 1)...G(sub 8) or G(sub 9)) by vessel diameter and branching. Vascular remodeling status (VRS) for N(sub v) and L(sub v) was graded 1 to 4 for increasing severity of vascular change. RESULTS. By N(sub v) and L(sub v), VRS correlated significantly with the independent clinical diagnosis of mild to proliferative DR (13/15 eyes). N(sub v) and L(sub v) of smaller vessels (G(sub >=6) increased from VRS1 to VRS2 by 2.4 X and 1.6 X, decreased from VRS2 to VRS3 by 0.4 X and 0.6X, and increased from VRS3 to VRS4 by 1.7 X and 1.5 X (P dropout were dominated first by remodeling of arteries and subsequently by veins.

  17. Nanobubbles Form at Active Hydrophobic Spots on the Luminal Aspect of Blood Vessels: Consequences for Decompression Illness in Diving and Possible Implications for Autoimmune Disease—An Overview

    Directory of Open Access Journals (Sweden)

    Ran Arieli

    2017-08-01

    Full Text Available Decompression illness (DCI occurs following a reduction in ambient pressure. Decompression bubbles can expand and develop only from pre-existing gas micronuclei. The different hypotheses hitherto proposed regarding the nucleation and stabilization of gas micronuclei have never been validated. It is known that nanobubbles form spontaneously when a smooth hydrophobic surface is submerged in water containing dissolved gas. These nanobubbles may be the long sought-after gas micronuclei underlying decompression bubbles and DCI. We exposed hydrophobic and hydrophilic silicon wafers under water to hyperbaric pressure. After decompression, bubbles appeared on the hydrophobic but not the hydrophilic wafers. In a further series of experiments, we placed large ovine blood vessels in a cooled high pressure chamber at 1,000 kPa for about 20 h. Bubbles evolved at definite spots in all the types of blood vessels. These bubble-producing spots stained positive for lipids, and were henceforth termed “active hydrophobic spots” (AHS. The lung surfactant dipalmitoylphosphatidylcholine (DPPC, was found both in the plasma of the sheep and at the AHS. Bubbles detached from the blood vessel in pulsatile flow after reaching a mean diameter of ~1.0 mm. Bubble expansion was bi-phasic—a slow initiation phase which peaked 45 min after decompression, followed by fast diffusion-controlled growth. Many features of decompression from diving correlate with this finding of AHS on the blood vessels. (1 Variability between bubblers and non-bubblers. (2 An age-related effect and adaptation. (3 The increased risk of DCI on a second dive. (4 Symptoms of neurologic decompression sickness. (5 Preconditioning before a dive. (6 A bi-phasic mechanism of bubble expansion. (7 Increased bubble formation with depth. (8 Endothelial injury. (9 The presence of endothelial microparticles. Finally, constant contact between nanobubbles and plasma may result in distortion of proteins and their

  18. The influence of surrogate blood vessels on the impact response of a physical model of the brain.

    Science.gov (United States)

    Parnaik, Yednesh; Beillas, Philippe; Demetropoulos, Constantine K; Hardy, Warren N; Yang, King H; King, Albert I

    2004-11-01

    Cerebral blood vessels are an integral part of the brain and may play a role in the response of the brain to impact. The purpose of this study was to quantify the effects of surrogate vessels on the deformation patterns of a physical model of the brain under various impact conditions. Silicone gel and tubing were used as surrogates for brain tissue and blood vessels, respectively. Two aluminum cylinders representing a coronal section of the brain were constructed. One cylinder was filled with silicone gel only, and the other was filled with silicone gel and silicone tubing arranged in the radial direction in the peripheral region. An array of markers was embedded in the gel in both cylinders to facilitate strain calculation via high-speed video analysis. Both cylinders were simultaneously subjected to a combination of linear and angular acceleration using a two-segment pendulum. Marker motion was tracked, and maximum shear strain (MSS) and maximum principal strain (MPS) were calculated using markers clustered in groups of three. Four test series were conducted. Peak angular acceleration varied from 2,600 to 26,000 rad/s2, and peak angular speed varied from 17 to 29 rad/s. For a given impact condition, the test-to-test variation of these values was less than 5.5%. For all clusters, the peak MSS and peak MPS for both physical models were less than 26% and 32%, respectively. For 90% of the cluster locations, the absolute value of the difference in peak MSS and peak MPS between the physical models was 4% and 6%, respectively. In the physical model with tubing, strain tended to decrease in the periphery (near to the tubing), while it tended to increase toward the center (away from the tubing). Strain amplitudes were found to be sensitive to the peak angular speeds. In general, this study suggests that the vasculature could influence the deformation response of the brain.

  19. Fractal Branching in Vascular Trees and Networks by VESsel GENeration Analysis (VESGEN)

    Science.gov (United States)

    Parsons-Wingerter, Patricia A.

    2016-01-01

    Vascular patterning offers an informative multi-scale, fractal readout of regulatory signaling by complex molecular pathways. Understanding such molecular crosstalk is important for physiological, pathological and therapeutic research in Space Biology and Astronaut countermeasures. When mapped out and quantified by NASA's innovative VESsel GENeration Analysis (VESGEN) software, remodeling vascular patterns become useful biomarkers that advance out understanding of the response of biology and human health to challenges such as microgravity and radiation in space environments.

  20. Blood Clotting and Pregnancy

    Medline Plus

    Full Text Available ... Blood Clots Blood Clotting and Pregnancy Clots and Travel DVT Myths vs. Facts Blood Disorder Fact Sheets ... that occurs when a DVT breaks off and travels to the blood vessels of the lungs. DVT ...

  1. Tribbles 3: A potential player in diabetic aortic remodelling.

    Science.gov (United States)

    Ti, Yun; Xie, Guo-lu; Wang, Zhi-hao; Ding, Wen-yuan; Zhang, Yun; Zhong, Ming; Zhang, Wei

    2016-01-01

    Tribbles 3, whose expression is up-regulated by insulin resistance, was confirmed to be involved in diabetic cardiomyopathy in our previous study. However, it is not known whether Tribbles 3 has a role on conduit arteries such as the aorta in diabetes. Type 2 diabetic rat model was induced by high-fat diet and low-dose streptozotocin. We evaluated the characteristics of diabetic rats by serial ultrasonography and histopathologic analyses of aortic wall architecture. Diabetic rats displayed increased aortic medial thickness, excessive collagen deposition, diminished elastic fibres and reduced vascular compliance together with Tribbles 3 overexpression. To further investigate the role of Tribbles 3 in aortic remodelling, we used Tribbles 3 gene silencing in vivo 12 weeks after onset of diabetes. Silence of Tribbles 3 significantly reversed pathological aortic remodelling without blood pressure modification. In Tribbles 3-small interfering RNA group, medial thickness and perivascular fibrosis were markedly decreased; moreover, there were prominent reductions in collagen content and collagen/elastin ratio, resulting in an improved arterial compliance. Additionally, with Tribbles 3 silencing, the diminished phosphorylation of PI3K/Akt was restored, and increased activation of MKK4/JNK was decreased. Silence of Tribbles 3 is potent in mediating reversal of aortic remodelling, implicating that Tribbles 3 is proposed to be a potential therapeutic target for vascular complication in diabetes. © The Author(s) 2015.

  2. A confocal scanning laser ophthalmoscope for retinal vessel oximetry

    Science.gov (United States)

    Lompado, Arthur

    Measurement of a person's blood oxygen saturation has long been recognized as a useful metric for the characterizing ailments ranging from chronic respiratory disorders to acute, potentially life threatening, traumas. The ubiquity of oxygen saturation monitors in the medical field, including portable pulse oximeters and laboratory based CO-oximeters, is a testament to the importance of this technique. The work presented here documents the design, fabrication and development of a unique type of oxygen saturation monitor, a confocal scanning retinal vessel oximeter, with the potential to expand the usefulness of the present devices. A large part of the knowledge base required to construct the instrument comes from the consideration of light scattering by red blood cells in a blood vessel. Therefore, a substantial portion of this work is devoted to the process of light scattering by whole human blood and its effects on the development of a more accurate oximeter. This light scattering effect has been both measured and modeled stochastically to determine its contribution to the measured oximeter signal. It is shown that, although well accepted in the published literature, the model only correlates marginally to the measurements due to inherent limitations imposed by the model assumptions. Nonetheless, enough material has been learned about the scattering to allow development of a mathematical model for the interaction of light with blood in a vessel, and this knowledge has been applied to the data reduction of the present oximeter. This data reduction technique has been tested in a controlled experiment employing a model eye with a blood filled mock retinal vessel. It will be shown that the presently developed technique exhibited strong correlation between the known blood oxygen saturation and that calculated by the new system.

  3. Analytical prediction of the heat transfer from a blood vessel near the skin surface when cooled by a symmetrical cooling strip

    Science.gov (United States)

    Chato, J. C.; Shitzer, A.

    1971-01-01

    An analytical method was developed to estimate the amount of heat extracted from an artery running close to the skin surface which is cooled in a symmetrical fashion by a cooling strip. The results indicate that the optimum width of a cooling strip is approximately three times the depth to the centerline of the artery. The heat extracted from an artery with such a strip is about 0.9 w/m-C which is too small to affect significantly the temperature of the blood flow through a main blood vessel, such as the carotid artery. The method is applicable to veins as well.

  4. Agmatine Modulation of Noradrenergic Neurotransmission in Isolated Rat Blood Vessels.

    Science.gov (United States)

    Török, Jozef; Zemančíková, Anna

    2016-06-30

    Agmatine, a vasoactive metabolite of L-arginine, is widely distributed in mammalian tissues including blood vessels. Agmatine binding to imidazoline and α₂-adrenoceptors induces a variety of physiological and pharmacological effects. We investigated the effect of agmatine on contractile responses of the rat pulmonary artery and portal vein induced by electrical stimulation of perivascular nerves and by exogenous adrenergic substances. Experiments were performed on isolated segments of rat main pulmonary artery and its extralobular branches, and portal vein suspended in organ bath containing modified Krebs bicarbonate solution and connected to a force-displacement transducer for isometric tension recording. Electrical field stimulation (EFS) produced tetrodotoxin-sensitive contractile responses of pulmonary artery and portal vein. Besides the well known vasorelaxant actions, we found that agmatine also produced a concentration-dependent inhibition of neurogenic contractions induced by EFS in pulmonary arteries; however, the agmatine treatment did not influence the responses to exogenous noradrenaline. The inhibitory effect on EFS-induced contractions was not abolished by the α₂-adrenoceptor antagonist rauwolscine. In portal vein, in contrast, agmatine increased spontaneous mechanical contractions and enhanced the contractions induced by EFS. The results suggest that agmatine can significantly influence vascular function of pulmonary arteries and portal veins by modulating sympathetically mediated vascular contractions by pre- and postsynaptic mechanisms.

  5. Retinal blood vessel segmentation in high resolution fundus photographs using automated feature parameter estimation

    Science.gov (United States)

    Orlando, José Ignacio; Fracchia, Marcos; del Río, Valeria; del Fresno, Mariana

    2017-11-01

    Several ophthalmological and systemic diseases are manifested through pathological changes in the properties and the distribution of the retinal blood vessels. The characterization of such alterations requires the segmentation of the vasculature, which is a tedious and time-consuming task that is infeasible to be performed manually. Numerous attempts have been made to propose automated methods for segmenting the retinal vasculature from fundus photographs, although their application in real clinical scenarios is usually limited by their ability to deal with images taken at different resolutions. This is likely due to the large number of parameters that have to be properly calibrated according to each image scale. In this paper we propose to apply a novel strategy for automated feature parameter estimation, combined with a vessel segmentation method based on fully connected conditional random fields. The estimation model is learned by linear regression from structural properties of the images and known optimal configurations, that were previously obtained for low resolution data sets. Our experiments in high resolution images show that this approach is able to estimate appropriate configurations that are suitable for performing the segmentation task without requiring to re-engineer parameters. Furthermore, our combined approach reported state of the art performance on the benchmark data set HRF, as measured in terms of the F1-score and the Matthews correlation coefficient.

  6. Renal blood flow and oxygenation drive nephron progenitor differentiation.

    Science.gov (United States)

    Rymer, Christopher; Paredes, Jose; Halt, Kimmo; Schaefer, Caitlin; Wiersch, John; Zhang, Guangfeng; Potoka, Douglas; Vainio, Seppo; Gittes, George K; Bates, Carlton M; Sims-Lucas, Sunder

    2014-08-01

    During kidney development, the vasculature develops via both angiogenesis (branching from major vessels) and vasculogenesis (de novo vessel formation). The formation and perfusion of renal blood vessels are vastly understudied. In the present study, we investigated the regulatory role of renal blood flow and O2 concentration on nephron progenitor differentiation during ontogeny. To elucidate the presence of blood flow, ultrasound-guided intracardiac microinjection was performed, and FITC-tagged tomato lectin was perfused through the embryo. Kidneys were costained for the vasculature, ureteric epithelium, nephron progenitors, and nephron structures. We also analyzed nephron differentiation in normoxia compared with hypoxia. At embryonic day 13.5 (E13.5), the major vascular branches were perfused; however, smaller-caliber peripheral vessels remained unperfused. By E15.5, peripheral vessels started to be perfused as well as glomeruli. While the interior kidney vessels were perfused, the peripheral vessels (nephrogenic zone) remained unperfused. Directly adjacent and internal to the nephrogenic zone, we found differentiated nephron structures surrounded and infiltrated by perfused vessels. Furthermore, we determined that at low O2 concentration, little nephron progenitor differentiation was observed; at higher O2 concentrations, more differentiation of the nephron progenitors was induced. The formation of the developing renal vessels occurs before the onset of blood flow. Furthermore, renal blood flow and oxygenation are critical for nephron progenitor differentiation. Copyright © 2014 the American Physiological Society.

  7. Endothelial remodelling and intracellular calcium machinery.

    Science.gov (United States)

    Moccia, F; Tanzi, F; Munaron, L

    2014-05-01

    Rather being an inert barrier between vessel lumen and surrounding tissues, vascular endothelium plays a key role in the maintenance of cardiovascular homeostasis. The de-endothelialization of blood vessels is regarded as the early event that results in the onset of severe vascular disorders, including atherosclerosis, acute myocardial infarction, brain stroke, and aortic aneurysm. Restoration of the endothelial lining may be accomplished by the activation of neighbouring endothelial cells (ECs) freed by contact inhibition and by circulating endothelial progenitor cells (EPCs). Intracellular Ca(2+) signalling is essential to promote wound healing: however, the molecular underpinnings of the Ca(2+) response to injury are yet to be fully elucidated. Similarly, the components of the Ca(2+) toolkit that drive EPC incorporation into denuded vessels are far from being fully elucidated. The present review will survey the current knowledge on the role of Ca(2+) signalling in endothelial repair and in EPC activation. We propose that endothelial regeneration might be boosted by intraluminal release of specific Ca(2+) channel agonists or by gene transfer strategies aiming to enhance the expression of the most suitable Ca(2+) channels at the wound site. In this view, connexin (Cx) channels/hemichannels and store-operated Ca(2+) entry (SOCE) stand amid the most proper routes to therapeutically induce the regrowth of denuded vessels. Cx stimulation might trigger the proliferative and migratory behaviour of ECs facing the lesion site, whereas activation of SOCE is likely to favour EPC homing to the wounded vessel.

  8. Cannulation and continuous cross-sectional area measurement of small blood vessels

    NARCIS (Netherlands)

    VanBavel, E.; Mooij, T.; Giezeman, M. J.; Spaan, J. A.

    1990-01-01

    Techniques have been developed for the study of isolated small arteries. To pressurize and perfuse segments of these vessels, a cannula with a low resistance to flow was developed. This cannula consisted of two concentric micropipettes. The end of a vessel segment was sucked into the inner pipette

  9. Thermographic venous blood flow characterization with external cooling stimulation

    Science.gov (United States)

    Saxena, Ashish; Ng, E. Y. K.; Raman, Vignesh

    2018-05-01

    Experimental characterization of blood flow in a human forearm is done with the application of continuous external cooling based active thermography method. Qualitative and quantitative detection of the blood vessel in a thermal image is done, along with the evaluation of blood vessel diameter, blood flow direction, and velocity in the target blood vessel. Subtraction based image manipulation is performed to enhance the feature contrast of the thermal image acquired after the removal of external cooling. To demonstrate the effect of occlusion diseases (obstruction), an external cuff based occlusion is applied after the removal of cooling and its effect on the skin rewarming is studied. Using external cooling, a transit time method based blood flow velocity estimation is done. From the results obtained, it is evident that an external cooling based active thermography method can be used to develop a diagnosis tool for superficial blood vessel diseases.

  10. Theoretical modelling of physiologically stretched vessel in magnetisable stent assisted magnetic drug targeting application

    International Nuclear Information System (INIS)

    Mardinoglu, Adil; Cregg, P.J.; Murphy, Kieran; Curtin, Maurice; Prina-Mello, Adriele

    2011-01-01

    The magnetisable stent assisted magnetic targeted drug delivery system in a physiologically stretched vessel is considered theoretically. The changes in the mechanical behaviour of the vessel are analysed under the influence of mechanical forces generated by blood pressure. In this 2D mathematical model a ferromagnetic, coiled wire stent is implanted to aid collection of magnetic drug carrier particles in an elastic tube, which has similar mechanical properties to the blood vessel. A cyclic mechanical force is applied to the elastic tube to mimic the mechanical stress and strain of both the stent and vessel while in the body due to pulsatile blood circulation. The magnetic dipole-dipole and hydrodynamic interactions for multiple particles are included and agglomeration of particles is also modelled. The resulting collection efficiency of the mathematical model shows that the system performance can decrease by as much as 10% due to the effects of the pulsatile blood circulation. - Research highlights: →Theoretical modelling of magnetic drug targeting on a physiologically stretched stent-vessel system. →Cyclic mechanical force applied to mimic the mechanical stress and strain of both stent and vessel. →The magnetic dipole-dipole and hydrodynamic interactions for multiple particles is modelled. →Collection efficiency of the mathematical model is calculated for different physiological blood flow and magnetic field strength.

  11. Mural cell associated VEGF is required for organotypic vessel formation.

    Directory of Open Access Journals (Sweden)

    Lasse Evensen

    Full Text Available BACKGROUND: Blood vessels comprise endothelial cells, mural cells (pericytes/vascular smooth muscle cells and basement membrane. During angiogenesis, mural cells are recruited to sprouting endothelial cells and define a stabilizing context, comprising cell-cell contacts, secreted growth factors and extracellular matrix components, that drives vessel maturation and resistance to anti-angiogenic therapeutics. METHODS AND FINDINGS: To better understand the basis for mural cell regulation of angiogenesis, we conducted high content imaging analysis on a microtiter plate format in vitro organotypic blood vessel system comprising primary human endothelial cells co-cultured with primary human mural cells. We show that endothelial cells co-cultured with mural cells undergo an extensive series of phenotypic changes reflective of several facets of blood vessel formation and maturation: Loss of cell proliferation, pathfinding-like cell migration, branching morphogenesis, basement membrane extracellular matrix protein deposition, lumen formation, anastamosis and development of a stabilized capillary-like network. This phenotypic sequence required endothelial-mural cell-cell contact, mural cell-derived VEGF and endothelial VEGFR2 signaling. Inhibiting formation of adherens junctions or basement membrane structures abrogated network formation. Notably, inhibition of mural cell VEGF expression could not be rescued by exogenous VEGF. CONCLUSIONS: These results suggest a unique role for mural cell-associated VEGF in driving vessel formation and maturation.

  12. Characterization of Imidazoline Receptors in Blood Vessels for the Development of Antihypertensive Agents

    Directory of Open Access Journals (Sweden)

    Mei-Fen Chen

    2014-01-01

    Full Text Available It has been indicated that activation of peripheral imidazoline I2-receptor (I-2R may reduce the blood pressure in spontaneously hypertensive rats (SHRs. Also, guanidinium derivatives show the ability to activate imidazoline receptors. Thus, it is of special interest to characterize the I-2R using guanidinium derivatives in blood vessels for development of antihypertensive agent(s. Six guanidinium derivatives including agmatine, amiloride, aminoguanidine, allantoin, canavanine, and metformin were applied in this study. Western blot analysis was used for detecting the expression of imidazoline receptor in tissues of Wistar rats. The isometric tension of aortic rings isolated from male rats was also estimated. The expression of imidazoline receptor on rat aorta was identified. However, guanidinium derivatives for detection of aortic relaxation were not observed except agmatine and amiloride which induced a marked relaxation in isolated aortic rings precontracted with phenylephrine or KCl. Both relaxations induced by agmatine and amiloride were attenuated by glibenclamide at concentration enough to block ATP-sensitive potassium (KATP channels. Meanwhile, only agmatine-induced relaxation was abolished by BU224, a selective antagonist of imidazoline I2-receptors. Taken together, we suggest that agmatine can induce vascular relaxation through activation of peripheral imidazoline I2-receptor to open KATP channels. Thus, agmatine-like compound has the potential to develop as a new therapeutic agent for hypertension in the future.

  13. Patterns of left ventricular remodeling among patients with essential and secondary hypertension

    OpenAIRE

    Radulescu,Dan; Stoicescu,Laurentiu; Buzdugan,Elena; Donca,Valer

    2013-01-01

    Background: High blood pressure causes left ventricular hypertrophy, which is a negative prognostic factor among hypertensive patients. Aim: To assess left ventricular geometric remodeling patterns in patients with essential hypertension or with hypertension secondary to parenchymal renal disease. Material and Methods: We analyzed data from echocardiograms performed in 250patients with essential hypertension (150 females) and 100 patients with secondary hypertension (60 females). The interven...

  14. Blood circulation in the ascidian tunicate Corella inflata (Corellidae)

    Science.gov (United States)

    2016-01-01

    The body of the ascidian tunicate Corella inflata is relatively transparent. Thus, the circulatory system can be visualized by injecting high molecular weight fluorescein labeled dextran into the heart or the large vessels at the ends of the heart without surgery to remove the body wall. In addition, after staining with neutral red, the movement of blood cells can be easily followed to further characterize the circulatory system. The heart is two gently curved concentric tubes extending across the width of the animal. The inner myocardial tube has a partial constriction approximately in the middle. As in other tunicates, the heart is peristaltic and periodically reverses direction. During the branchial phase blood leaves the anterior end of the heart by two asymmetric vessels that connect to the two sides of the branchial basket. Blood then flows in both transverse directions through a complex system of ducts in the basket into large ventral and dorsal vessels which carry blood back to the visceral organs in the posterior of the animal. During the visceral phase blood leaves the posterior end of the heart in two vessels that repeatedly bifurcate and fan into the stomach and gonads. Blood velocity, determined by following individual cells in video frames, is high and pulsatory near the heart. A double peak in velocity at the maximum may be due to the constriction in the middle of the heart tube. Blood velocity progressively decreases with distance from the heart. In peripheral regions with vessels of small diameter blood cells frequently collide with vessel walls and cell motion is erratic. The estimated volume of blood flow during each directional phase is greater than the total volume of the animal. Circulating blood cells are confined to vessels or ducts in the visible parts of the animal and retention of high molecular weight dextran in the vessels is comparable to that seen in vertebrates. These are characteristics of a closed circulatory system. PMID:27994977

  15. The Physics of Coronary Blood Flow

    CERN Document Server

    Zamir, M

    2005-01-01

    Coronary blood flow is blood flow to the heart for its own metabolic needs. In the most common form of heart disease there is a disruption in this flow because of obstructive disease in the vessels that carry the flow. The subject of coronary blood flow is therefore associated mostly with the pathophysiology of this disease, rarely with dynamics or physics. Yet, the system responsible for coronary blood flow, namely the "coronary circulation," is a highly sophisticated dynamical system in which the dynamics and physics of the flow are as important as the integrity of the conducting vessels. While an obstruction in the conducting vessels is a fairly obvious and clearly visible cause of disruption in coronary blood flow, any discord in the complex dynamics of the system can cause an equally grave, though less conspicuous, disruption in the flow. This book is devoted specifically to the dynamics and physics of coronary blood flow. While relevance to the clinical and pathophysiological issues is clearly maintaine...

  16. Mutation of p107 exacerbates the consequences of Rb loss in embryonic tissues and causes cardiac and blood vessel defects.

    Science.gov (United States)

    Berman, Seth D; West, Julie C; Danielian, Paul S; Caron, Alicia M; Stone, James R; Lees, Jacqueline A

    2009-09-01

    The retinoblastoma tumor-suppressor protein, pRb, is a member of the pocket protein family that includes p107 and p130. These proteins have well-defined roles in regulating entry into and exit from the cell cycle and also have cell cycle-independent roles in facilitating differentiation. Here we investigate the overlap between pocket protein's function during embryonic development by using conditional mutant alleles to generate Rb;p107 double-mutant embryos (DKOs) that develop in the absence of placental defects. These DKOs die between e13.5 and e14.5, much earlier than either the conditional Rb or the germline p107 single mutants, which survive to birth or are largely viable, respectively. Analyses of the e13.5 DKOs shows that p107 mutation exacerbates the phenotypes resulting from pRb loss in the central nervous system and lens, but not in the peripheral nervous system. In addition, these embryos exhibit novel phenotypes, including increased proliferation of blood vessel endothelial cells, and heart defects, including double-outlet right ventricle (DORV). The DORV is caused, at least in part, by a defect in blood vessel endothelial cells and/or heart mesenchymal cells. These findings demonstrate novel, overlapping functions for pRb and p107 in numerous murine tissues.

  17. Orthostatic leg blood volume changes assessed by near-infrared spectroscopy

    DEFF Research Database (Denmark)

    Truijen, J; Kim, Y S; Krediet, C T P

    2012-01-01

    posture, volume accumulation in small blood vessels contributes significantly to the total fluid volume accumulated in the legs. Considering that near-infrared spectroscopy (NIRS) tracks postural blood volume changes within the small blood vessels of the lower leg, we evaluated the NIRS-determined changes......-linear accumulation of blood volume in the small vessels of the leg, with an initial fast phase followed by a more gradual increase at least partly contributing to the relocation of fluid during orthostatic stress....

  18. Knockdown of Zebrafish Blood Vessel Epicardial Substance Results in Incomplete Retinal Lamination

    Directory of Open Access Journals (Sweden)

    Yu-Ching Wu

    2014-01-01

    Full Text Available Cell polarity during eye development determines the normal retinal lamination and differentiation of photoreceptor cells in the retina. In vertebrates, blood vessel epicardial substance (Bves is known to play an important role in the formation and maintenance of the tight junctions essential for epithelial cell polarity. In the current study, we generated a transgenic zebrafish Bves (zbves promoter-EGFP zebrafish line to investigate the expression pattern of Bves in the retina and to study the role of zbves in retinal lamination. Immunostaining with different specific antibodies from retinal cells and transmission electron microscopy were used to identify the morphological defects in normal and Bves knockdown zebrafish. In normal zebrafish, Bves is located at the apical junctions of embryonic retinal neuroepithelia during retinogenesis; later, it is strongly expressed around inner plexiform layer (IPL and retinal pigment epithelium (RPE. In contrast, a loss of normal retinal lamination and cellular polarity was found with undifferentiated photoreceptor cells in Bves knockdown zebrafish. Herein, our results indicated that disruption of Bves will result in a loss of normal retinal lamination.

  19. Involvement of calcitonin gene-related peptide in migraine: regional cerebral blood flow and blood flow velocity in migraine patients

    DEFF Research Database (Denmark)

    Lassen, L.H.; Jacobsen, V.B.; Haderslev, P.A.

    2008-01-01

    Calcitonin gene-related peptide (CGRP)-containing nerves are closely associated with cranial blood vessels. CGRP is the most potent vasodilator known in isolated cerebral blood vessels. CGRP can induce migraine attacks, and two selective CGRP receptor antagonists are effective in the treatment...

  20. Vessel co-option in primary human tumors and metastases: an obstacle to effective anti-angiogenic treatment?

    Science.gov (United States)

    Donnem, Tom; Hu, Jiangting; Ferguson, Mary; Adighibe, Omanma; Snell, Cameron; Harris, Adrian L; Gatter, Kevin C; Pezzella, Francesco

    2013-08-01

    Angiogenesis has been regarded as essential for tumor growth and progression. Studies of many human tumors, however, suggest that their microcirculation may be provided by nonsprouting vessels and that a variety of tumors can grow and metastasize without angiogenesis. Vessel co-option, where tumor cells migrate along the preexisting vessels of the host organ, is regarded as an alternative tumor blood supply. Vessel co-option may occur in many malignancies, but so far mostly reported in highly vascularized tissues such as brain, lung, and liver. In primary and metastatic lung cancer and liver metastasis from different primary origins, as much as 10-30% of the tumors are reported to use this alternative blood supply. In addition, vessel co-option is introduced as a potential explanation of antiangiogenic drug resistance, although the impact of vessel co-option in this clinical setting is still to be further explored. In this review we discuss tumor vessel co-option with specific examples of vessel co-option in primary and secondary tumors and a consideration of the clinical implications of this alternative tumor blood supply.

  1. A new resorbable device for ligation of blood vessels - A pilot study

    Directory of Open Access Journals (Sweden)

    Borg Niklas

    2011-07-01

    Full Text Available Abstract Background During surgery, controlled haemostasis to prevent blood loss is vital for a successful outcome. It can be difficult to ligate vessels located deep in the abdomen. A device that is easy to use and enables secure ligatures could be beneficial. Cable ties made of nylon have been used for ligation but the non-resorbable material caused tissue reactions. The objective of this study was to use a resorbable material to construct a device with a self-locking mechanism and to test its mechanical strength and ligation efficiency. Methods The device was manufactured by injection moulding of polydioxanone, a resorbable polymer used for suture materials. Polydioxanone with inherent viscosities of 1.9 dL/g and 1.3 dL/g were tested. The device consisted of a perforated flexible band which could be pulled through a case with a locking mechanism. After a first version of the device had been tested, some improvements were made. The locking case was downsized, corners were rounded off, the band was made thicker and the mould was redesigned to produce longer devices. Tensile tests were performed with the second version. The first version of the device was used to ligate the ovarian pedicle in a euthanized dog and to test echogenicity of the device with ultrasound. Compression of vessels of the ovarian pedicle was examined by histology. Both versions of the device were tested for haemostasis of and tissue grip on renal arteries in six anaesthetised pigs. Results The tensile strength of the flexible band of the devices with inherent viscosity of 1.9 dL/g was 50.1 ± 5.5 N (range 35.2-62.9 N, n = 11 and the devices with inherent viscosity of 1.3 dL/g had a tensile strength of 39.8 ± 8.1 N (range 18.6-54.2 N, n = 11. Injection moulding of the polymer with lower inherent viscosity resulted in a longer flow distance. Both versions of the device had an effective tissue grip and complete haemostasis of renal arteries was verified. The device attached

  2. Streaming flow from ultrasound contrast agents by acoustic waves in a blood vessel model.

    Science.gov (United States)

    Cho, Eunjin; Chung, Sang Kug; Rhee, Kyehan

    2015-09-01

    To elucidate the effects of streaming flow on ultrasound contrast agent (UCA)-assisted drug delivery, streaming velocity fields from sonicated UCA microbubbles were measured using particle image velocimetry (PIV) in a blood vessel model. At the beginning of ultrasound sonication, the UCA bubbles formed clusters and translated in the direction of the ultrasound field. Bubble cluster formation and translation were faster with 2.25MHz sonication, a frequency close to the resonance frequency of the UCA. Translation of bubble clusters induced streaming jet flow that impinged on the vessel wall, forming symmetric vortices. The maximum streaming velocity was about 60mm/s at 2.25MHz and decreased to 15mm/s at 1.0MHz for the same acoustic pressure amplitude. The effect of the ultrasound frequency on wall shear stress was more noticeable. Maximum wall shear stress decreased from 0.84 to 0.1Pa as the ultrasound frequency decreased from 2.25 to 1.0MHz. The maximum spatial gradient of the wall shear stress also decreased from 1.0 to 0.1Pa/mm. This study showed that streaming flow was induced by bubble cluster formation and translation and was stronger upon sonication by an acoustic wave with a frequency near the UCA resonance frequency. Therefore, the secondary radiant force, which is much stronger at the resonance frequency, should play an important role in UCA-assisted drug delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Cancer cells remodel themselves and vasculature to overcome the endothelial barrier.

    Science.gov (United States)

    Shenoy, Anitha K; Lu, Jianrong

    2016-10-01

    Metastasis refers to the spread of cancer cells from a primary tumor to distant organs mostly via the bloodstream. During the metastatic process, cancer cells invade blood vessels to enter circulation, and later exit the vasculature at a distant site. Endothelial cells that line blood vessels normally serve as a barrier to the movement of cells into or out of the blood. It is thus critical to understand how metastatic cancer cells overcome the endothelial barrier. Epithelial cancer cells acquire increased motility and invasiveness through epithelial-to-mesenchymal transition (EMT), which enables them to move toward vasculature. Cancer cells also express a variety of adhesion molecules that allow them to attach to vascular endothelium. Finally, cancer cells secrete or induce growth factors and cytokines to actively prompt vascular hyperpermeability that compromises endothelial barrier function and facilitates transmigration of cancer cells through the vascular wall. Elucidation of the mechanisms underlying metastatic dissemination may help develop new anti-metastasis therapeutics. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. Re-expression of pro-fibrotic, embryonic preserved mediators in irradiated arterial vessels of the head and neck region.

    Science.gov (United States)

    Möbius, Patrick; Preidl, Raimund H M; Weber, Manuel; Amann, Kerstin; Neukam, Friedrich W; Wehrhan, Falk

    2017-11-01

    Surgical treatment of head and neck malignancies frequently includes microvascular free tissue transfer. Preoperative radiotherapy increases postoperative fibrosis-related complications up to transplant loss. Fibrogenesis is associated with re-expression of embryonic preserved tissue developmental mediators: osteopontin (OPN), regulated by sex-determining region Y‑box 9 (Sox9), and homeobox A9 (HoxA9) play important roles in pathologic tissue remodeling and are upregulated in atherosclerotic vascular lesions; dickkopf-1 (DKK1) inhibits pro-fibrotic and atherogenic Wnt signaling. We evaluated the influence of irradiation on expression of these mediators in arteries of the head and neck region. DKK1, HoxA9, OPN, and Sox9 expression was examined immunohistochemically in 24 irradiated and 24 nonirradiated arteries of the lower head and neck region. The ratio of positive cells to total cell number (labeling index) in the investigated vessel walls was assessed semiquantitatively. DKK1 expression was significantly decreased, whereas HoxA9, OPN, and Sox9 expression were significantly increased in irradiated compared to nonirradiated arterial vessels. Preoperative radiotherapy induces re-expression of embryonic preserved mediators in arterial vessels and may thus contribute to enhanced activation of pro-fibrotic downstream signaling leading to media hypertrophy and intima degeneration comparable to fibrotic development steps in atherosclerosis. These histopathological changes may be promoted by HoxA9-, OPN-, and Sox9-related inflammation and vascular remodeling, supported by downregulation of anti-fibrotic DKK1. Future pharmaceutical strategies targeting these vessel alterations, e. g., bisphosphonates, might reduce postoperative complications in free tissue transfer.

  5. COMPARATIVE ASSESSMENT OF EFFECT OF COMBINED DRUGS OF ACE INHIBITOR AND DIURETIC (“NOLIPREL FORTE” AND “CAPOZIDE” ON CARDIOVASCULAR REMODELING IN HYPERTENSIVE PATIENTS

    Directory of Open Access Journals (Sweden)

    T. D. Kaplanov

    2015-12-01

    Full Text Available Aim. To assess antihypertensive efficacy and effect on cardio-vascular remodeling of combined drugs of ACE inhibitor and diuretic, “Noliprel forte” (NF and “Capozide” (CA, in hypertensive high risk patients.Material and methods. 50 hypertensive (II grade patients (25 men and 25 women, 19-65 years old with high cardio-vascular risk took part in comparative opened randomized study. No one of patients received antihypertensive therapy before study. All patients were randomized for therapy with one of combined drug of ACE inhibitors and diuretic. 25 patients took NF (perindopril 4 mg and indapamide 1,25 mg, and 25 patients -CA (captopril 50 mg and hydrochlorothiazide 25 mg. Duration of observation period was 6 months. Before study, after 3 and 6 months of therapy ambulatory blood pressure monitoring (ABPM, echocardiography, cardiac and vessel Dopplerography, ultrasound scanning of general carotid arteries with detection of intima-media thickness (IMT, pulse wave speed (PWS were held in all patients. Blood bio-chemical analysis was done also.Results. After 3 months 2 patients in NF group and 4 ones in CA group were required to reinforce of ther-apy with additional administration of perindoprile 4 mg and captopril 50 mg respectively. As a result of 6-month of therapy in NF group systolic dlood pressure (BP decreased in 14,0% (р<0,001 and diastolic BP – на 12,9% (р<0,001. CA reduced systolic BP by 17,9% (р<0,0001 and diastolic BP – by 17,5% (р<0,001. 76% and 70% of patients in NF and CA groups, respectively, reached target BP level. Positive dynamic of daily profile of BP was observed according to ABPM data. Cerebral blood flow did not worsen despite of BP decrease. Both drugs decreased in thickness of inter-ventricular septum and left ventricular mass. Besides, NF decreased in thickness of left ventricular posterior wall. Both drugs reduced in IMT and decreased in PWS. NF therapy did not change of blood biochemical parameters. CA

  6. COMPARATIVE ASSESSMENT OF EFFECT OF COMBINED DRUGS OF ACE INHIBITOR AND DIURETIC (“NOLIPREL FORTE” AND “CAPOZIDE” ON CARDIOVASCULAR REMODELING IN HYPERTENSIVE PATIENTS

    Directory of Open Access Journals (Sweden)

    T. D. Kaplanov

    2005-01-01

    Full Text Available Aim. To assess antihypertensive efficacy and effect on cardio-vascular remodeling of combined drugs of ACE inhibitor and diuretic, “Noliprel forte” (NF and “Capozide” (CA, in hypertensive high risk patients.Material and methods. 50 hypertensive (II grade patients (25 men and 25 women, 19-65 years old with high cardio-vascular risk took part in comparative opened randomized study. No one of patients received antihypertensive therapy before study. All patients were randomized for therapy with one of combined drug of ACE inhibitors and diuretic. 25 patients took NF (perindopril 4 mg and indapamide 1,25 mg, and 25 patients -CA (captopril 50 mg and hydrochlorothiazide 25 mg. Duration of observation period was 6 months. Before study, after 3 and 6 months of therapy ambulatory blood pressure monitoring (ABPM, echocardiography, cardiac and vessel Dopplerography, ultrasound scanning of general carotid arteries with detection of intima-media thickness (IMT, pulse wave speed (PWS were held in all patients. Blood bio-chemical analysis was done also.Results. After 3 months 2 patients in NF group and 4 ones in CA group were required to reinforce of ther-apy with additional administration of perindoprile 4 mg and captopril 50 mg respectively. As a result of 6-month of therapy in NF group systolic dlood pressure (BP decreased in 14,0% (р<0,001 and diastolic BP – на 12,9% (р<0,001. CA reduced systolic BP by 17,9% (р<0,0001 and diastolic BP – by 17,5% (р<0,001. 76% and 70% of patients in NF and CA groups, respectively, reached target BP level. Positive dynamic of daily profile of BP was observed according to ABPM data. Cerebral blood flow did not worsen despite of BP decrease. Both drugs decreased in thickness of inter-ventricular septum and left ventricular mass. Besides, NF decreased in thickness of left ventricular posterior wall. Both drugs reduced in IMT and decreased in PWS. NF therapy did not change of blood biochemical parameters. CA

  7. Influence of budesonide and salbutamol atomization inhalation on Th17/ Treg balance in patients with bronchial asthma and its correlation with airway remodeling

    Directory of Open Access Journals (Sweden)

    Kun-Feng Zhang1

    2017-05-01

    Full Text Available Objective: To study the influence of budesonide and salbutamol atomization inhalation on Th17/Treg balance in patients with bronchial asthma and its correlation with airway remodeling. Methods: A total of 90 patients with bronchial asthma who received systemic treatment in our hospital between July 2013 and April 2016 were divided into control group (n=45 and observation group (n=45 according to random number table. Patients in the control group were treated with salbutamol atomization inhalation alone while those in observation group were treated with budesonide and salbutamol atomization inhalation. The Th17/Treg ratio in peripheral blood as well as serum contents of airway remodeling-related indicators was compared between two groups before and after treatment. The correlation between Th17/Treg balance and airway remodeling in patients with bronchial asthma was detected by Pearson test. Results: Before treatment, the differences in peripheral blood Th17/Treg ratio as well as serum contents of inflammatory mediators, growth factor indexes and collagen metabolism indexes were not statistically significant between two groups of patients. After treatment, peripheral blood Th17/Treg ratio in observation group was lower than that in control group, serum CRP, IL-8, IL-13 and TNF-αcontents in observation group were lower than those in control group, serum PDGF-BB, b-FGF and VEGF contents in observation group were lower than those in control group, and serum HA, PCⅢ and LN contents in observation group were lower than those in control group. The Th17/Treg ratio in patients with bronchial asthma after treatment was positively correlated with the levels of airway remodeling-related indexes. Conclusion: Budesonide combined with salbutamol atomization inhalation can optimize the Th17/Treg balance in patients with bronchial asthma, and Th17/Treg is directly correlated to the degree of airway remodeling.

  8. Sensing of Vascular Permeability in Inflamed Vessel of Live Animal

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    Sang A Park

    2018-01-01

    Full Text Available Increase in vascular permeability is a conclusive response in the progress of inflammation. Under controlled conditions, leukocytes are known to migrate across the vascular barriers to the sites of inflammation without severe vascular rupture. However, when inflammatory state becomes excessive, the leakage of blood components may occur and can be lethal. Basically, vascular permeability can be analyzed based on the intensity of blood outflow. To evaluate the amount and rate of leakage in live mice, we performed cremaster muscle exteriorization to visualize blood flow and neutrophil migration. Using two-photon intravital microscopy of the exteriorized cremaster muscle venules, we found that vascular barrier function is transiently and locally disrupted in the early stage of inflammatory condition induced by N-formylmethionyl-leucyl-phenylalanine (fMLP. Measurement of the concentration of intravenously (i.v. injected Texas Red dextran inside and outside the vessels resulted in clear visualization of real-time increases in transient and local vascular permeability increase in real-time manner. We successfully demonstrated repeated leakage from a target site on a blood vessel in association with increasing severity of inflammation. Therefore, compared to other methods, two-photon intravital microscopy more accurately visualizes and quantifies vascular permeability even in a small part of blood vessels in live animals in real time.

  9. [Telescopic adhesive anastomosis of small blood vessel applied in formation of arteriovenous fistula for hemodialysis].

    Science.gov (United States)

    Shen, G; Leng, Y; Rong, G

    1997-03-01

    The formation of an arteriovenous fistual for dialysis by routine interrupted sutures anastomosing the vein and artery is difficult to perform and time-consuming. A new method, telescopic adhesive anastomosis was studied and applied in 10 hemodialysis patients, who were in need of an arteriovenous fistula. The external diameter of the vessels anastomosed was 2.40 +/- 0.20 mm (radial artery) or 2.40 +/- 0.35 mm (cephalic vein). After thorough debridement of the vascular ends, the arterial end was put in the venous lumen. In order to fix the telescopic vessels, two stitches were applied 180 degrees apart from each other and tied. Each stitch was inserted from vein (penetrating the whole wall) to artery (just through the adventitia and partial thickness of the media vasorum). The distance from the stitch to the edge of the vein was 0.5 mm, and that of the artery was approximated to the external diameter of the vessle. The medical adhesive was then applied for sealing the anastomotic adventitia. Ten seconds were given for the solidification of the adhesive. The patients were followed up for 8 months. The patency rate was 100%, and the rate of blood flow was more than 300 ml/min (measured by ultrasonography). It was shown that this method could be managed easily and quickly, and the so-formed fistula would fulfill the need of hemodialysis.

  10. Electrophysiological and structural remodeling in heart failure modulate arrhythmogenesis. 2D simulation study.

    Directory of Open Access Journals (Sweden)

    Juan F Gomez

    Full Text Available Heart failure is operationally defined as the inability of the heart to maintain blood flow to meet the needs of the body and it is the final common pathway of various cardiac pathologies. Electrophysiological remodeling, intercellular uncoupling and a pro-fibrotic response have been identified as major arrhythmogenic factors in heart failure.In this study we investigate vulnerability to reentry under heart failure conditions by incorporating established electrophysiological and anatomical remodeling using computer simulations.The electrical activity of human transmural ventricular tissue (5 cm × 5 cm was simulated using the human ventricular action potential model Grandi et al. under control and heart failure conditions. The MacCannell et al. model was used to model fibroblast electrical activity, and their electrotonic interactions with myocytes. Selected degrees of diffuse fibrosis and variations in intercellular coupling were considered and the vulnerable window (VW for reentry was evaluated following cross-field stimulation.No reentry was observed in normal conditions or in the presence of HF ionic remodeling. However, defined amount of fibrosis and/or cellular uncoupling were sufficient to elicit reentrant activity. Under conditions where reentry was generated, HF electrophysiological remodeling did not alter the width of the VW. However, intermediate fibrosis and cellular uncoupling significantly widened the VW. In addition, biphasic behavior was observed, as very high fibrotic content or very low tissue conductivity hampered the development of reentry. Detailed phase analysis of reentry dynamics revealed an increase of phase singularities with progressive fibrotic components.Structural remodeling is a key factor in the genesis of vulnerability to reentry. A range of intermediate levels of fibrosis and intercellular uncoupling can combine to favor reentrant activity.

  11. Blood flow determinations utilizing digital densitometry

    International Nuclear Information System (INIS)

    Lois, F.; Mankovich, N.J.; Gomes, A.S.

    1987-01-01

    A method of obtaining relative and absolute blood flow measurements from digital densitometry was evaluated with a simulated vessel phantom and a hydrodynamic model. A digital vascular imaging system capable of acquisition in 512 2 and 1024 2 mode was used. Relative and absolute blood flow were measured using parameters derived from the densitometric curve. Since application of densitometric data to absolute flow measurements requires the vessel diameter, an algorithm for vessel size determination was created. Gray scale changes were demonstrated to be linearly related to contrast concentration. The variance of vessel size determination was significantly different in all combinations of 1024 2 and 512 2 imaging with 15 cm or 35 cm field size. The error in vessel size determination was significantly less using the larger 1024 2 matrix and the smaller 15 cm image intensifier field size, as shown by the smaller variance. In relative flow determinations, there was good correlation between the flow and four parameters of the densitometric curve with no significant differences between 512 2 and 1024 2 imaging. Absolute flow determinations had slightly lower correlation to actual flow but were not significantly different from relative flow determinations. Relative and absolute blood flow determinations can be performed adequately with either 512 2 or 1024 2 imaging. The increased accuracy in vessel size determination with 1024 2 imaging makes this high resolution system potentially perferable to determine absolute blood flow. (orig.)

  12. Improvements in the Quantitative Assessment of Cerebral Blood Volume and Flow with the Removal of Vessel Voxels from MR Perfusion Images

    Directory of Open Access Journals (Sweden)

    Michael Mu Huo Teng

    2013-01-01

    Full Text Available Objective. To improve the quantitative assessment of cerebral blood volume (CBV and flow (CBF in the brain voxels from MR perfusion images. Materials and Methods. Normal brain parenchyma was automatically segmented with the time-to-peak criteria after cerebrospinal fluid removal and preliminary vessel voxel removal. Two scaling factors were calculated by comparing the relative CBV and CBF of the segmented normal brain parenchyma with the absolute values in the literature. Using the scaling factors, the relative values were converted to the absolute CBV and CBF. Voxels with either CBV > 8 mL/100 g or CBF > 100 mL/100 g/min were characterized as vessel voxels and were excluded from the quantitative measurements. Results. The segmented brain parenchyma with normal perfusion was consistent with the angiographic findings for each patient. We confirmed the necessity of dual thresholds including CBF and CBV for proper removal of vessel voxels. The scaling factors were 0.208 ± 0.041 for CBV, and 0.168 ± 0.037, 0.172 ± 0.037 for CBF calculated using standard and circulant singular value decomposition techniques, respectively. Conclusion. The automatic scaling and vessel removal techniques provide an alternative method for obtaining improved quantitative assessment of CBV and CBF in patients with thromboembolic cerebral arterial disease.

  13. Inner ocular blood flow responses to an acute decrease in blood pressure in resting humans

    International Nuclear Information System (INIS)

    Ikemura, Tsukasa; Kashima, Hideaki; Yamaguchi, Yuji; Miyaji, Akane; Hayashi, Naoyuki

    2015-01-01

    Whether inner ocular vessels have an autoregulatory response to acute fluctuations in blood pressure is unclear. We tried to examine the validity of acute hypotension elicited by thigh-cuff release as to assess the dynamic autoregulation in the ocular circulation. Blood flow velocity in the superior nasal and inferior temporal retinal arterioles, and in the retinal and choroidal vasculature were measured with the aid of laser speckle flowgraphy before and immediately after an acute decrease in blood pressure in 20 healthy subjects. Acute hypotension was induced by a rapid release of bilateral thigh occlusion cuffs that had been inflated to 220 mmHg for 2 min. The ratio of the relative change in retinal and choroidal blood flow velocity to the relative change in mean arterial blood pressure (MAP) was calculated. Immediately after cuff release, the MAP and blood flows in the all ocular target vessels decreased significantly from the baseline values obtained before thigh-cuff release. The ratio of the relative change in inner ocular blood flow velocity to that in the MAP exceeded 1% / %mmHg. An explicit dynamic autoregulation in inner ocular vessels cannot be demonstrated in response to an acute hypotension induced by the thigh-cuff release technique. (paper)

  14. Erythropoietin-enhanced endothelial progenitor cell recruitment in peripheral blood and renal vessels during experimental acute kidney injury in rats.

    Science.gov (United States)

    Cakiroglu, Figen; Enders-Comberg, Sora Maria; Pagel, Horst; Rohwedel, Jürgen; Lehnert, Hendrik; Kramer, Jan

    2016-03-01

    Beneficial effects of erythropoietin (EPO) have been reported in acute kidney injury (AKI) when administered prior to induction of AKI. We studied the effects of EPO administration on renal function shortly after ischemic AKI. For this purpose, rats were subjected to renal ischemia for 30 min and EPO was administered at a concentration of 500 U/kg either i.v. as a single shot directly after ischemia or with an additional i.p. dose until 3 days after surgery. The results were compared with AKI rats without EPO application and a sham-operated group. Renal function was assessed by measurement of serum biochemical markers, histological grading, and using an isolated perfused kidney (IPK) model. Furthermore, we performed flow cytometry to analyze the concentration of endothelial progenitor cells (EPCs) in the peripheral blood and renal vessels. Following EPO application, there was only a statistically non-significant tendency of serum creatinine and urea to improve, particularly after daily EPO application. Renal vascular resistance and the renal perfusion rate were not significantly altered. In the histological analysis, acute tubular necrosis was only marginally ameliorated following EPO administration. In summary, we could not demonstrate a significant improvement in renal function when EPO was applied after AKI. Interestingly, however, EPO treatment resulted in a highly significant increase in CD133- and CD34-positive EPC both in the peripheral blood and renal vessels. © 2015 International Federation for Cell Biology.

  15. What is cerebral small vessel disease?

    International Nuclear Information System (INIS)

    Onodera, Osamu

    2011-01-01

    An accumulating amount of evidence suggests that the white matter hyperintensities on T 2 weighted brain magnetic resonance imaging predict an increased risk of dementia and gait disturbance. This state has been proposed as cerebral small vessel disease, including leukoaraiosis, Binswanger's disease, lacunar stroke and cerebral microbleeds. However, the concept of cerebral small vessel disease is still obscure. To understand the cerebral small vessel disease, the precise structure and function of cerebral small vessels must be clarified. Cerebral small vessels include several different arteries which have different anatomical structures and functions. Important functions of the cerebral small vessels are blood-brain barrier and perivasucular drainage of interstitial fluid from the brain parenchyma. Cerebral capillaries and glial endfeet, take an important role for these functions. However, the previous pathological investigations on cerebral small vessels have focused on larger arteries than capillaries. Therefore little is known about the pathology of capillaries in small vessel disease. The recent discoveries of genes which cause the cerebral small vessel disease indicate that the cerebral small vessel diseases are caused by a distinct molecular mechanism. One of the pathological findings in hereditary cerebral small vessel disease is the loss of smooth muscle cells, which is an also well-recognized finding in sporadic cerebral small vessel disease. Since pericytes have similar character with the smooth muscle cells, the pericytes should be investigated in these disorders. In addition, the loss of smooth muscle cells may result in dysfunction of drainage of interstitial fluid from capillaries. The precise correlation between the loss of smooth muscle cells and white matter disease is still unknown. However, the function that is specific to cerebral small vessel may be associated with the pathogenesis of cerebral small vessel disease. (author)

  16. Novel Computerized Method for Measurement of Retinal Vessel Diameters

    Directory of Open Access Journals (Sweden)

    Hichem Guedri

    2017-03-01

    Full Text Available Several clinical studies reveal the relationship between alterations in the topologies of the human retinal blood vessel, the outcrop and the disease evolution, such as diabetic retinopathy, hypertensive retinopathy, and macular degeneration. Indeed, the detection of these vascular changes always has gaps. In addition, the manual steps are slow, which may be subjected to a bias of the perceiver. However, we can overcome these troubles using computer algorithms that are quicker and more accurate. This paper presents and investigates a novel method for measuring the blood vessel diameter in the retinal image. The proposed method is based on a thresholding segmentation and thinning step, followed by the characteristic point determination step by the Douglas-Peucker algorithm. Thereafter, it uses the active contours to detect vessel contour. Finally, Heron’s Formula is applied to assure the calculation of vessel diameter. The obtained results for six sample images showed that the proposed method generated less errors compared to other techniques, which confirms the high performance of the proposed method.

  17. Diabetes Mellitus Associates with Increased Right Ventricular Afterload and Remodeling in Pulmonary Arterial Hypertension.

    Science.gov (United States)

    Whitaker, Morgan E; Nair, Vineet; Sinari, Shripad; Dherange, Parinita A; Natarajan, Balaji; Trutter, Lindsey; Brittain, Evan L; Hemnes, Anna R; Austin, Eric D; Patel, Kumar; Black, Stephen M; Garcia, Joe G N; Yuan Md PhD, Jason X; Vanderpool, Rebecca R; Rischard, Franz; Makino, Ayako; Bedrick, Edward J; Desai, Ankit A

    2018-06-01

    Diabetes mellitus is associated with left ventricular hypertrophy and dysfunction. Parallel studies have also reported associations between diabetes mellitus and right ventricular dysfunction and reduced survival in patients with pulmonary arterial hypertension. However, the impact of diabetes mellitus on the pulmonary vasculature has not been well characterized. We hypothesized that diabetes mellitus and hyperglycemia could specifically influence right ventricular afterload and remodeling in patients with Group I pulmonary arterial hypertension, providing a link to their known susceptibility to right ventricular dysfunction. Using an adjusted model for age, sex, pulmonary vascular resistance, and medication use, associations of fasting blood glucose, glycated hemoglobin, and the presence of diabetes mellitus were evaluated with markers of disease severity in 162 patients with pulmonary arterial hypertension. A surrogate measure of increased pulmonary artery stiffness, elevated pulmonary arterial elastance (P = .012), along with reduced log(pulmonary artery capacitance) (P = .006) were significantly associated with the presence of diabetes mellitus in patients with pulmonary arterial hypertension in a fully adjusted model. Similar associations between pulmonary arterial elastance and capacitance were noted with both fasting blood glucose and glycated hemoglobin. Furthermore, right ventricular wall thickness on echocardiography was greater in pulmonary arterial hypertension patients with diabetes, supporting the link between right ventricular remodeling and diabetes. Cumulatively, these data demonstrate that an increase in right ventricular afterload, beyond pulmonary vascular resistance alone, may influence right ventricular remodeling and provide a mechanistic link between the susceptibility to right ventricular dysfunction in patients with both diabetes mellitus and pulmonary arterial hypertension. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Aerobic Training after Myocardial Infarction: Remodeling Evaluated by Cardiac Magnetic Resonance

    Energy Technology Data Exchange (ETDEWEB)

    Izeli, Nataly Lino; Santos, Aurélia Juliana dos; Crescêncio, Júlio César; Gonçalves, Ana Clara Campagnolo Real; Papa, Valéria; Marques, Fabiana [Divisão de Cardiologia do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto - USP, Ribeirão Preto, SP (Brazil); Pazin-Filho, Antônio [Divisão de Emergência da Faculdade de Medicina de Ribeirão Preto - USP, Ribeirão Preto, SP (Brazil); Gallo-Júnior, Lourenço; Schmidt, André, E-mail: aschmidt@fmrp.usp.br [Divisão de Cardiologia do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto - USP, Ribeirão Preto, SP (Brazil)

    2016-04-15

    Numerous studies show the benefits of exercise training after myocardial infarction (MI). Nevertheless, the effects on function and remodeling are still controversial. To evaluate, in patients after (MI), the effects of aerobic exercise of moderate intensity on ventricular remodeling by cardiac magnetic resonance imaging (CMR). 26 male patients, 52.9 ± 7.9 years, after a first MI, were assigned to groups: trained group (TG), 18; and control group (CG), 8. The TG performed supervised aerobic exercise on treadmill twice a week, and unsupervised sessions on 2 additional days per week, for at least 3 months. Laboratory tests, anthropometric measurements, resting heart rate (HR), exercise test, and CMR were conducted at baseline and follow-up. The TG showed a 10.8% reduction in fasting blood glucose (p = 0.01), and a 7.3-bpm reduction in resting HR in both sitting and supine positions (p < 0.0001). There was an increase in oxygen uptake only in the TG (35.4 ± 8.1 to 49.1 ± 9.6 mL/kg/min, p < 0.0001). There was a statistically significant decrease in the TG left ventricular mass (LVmass) (128.7 ± 38.9 to 117.2 ± 27.2 g, p = 0.0032). There were no statistically significant changes in the values of left ventricular end-diastolic volume (LVEDV) and ejection fraction in the groups. The LVmass/EDV ratio demonstrated a statistically significant positive remodeling in the TG (p = 0.015). Aerobic exercise of moderate intensity improved physical capacity and other cardiovascular variables. A positive remodeling was identified in the TG, where a left ventricular diastolic dimension increase was associated with LVmass reduction.

  19. Aerobic Training after Myocardial Infarction: Remodeling Evaluated by Cardiac Magnetic Resonance

    International Nuclear Information System (INIS)

    Izeli, Nataly Lino; Santos, Aurélia Juliana dos; Crescêncio, Júlio César; Gonçalves, Ana Clara Campagnolo Real; Papa, Valéria; Marques, Fabiana; Pazin-Filho, Antônio; Gallo-Júnior, Lourenço; Schmidt, André

    2016-01-01

    Numerous studies show the benefits of exercise training after myocardial infarction (MI). Nevertheless, the effects on function and remodeling are still controversial. To evaluate, in patients after (MI), the effects of aerobic exercise of moderate intensity on ventricular remodeling by cardiac magnetic resonance imaging (CMR). 26 male patients, 52.9 ± 7.9 years, after a first MI, were assigned to groups: trained group (TG), 18; and control group (CG), 8. The TG performed supervised aerobic exercise on treadmill twice a week, and unsupervised sessions on 2 additional days per week, for at least 3 months. Laboratory tests, anthropometric measurements, resting heart rate (HR), exercise test, and CMR were conducted at baseline and follow-up. The TG showed a 10.8% reduction in fasting blood glucose (p = 0.01), and a 7.3-bpm reduction in resting HR in both sitting and supine positions (p < 0.0001). There was an increase in oxygen uptake only in the TG (35.4 ± 8.1 to 49.1 ± 9.6 mL/kg/min, p < 0.0001). There was a statistically significant decrease in the TG left ventricular mass (LVmass) (128.7 ± 38.9 to 117.2 ± 27.2 g, p = 0.0032). There were no statistically significant changes in the values of left ventricular end-diastolic volume (LVEDV) and ejection fraction in the groups. The LVmass/EDV ratio demonstrated a statistically significant positive remodeling in the TG (p = 0.015). Aerobic exercise of moderate intensity improved physical capacity and other cardiovascular variables. A positive remodeling was identified in the TG, where a left ventricular diastolic dimension increase was associated with LVmass reduction

  20. Monitoring Your Blood Sugar Level

    Science.gov (United States)

    ... and NutritionHealth Insurance: Understanding What It CoversHigh Homocysteine Level: How It Affects Your Blood VesselsUnderstanding Your Medical ... Health Resources Healthcare Management Monitoring Your Blood Sugar Level Monitoring Your Blood Sugar Level Share Print What ...

  1. Molecular magnetic resonance imaging of atherosclerotic vessel wall disease

    Energy Technology Data Exchange (ETDEWEB)

    Noerenberg, Dominik [Charite - University Medicine Berlin, Department of Radiology, Berlin (Germany); University of Munich - Grosshadern, Department of Clinical Radiology, Munich (Germany); Ebersberger, Hans U. [Heart Center Munich-Bogenhausen, Department of Cardiology and Intensive Care Medicine, Munich (Germany); Diederichs, Gerd; Hamm, Bernd [Charite - University Medicine Berlin, Department of Radiology, Berlin (Germany); Botnar, Rene M. [King' s College London, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Makowski, Marcus R. [Charite - University Medicine Berlin, Department of Radiology, Berlin (Germany); King' s College London, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom)

    2016-03-15

    Molecular imaging aims to improve the identification and characterization of pathological processes in vivo by visualizing the underlying biological mechanisms. Molecular imaging techniques are increasingly used to assess vascular inflammation, remodeling, cell migration, angioneogenesis and apoptosis. In cardiovascular diseases, molecular magnetic resonance imaging (MRI) offers new insights into the in vivo biology of pathological vessel wall processes of the coronary and carotid arteries and the aorta. This includes detection of early vascular changes preceding plaque development, visualization of unstable plaques and assessment of response to therapy. The current review focuses on recent developments in the field of molecular MRI to characterise different stages of atherosclerotic vessel wall disease. A variety of molecular MR-probes have been developed to improve the non-invasive detection and characterization of atherosclerotic plaques. Specifically targeted molecular probes allow for the visualization of key biological steps in the cascade leading to the development of arterial vessel wall lesions. Early detection of processes which lead to the development of atherosclerosis and the identification of vulnerable atherosclerotic plaques may enable the early assessment of response to therapy, improve therapy planning, foster the prevention of cardiovascular events and may open the door for the development of patient-specific treatment strategies. (orig.)

  2. Molecular magnetic resonance imaging of atherosclerotic vessel wall disease

    International Nuclear Information System (INIS)

    Noerenberg, Dominik; Ebersberger, Hans U.; Diederichs, Gerd; Hamm, Bernd; Botnar, Rene M.; Makowski, Marcus R.

    2016-01-01

    Molecular imaging aims to improve the identification and characterization of pathological processes in vivo by visualizing the underlying biological mechanisms. Molecular imaging techniques are increasingly used to assess vascular inflammation, remodeling, cell migration, angioneogenesis and apoptosis. In cardiovascular diseases, molecular magnetic resonance imaging (MRI) offers new insights into the in vivo biology of pathological vessel wall processes of the coronary and carotid arteries and the aorta. This includes detection of early vascular changes preceding plaque development, visualization of unstable plaques and assessment of response to therapy. The current review focuses on recent developments in the field of molecular MRI to characterise different stages of atherosclerotic vessel wall disease. A variety of molecular MR-probes have been developed to improve the non-invasive detection and characterization of atherosclerotic plaques. Specifically targeted molecular probes allow for the visualization of key biological steps in the cascade leading to the development of arterial vessel wall lesions. Early detection of processes which lead to the development of atherosclerosis and the identification of vulnerable atherosclerotic plaques may enable the early assessment of response to therapy, improve therapy planning, foster the prevention of cardiovascular events and may open the door for the development of patient-specific treatment strategies. (orig.)

  3. ALK7 Gene Polymorphism is Associated with Metabolic Syndrome Risk and Cardiovascular Remodeling

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Wenchao; Wang, Hui; Zhang, Wei [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Lv, Ruijuan [Department of Emergency, Qilu Hospital of Shandong University, Jinan (China); Wang, Zhihao [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Department of Geriatrics, Qilu Hospital of Shandong University, Jinan (China); Shang, Yuanyuan; Zhang, Yun; Zhong, Ming [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Chen, Yuguo; Tang, Mengxiong, E-mail: tangmengxiongsdu8@163.com [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Department of Emergency, Qilu Hospital of Shandong University, Jinan (China)

    2013-08-15

    Activin receptor-like kinase 7 (ALK7) is a type I receptor for the TGF-β superfamily and has recently been demonstrated to play an important role in the maintenance of metabolic homeostasis. To investigate the association of the ALK7 gene polymorphism with metabolic syndrome (MetS) and cardiovascular remodeling in MetS patients. The single nucleotide polymorphism rs13010956 in the ALK7 gene was genotyped in 351 Chinese subjects undergoing carotid and cardiac ultrasonography. The associations of the ALK7 gene polymorphism with the MetS phenotype, MetS parameters, and cardiovascular ultrasonic features were analyzed. The rs13010956 polymorphism in the ALK7 gene was found to be significantly associated with the MetS phenotype in females (p < 0.05) and was also significantly associated with blood pressure in the total (p < 0.05) and female populations (p < 0.01). Further analysis revealed that rs13010956 was associated with mean intima-media thickness of the carotid arteries in females (p < 0.05). After control for body mass index, blood pressure, fasting blood glucose, and triglycerides, rs13010956 was also found to be significantly associated with left ventricular mass index in the total (p < 0.05) and female populations (p < 0.05). Our findings suggested that the ALK7 gene polymorphism rs13010956 was significantly associated with MetS risk in females and may be involved in cardiovascular remodeling in MetS patients.

  4. ALK7 Gene Polymorphism is Associated with Metabolic Syndrome Risk and Cardiovascular Remodeling

    International Nuclear Information System (INIS)

    Zhang, Wenchao; Wang, Hui; Zhang, Wei; Lv, Ruijuan; Wang, Zhihao; Shang, Yuanyuan; Zhang, Yun; Zhong, Ming; Chen, Yuguo; Tang, Mengxiong

    2013-01-01

    Activin receptor-like kinase 7 (ALK7) is a type I receptor for the TGF-β superfamily and has recently been demonstrated to play an important role in the maintenance of metabolic homeostasis. To investigate the association of the ALK7 gene polymorphism with metabolic syndrome (MetS) and cardiovascular remodeling in MetS patients. The single nucleotide polymorphism rs13010956 in the ALK7 gene was genotyped in 351 Chinese subjects undergoing carotid and cardiac ultrasonography. The associations of the ALK7 gene polymorphism with the MetS phenotype, MetS parameters, and cardiovascular ultrasonic features were analyzed. The rs13010956 polymorphism in the ALK7 gene was found to be significantly associated with the MetS phenotype in females (p < 0.05) and was also significantly associated with blood pressure in the total (p < 0.05) and female populations (p < 0.01). Further analysis revealed that rs13010956 was associated with mean intima-media thickness of the carotid arteries in females (p < 0.05). After control for body mass index, blood pressure, fasting blood glucose, and triglycerides, rs13010956 was also found to be significantly associated with left ventricular mass index in the total (p < 0.05) and female populations (p < 0.05). Our findings suggested that the ALK7 gene polymorphism rs13010956 was significantly associated with MetS risk in females and may be involved in cardiovascular remodeling in MetS patients

  5. Fabrication of subcutaneous veins phantom for vessel visualization system

    Science.gov (United States)

    Cheng, Kai; Narita, Kazuyuki; Morita, Yusuke; Nakamachi, Eiji; Honda, Norihiro; Awazu, Kunio

    2013-09-01

    The technique of subcutaneous veins imaging by using NIR (Near Infrared Radiation) is widely used in medical applications, such as the intravenous injection and the blood sampling. In the previous study, an automatic 3D blood vessel search and automatic blood sampling system was newly developed. In order to validate this NIR imaging system, we adopted the subcutaneous vein in the human arm and its artificial phantom, which imitate the human fat and blood vessel. The human skin and subcutaneous vein is characterized as the uncertainty object, which has the individual specificity, non-accurate depth information, non-steady state and hardly to be fixed in the examination apparatus. On the other hand, the conventional phantom was quite distinct from the human's characteristics, such as the non-multilayer structure, disagreement of optical property. In this study, we develop a multilayer phantom, which is quite similar with human skin, for improvement of NIR detection system evaluation. The phantom consists of three layers, such as the epidermis layer, the dermis layer and the subcutaneous fat layer. In subcutaneous fat layer, we built a blood vessel. We use the intralipid to imitate the optical scattering characteristics of human skin, and the hemoglobin and melanin for the optical absorption characteristics. In this study, we did two subjects. First, we decide the fabrication process of the phantom. Second, we compared newly developed phantoms with human skin by using our NIR detecting system, and confirm the availability of these phantoms.

  6. MDCTA diagnosis of cerebral vessel disease among patients with arterial hypertension

    International Nuclear Information System (INIS)

    Romanko-Hrushchak, Nataliya

    2013-01-01

    to study changes involving cerebral vessels in patients with hypertension and various levels of total cardiovascular risk. One hundred and thirty-four patients underwent CT-angiography of intracranial vessels. Ninety-eight of them were diagnosed with hypertension. Taking into consideration high blood pressure, presence of risk factors and target organ damage subjects were divided into 4 groups: with low, medium, high and very high total cardiovascular risk. Control group included 36 patients. They were not diagnosed with hypertension at the time of examination. One hundred and five patients were examined using a 4-slice CT scanner (Toshiba Asteion 4, Toshiba Medical System, Japan), and 29 patients were examined using a 128-slice scanner (Siemens Definition AS+, Siemens Healthcare, Germany) with an injection system. We used iodine-containing contrast agents such as iodixanol and iopromide for angiography. Anatomical and topographic changes of cerebral vessels were most frequently found in hypertensive patients with high and very high total cardiovascular risk. Narrowing of vertebral vessels was the most common change (27 patients (27.55%), 21 patients (21.43%) had narrowing of the right artery, and 6 (6.12%) subjects – of the left one). Tortuous course of internal carotid arteries at the neck level was visualized in 11 patients (11.22%). Narrowing of A1 segment of anterior cerebral artery was noted in 9 patients (9.18%), of the right one – in 8 patients (8.16%), of the left one – in 1 patient (1.02%). Aneurysmal dilation of intracranial vessels was visualized in 6 patients (6.12%). Saccular aneurysm of left internal carotid artery was diagnosed in 2 patients (2.04%), one patient (1.02%) had right internal carotid artery aneurysm and one patient (1.02%) had an aneurysm of the basilar artery. the most common changes of cerebral vessels diagnosed in MDCTA among patients with hypertension included various degrees of narrowing of vertebral vessels, anterior

  7. Blood flow to long bones indicates activity metabolism in mammals, reptiles and dinosaurs.

    Science.gov (United States)

    Seymour, Roger S; Smith, Sarah L; White, Craig R; Henderson, Donald M; Schwarz-Wings, Daniela

    2012-02-07

    The cross-sectional area of a nutrient foramen of a long bone is related to blood flow requirements of the internal bone cells that are essential for dynamic bone remodelling. Foramen area increases with body size in parallel among living mammals and non-varanid reptiles, but is significantly larger in mammals. An index of blood flow rate through the foramina is about 10 times higher in mammals than in reptiles, and even higher if differences in blood pressure are considered. The scaling of foramen size correlates well with maximum whole-body metabolic rate during exercise in mammals and reptiles, but less well with resting metabolic rate. This relates to the role of blood flow associated with bone remodelling during and following activity. Mammals and varanid lizards have much higher aerobic metabolic rates and exercise-induced bone remodelling than non-varanid reptiles. Foramen areas of 10 species of dinosaur from five taxonomic groups are generally larger than from mammals, indicating a routinely highly active and aerobic lifestyle. The simple measurement holds possibilities offers the possibility of assessing other groups of extinct and living vertebrates in relation to body size, behaviour and habitat.

  8. Self-irradiation of the blood from selected nuclides in nuclear medicine

    International Nuclear Information System (INIS)

    Hänscheid, H; Fernández, M; Eberlein, U; Lassmann, M

    2014-01-01

    Nuclear medicine dosimetry and research in biodosimetry often require the knowledge of the absorbed dose to the blood. This study provides coefficients for the absorbed dose rates to the blood related to the activity concentration in the blood as a function of the vessel radius for radionuclides commonly used in targeted radiotherapy and in PET-diagnostics: C-11, F-18, Ga-68, Y-90, Tc-99 m, I-124, I-131, and Lu-177. The energy deposition patterns after nuclear disintegrations in blood vessel lumina (cylinders homogeneously filled with blood) with radii from 0.01 to 25.0 mm were simulated with the Monte-Carlo radiation transport code MCNPX. An additional contribution from photon radiation from activity in blood in the remainder of the body was taken into account based on a reasonable blood distribution model. The fraction of energy absorbed from non-penetrating radiation in the blood is low in thin blood vessels but approaches the total energy emitted by particles with increasing lumen radius. For photon radiation, irradiation to blood in small vessels is almost completely due to radioactive decays in distant blood distributed throughout the body, whereas the contribution from activity in the vessel becomes dominant for lumen radii exceeding 13 mm. The dependences of the absorbed dose rates on the lumen radius can be described with good accuracy by empirical functions which can be used to determine the absorbed doses to the blood and to the surrounding tissue. (paper)

  9. Nicorandil prevents right ventricular remodeling by inhibiting apoptosis and lowering pressure overload in rats with pulmonary arterial hypertension.

    Directory of Open Access Journals (Sweden)

    Xiang-Rong Zuo

    Full Text Available BACKGROUND: Most of the deaths among patients with severe pulmonary arterial hypertension (PAH are caused by progressive right ventricular (RV pathological remodeling, dysfunction, and failure. Nicorandil can inhibit the development of PAH by reducing pulmonary artery pressure and RV hypertrophy. However, whether nicorandil can inhibit apoptosis in RV cardiomyocytes and prevent RV remodeling has been unclear. METHODOLOGY/PRINCIPAL FINDINGS: RV remodeling was induced in rats by intraperitoneal injection of monocrotaline (MCT. RV systolic pressure (RVSP was measured at the end of each week after MCT injection. Blood samples were drawn for brain natriuretic peptide (BNP ELISA analysis. The hearts were excised for histopathological, ultrastructural, immunohistochemical, and Western blotting analyses. The MCT-injected rats exhibited greater mortality and less weight gain and showed significantly increased RVSP and RV hypertrophy during the second week. These worsened during the third week. MCT injection for three weeks caused pathological RV remodeling, characterized by hypertrophy, fibrosis, dysfunction, and RV mitochondrial impairment, as indicated by increased levels of apoptosis. Nicorandil improved survival, weight gain, and RV function, ameliorated RV pressure overload, and prevented maladaptive RV remodeling in PAH rats. Nicorandil also reduced the number of apoptotic cardiomyocytes, with a concomitant increase in Bcl-2/Bax ratio. 5-hydroxydecanoate (5-HD reversed these beneficial effects of nicorandil in MCT-injected rats. CONCLUSIONS/SIGNIFICANCE: Nicorandil inhibits PAH-induced RV remodeling in rats not only by reducing RV pressure overload but also by inhibiting apoptosis in cardiomyocytes through the activation of mitochondrial ATP-sensitive K(+ (mitoK(ATP channels. The use of a mitoK(ATP channel opener such as nicorandil for PAH-associated RV remodeling and dysfunction may represent a new therapeutic strategy for the amelioration of RV

  10. The Latest Twists in Chromatin Remodeling.

    Science.gov (United States)

    Blossey, Ralf; Schiessel, Helmut

    2018-01-05

    In its most restrictive interpretation, the notion of chromatin remodeling refers to the action of chromatin-remodeling enzymes on nucleosomes with the aim of displacing and removing them from the chromatin fiber (the effective polymer formed by a DNA molecule and proteins). This local modification of the fiber structure can have consequences for the initiation and repression of the transcription process, and when the remodeling process spreads along the fiber, it also results in long-range effects essential for fiber condensation. There are three regulatory levels of relevance that can be distinguished for this process: the intrinsic sequence preference of the histone octamer, which rules the positioning of the nucleosome along the DNA, notably in relation to the genetic information coded in DNA; the recognition or selection of nucleosomal substrates by remodeling complexes; and, finally, the motor action on the nucleosome exerted by the chromatin remodeler. Recent work has been able to provide crucial insights at each of these three levels that add new twists to this exciting and unfinished story, which we highlight in this perspective. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  11. Thermal Expansion of Vitrified Blood Vessels Permeated with DP6 and Synthetic Ice Modulators

    Science.gov (United States)

    Eisenberg, David P.; Taylor, Michael J.; Jimenez-Rios, Jorge L.; Rabin, Yoed

    2014-01-01

    This study provides thermal expansion data for blood vessels permeated with the cryoprotective cocktail DP6, when combined with selected synthetic ice modulators (SIMs): 12% polyethylene glycol 400, 6% 1,3-cyclohexanediol, and 6% 2,3-butanediol. The general classification of SIMs includes molecules that modulate ice nucleation and growth, or possess properties of stabilizing the amorphous state, by virtue of their chemical structure and at concentrations that are not explained on a purely colligative basis. The current study is part of an ongoing effort to characterize thermo-mechanical effects on structural integrity of cryopreserved materials, where thermal expansion is the driving mechanism to thermo-mechanical stress. This study focuses on the lower part of the cryogenic temperature range, where the cryoprotective agent (CPA) behaves as a solid for all practical applications. By combining results obtained in the current study with literature data on the thermal expansion in the upper part of the cryogenic temperature range, unified thermal expansion curves are presented. PMID:24769313

  12. CD4+ LYMPHOCYTES IMPROVE VENOUS BLOOD FLOW IN EXPERIMENTAL ARTERIOVENOUS FISTULAE

    Science.gov (United States)

    Duque, Juan C.; Martinez, Laisel; Mesa, Annia; Wei, Yuntao; Tabbara, Marwan; Salman, Loay H.; Vazquez-Padron, Roberto I.

    2015-01-01

    Background The role of immune cells in arteriovenous fistulae (AVF) maturation is poorly understood and has received, until quite recently, little attention. This study examines the role of T lymphocytes in AVF vascular remodeling. Methods Experimental fistulae were created in athymic rnu nude rats lacking mature T lymphocytes and euthymic control animals by anastomosing the left superior epigastric vein to the nearby femoral artery. Blood flow rates, wall morphology and histological changes were assessed in AVF 21 days after creation. The effect of CD4+ lymphocytes on AVF maturation in athymic animals was analyzed by adoptive transfer of cells after fistula creation. Results The absence of T lymphocytes compromised blood flow in experimental fistulae. Histopathological inspection of AVF from athymic rats revealed that T cell immunodeficiency negatively affected venous vascular remodeling, as evidenced by a reduced lumen, a thick muscular layer and a low number of inflammatory cells compared to control animals. Adoptive transfer of CD4+ lymphocytes from euthymic rats into athymic animals before and after fistula creation improved blood flow and reduced intima-media thickness. Conclusion These results point at the protective role of CD4+ lymphocytes in the remodeling of the AVF vascular wall. PMID:25999254

  13. Calcification remodeling index characterized by cardiac CT as A novel parameter to predict the use of rotational atherectomy for coronary intervention of lesions with moderate to severe calcification

    International Nuclear Information System (INIS)

    Yu, Meng Meng; Li, Yue Hua; Li, Wen Bin; Lu, Zhi Gang; Wei, Meng; Zhang, Jia Yin

    2017-01-01

    To assess the feasibility of calcification characterization by coronary computed tomography angiography (CCTA) to predict the use of rotational atherectomy (RA) for coronary intervention of lesions with moderate to severe calcification. Patients with calcified lesions treated by percutaneous coronary intervention (PCI) who underwent both CCTA and invasive coronary angiography were retrospectively included in this study. Calcification remodeling index was calculated as the ratio of the smallest vessel cross-sectional area of the lesion to the proximal reference luminal area. Other parameters such as calcium volume, regional Agatston score, calcification length, and involved calcium arc quadrant were also recorded. A total of 223 patients with 241 calcified lesions were finally included. Lesions with RA tended to have larger calcium volume, higher regional Agatston score, more involved calcium arc quadrants, and significantly smaller calcification remodeling index than lesions without RA. Receiver operating characteristic curve analysis revealed that the best cutoff value of calcification remodeling index was 0.84 (area under curve = 0.847, p < 0.001). Calcification remodeling index ≤ 0.84 was the strongest independent predictor (odds ratio: 251.47, p < 0.001) for using RA. Calcification remodeling index was significantly correlated with the incidence of using RA to aid PCI. Calcification remodeling index ≤ 0.84 was the strongest independent predictor for using RA prior to stent implantation.

  14. Calcification Remodeling Index Characterized by Cardiac CT as a Novel Parameter to Predict the Use of Rotational Atherectomy for Coronary Intervention of Lesions with Moderate to Severe Calcification

    Science.gov (United States)

    Yu, Mengmeng; Li, Yuehua; Li, Wenbin; Lu, Zhigang; Wei, Meng

    2017-01-01

    Objective To assess the feasibility of calcification characterization by coronary computed tomography angiography (CCTA) to predict the use of rotational atherectomy (RA) for coronary intervention of lesions with moderate to severe calcification. Materials and Methods Patients with calcified lesions treated by percutaneous coronary intervention (PCI) who underwent both CCTA and invasive coronary angiography were retrospectively included in this study. Calcification remodeling index was calculated as the ratio of the smallest vessel cross-sectional area of the lesion to the proximal reference luminal area. Other parameters such as calcium volume, regional Agatston score, calcification length, and involved calcium arc quadrant were also recorded. Results A total of 223 patients with 241 calcified lesions were finally included. Lesions with RA tended to have larger calcium volume, higher regional Agatston score, more involved calcium arc quadrants, and significantly smaller calcification remodeling index than lesions without RA. Receiver operating characteristic curve analysis revealed that the best cutoff value of calcification remodeling index was 0.84 (area under curve = 0.847, p < 0.001). Calcification remodeling index ≤ 0.84 was the strongest independent predictor (odds ratio: 251.47, p < 0.001) for using RA. Conclusion Calcification remodeling index was significantly correlated with the incidence of using RA to aid PCI. Calcification remodeling index ≤ 0.84 was the strongest independent predictor for using RA prior to stent implantation. PMID:28860893

  15. Calcification remodeling index characterized by cardiac CT as A novel parameter to predict the use of rotational atherectomy for coronary intervention of lesions with moderate to severe calcification

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Meng Meng; Li, Yue Hua; Li, Wen Bin; Lu, Zhi Gang; Wei, Meng; Zhang, Jia Yin [Shanghai Jiao Tong University Affiliated Sixth People' s Hospital, Shanghai (China)

    2017-09-15

    To assess the feasibility of calcification characterization by coronary computed tomography angiography (CCTA) to predict the use of rotational atherectomy (RA) for coronary intervention of lesions with moderate to severe calcification. Patients with calcified lesions treated by percutaneous coronary intervention (PCI) who underwent both CCTA and invasive coronary angiography were retrospectively included in this study. Calcification remodeling index was calculated as the ratio of the smallest vessel cross-sectional area of the lesion to the proximal reference luminal area. Other parameters such as calcium volume, regional Agatston score, calcification length, and involved calcium arc quadrant were also recorded. A total of 223 patients with 241 calcified lesions were finally included. Lesions with RA tended to have larger calcium volume, higher regional Agatston score, more involved calcium arc quadrants, and significantly smaller calcification remodeling index than lesions without RA. Receiver operating characteristic curve analysis revealed that the best cutoff value of calcification remodeling index was 0.84 (area under curve = 0.847, p < 0.001). Calcification remodeling index ≤ 0.84 was the strongest independent predictor (odds ratio: 251.47, p < 0.001) for using RA. Calcification remodeling index was significantly correlated with the incidence of using RA to aid PCI. Calcification remodeling index ≤ 0.84 was the strongest independent predictor for using RA prior to stent implantation.

  16. High expression of insulin receptor on tumour-associated blood vessels in invasive bladder cancer predicts poor overall and progression-free survival.

    Science.gov (United States)

    Roudnicky, Filip; Dieterich, Lothar C; Poyet, Cedric; Buser, Lorenz; Wild, Peter; Tang, Dave; Camenzind, Peter; Ho, Chien Hsien; Otto, Vivianne I; Detmar, Michael

    2017-06-01

    Bladder cancer is a frequently recurring disease with a very poor prognosis once progressed to invasive stages, and tumour-associated blood vessels play a crucial role in this process. In order to identify novel biomarkers associated with progression, we isolated blood vascular endothelial cells (BECs) from human invasive bladder cancers and matched normal bladder tissue, and found that tumour-associated BECs greatly up-regulated the expression of insulin receptor (INSR). High expression of INSR on BECs of invasive bladder cancers was significantly associated with shorter progression-free and overall survival. Furthermore, increased expression of the INSR ligand IGF-2 in invasive bladder cancers was associated with reduced overall survival. INSR may therefore represent a novel biomarker to predict cancer progression. Mechanistically, we observed pronounced hypoxia in human bladder cancer tissue, and found a positive correlation between the expression of the hypoxia marker gene GLUT1 and vascular INSR expression, indicating that hypoxia drives INSR expression in tumour-associated blood vessels. In line with this, exposure of cultured BECs and human bladder cancer cell lines to hypoxia led to increased expression of INSR and IGF-2, respectively, and IGF-2 increased BEC migration through the activation of INSR in vitro. Taken together, we identified vascular INSR expression as a potential biomarker for progression in bladder cancer. Furthermore, our data suggest that IGF-2/INSR mediated paracrine crosstalk between bladder cancer cells and endothelial cells is functionally involved in tumour angiogenesis and may thus represent a new therapeutic target. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  17. A method for increasing the homogeneity of the temperature distribution during magnetic fluid hyperthermia with a Fe-Cr-Nb-B alloy in the presence of blood vessels

    Science.gov (United States)

    Tang, Yundong; Flesch, Rodolfo C. C.; Jin, Tao

    2017-06-01

    Magnetic hyperthermia ablates tumor cells by absorbing the thermal energy from magnetic nanoparticles (MNPs) under an external alternating magnetic field. The blood vessels (BVs) within tumor region can generally reduce treatment effectiveness due to the cooling effect of blood flow. This paper aims to investigate the cooling effect of BVs on the temperature field of malignant tumor regions using a complex geometric model and numerical simulation. For deriving the model, the Navier-Stokes equation for blood flow is combined with Pennes bio-heat transfer equation for human tissue. The effects on treatment temperature caused by two different BV distributions inside a mammary tumor are analyzed through numerical simulation under different conditions of flow rate considering a Fe-Cr-Nb-B alloy, which has low Curie temperature ranging from 42 °C to 45 °C. Numerical results show that the multi-vessel system has more obvious cooling effects than the single vessel one on the temperature field distribution for hyperthermia. Besides, simulation results show that the temperature field within tumor area can also be influenced by the velocity and diameter of BVs. To minimize the cooling effect, this article proposes a treatment method based on the increase of the thermal energy provided to MNPs associated with the adoption of low Curie temperature particles recently reported in literature. Results demonstrate that this approach noticeably improves the uniformity of the temperature field, and shortens the treatment time in a Fe-Cr-Nb-B system, thus reducing the side effects to the patient.

  18. Dual effects of fructose on ChREBP and FoxO1/3α are responsible for AldoB up-regulation and vascular remodelling.

    Science.gov (United States)

    Cao, Wei; Chang, Tuanjie; Li, Xiao-Qiang; Wang, Rui; Wu, Lingyun

    2017-02-01

    Increased production of methylglyoxal (MG) in vascular tissues is one of the causative factors for vascular remodelling in different subtypes of metabolic syndrome, including hypertension and insulin resistance. Fructose-induced up-regulation of aldolase B (AldoB) contributes to increased vascular MG production but the underlying mechanisms are unclear. Serum levels of MG and fructose were determined in diabetic patients with hypertension. MG level had significant positive correlations with blood pressure and fructose level respectively. C57BL/6 mice were fed with control or fructose-enriched diet for 3 months and ultrasonographic and histologic analyses were performed to evaluate arterial structural changes. Fructose-fed mice exhibited hypertension and high levels of serum MG with normal glucose level. Fructose intake increased blood vessel wall thickness and vascular smooth muscle cell (VSMC) proliferation. Western blotting and real-time PCR analysis revealed that AldoB level was significantly increased in both the aorta of fructose-fed mice and the fructose-treated VSMCs, whereas aldolase A (AldoA) expression was not changed. The knockdown of AldoB expression prevented fructose-induced MG overproduction and VSMC proliferation. Moreover, fructose significantly increased carbohydrate-responsive element-binding protein (ChREBP), phosphorylated FoxO1/3α and Akt1 levels. Fructose induced translocation of ChREBP from the cytosol to nucleus and activated AldoB gene expression, which was inhibited by the knockdown of ChREBP. Meanwhile, fructose caused FoxO1/3α shuttling from the nucleus to cytosol and inhibited its binding to AldoB promoter region. Fructose-induced AldoB up-regulation was suppressed by Akt1 inhibitor but enhanced by FoxO1/3α siRNA. Collectively, fructose activates ChREBP and inactivates FoxO1/3α pathways to up-regulate AldoB expression and MG production, leading to vascular remodelling. © 2017 The Author(s). published by Portland Press Limited on

  19. Cellular and Molecular Mechanisms of Bone Remodeling*

    OpenAIRE

    Raggatt, Liza J.; Partridge, Nicola C.

    2010-01-01

    Physiological bone remodeling is a highly coordinated process responsible for bone resorption and formation and is necessary to repair damaged bone and to maintain mineral homeostasis. In addition to the traditional bone cells (osteoclasts, osteoblasts, and osteocytes) that are necessary for bone remodeling, several immune cells have also been implicated in bone disease. This minireview discusses physiological bone remodeling, outlining the traditional bone biology dogma in light of emerging ...

  20. Small vessel vasculitis History, classification, etiology, histopathology, clinic, diagnosis and treatment

    International Nuclear Information System (INIS)

    Iglesias Gamarra, Antonio; Matteson, Eric L; Restrepo, Jose Felix

    2007-01-01

    Small-vessel vasculitis is a convenient descriptor for a wide range of diseases characterized by vascular inflammation of the venules, capillaries, and/or arterioles with pleomorphic clinical manifestations. The classical clinical phenotype is leucocytoclastic vasculitis with palpable purpura, but manifestations vary widely depending upon the organs involved. Histopathologic examination in leucocytoclastic vasculitis reveals angiocentric segmental inflammation, fibrinoid necrosis, and a neutrophilic infiltrate around the blood vessel walls with erythrocyte extravasation. The etiology of small-vessel vasculitis is unknown in many cases, but in others, drugs, post viral syndromes, malignancy, primary vasculitis such as microscopic polyarteritis, and connective tissue disorders are associated, The diagnosis of small- vessel vasculitis relies on a thorough history and physical examination, as well as relevant antibody testing including antinuclear antibody and anti neutrophil cytoplasmic antibody, hepatitis B and C serologies, assessment of complement, immunoglobulins, blood count, serum creatinine liver function tests, urinalysis, radiographic imaging and biopsy. The treatment is based primarily on corticosteroid and immunosuppressive agents

  1. Blood-Vessel Mimicking Structures by Stereolithographic Fabrication of Small Porous Tubes Using Cytocompatible Polyacrylate Elastomers, Biofunctionalization and Endothelialization

    Directory of Open Access Journals (Sweden)

    Birgit Huber

    2016-04-01

    Full Text Available Blood vessel reconstruction is still an elusive goal for the development of in vitro models as well as artificial vascular grafts. In this study, we used a novel photo-curable cytocompatible polyacrylate material (PA for freeform generation of synthetic vessels. We applied stereolithography for the fabrication of arbitrary 3D tubular structures with total dimensions in the centimeter range, 300 µm wall thickness, inner diameters of 1 to 2 mm and defined pores with a constant diameter of approximately 100 µm or 200 µm. We established a rinsing protocol to remove remaining cytotoxic substances from the photo-cured PA and applied thio-modified heparin and RGDC-peptides to functionalize the PA surface for enhanced endothelial cell adhesion. A rotating seeding procedure was introduced to ensure homogenous endothelial monolayer formation at the inner luminal tube wall. We showed that endothelial cells stayed viable and adherent and aligned along the medium flow under fluid-flow conditions comparable to native capillaries. The combined technology approach comprising of freeform additive manufacturing (AM, biomimetic design, cytocompatible materials which are applicable to AM, and biofunctionalization of AM constructs has been introduced as BioRap® technology by the authors.

  2. Combination probe for optically assisted ultrasonic velocity-change imaging aimed at detecting unstable blood vessel plaque

    Science.gov (United States)

    Tanigawa, Shohei; Mano, Kazune; Wada, Kenji; Matsunaka, Toshiyuki; Horinaka, Hiromichi

    2016-04-01

    Blood vessel plaque with a large lipid core is at risk of becoming thrombus and is likely to induce acute heart disease. To prevent this, it is necessary to determine not only the plaque's size but also its chemical composition. We, therefore, made the prototype of a combination probe to diagnose carotid artery plaque. It is used to differentiate propagation characteristics between light spectra and ultrasonic images. By propagating light and ultrasound along a common direction, it is possible to effectively warm the diagnosis domain. Moreover, the probe is thought to be compact and be easy to use for diagnosing human carotid artery plaque. We applied the combination probe to a carotid artery phantom with a lipid area and obtained an image of the ultrasonic velocity change in the fatty area.

  3. Synthesis and characterization of Gadolinium-Lectin conjugates as selective blood-vessel contrast agents for magnetic resonance imaging (MRI)

    International Nuclear Information System (INIS)

    Pashkunova-Martic, I.

    2004-11-01

    Molecular imaging without use of ionizing radiation has recently been developed for both magnetic resonance and ultrasound imaging (MRI, US) and is expected to play a major future role in diagnosis and monitoring of tumours. In MRI, targeted nanoparticle contrast media (CM) with high relaxivities are required in order to obtain adequate signal-to-noise ratios, due to the low number of target sites. The size, charge and chemical constitution of the targeted nanoparticle CM are expected to influence nanoparticle interactions with cells and tissue elements significantly, and hence the targeting, the accumulation and dwell time at the targeted site, and the type and rate of clearance of the nanoparticles. The work reported here aims to characterise and optimise these parameters in mouse and human models, using nanoparticles targeted to a major carbohydrate determinant of the endothelial cell surface which is present in all blood vessels. Specific binding to the endothelium was demonstrated in both living and chemically fixed human vessels and in mice. Long-standing spin-echo and FLASH-3D images were obtained in the vasculature of living mice, in strong contrast to the rapid renal clearance of gadolinium-DTPA chelates which are widely used in the clinic. Nanoparticle size was found to be a major determinant of the biological response, and our data indicate that an optimal nanoparticle size lies between 50-100 nm diameter. We expect that hyperpermeable vessels present in tumours will permit targeting of optimised nanoparticles to the tumour cells, permitting MRI monitoring of the tumour. (author)

  4. Masked hypertension and cardiac remodeling in middle-aged endurance athletes.

    Science.gov (United States)

    Trachsel, Lukas D; Carlen, Frederik; Brugger, Nicolas; Seiler, Christian; Wilhelm, Matthias

    2015-06-01

    Extensive endurance training and arterial hypertension are established risk factors for atrial fibrillation. We aimed to assess the proportion of masked hypertension in endurance athletes and the impact on cardiac remodeling, mechanics, and supraventricular tachycardias (SVT). Male participants of a 10-mile race were recruited and included if office blood pressure was normal (hypertension and normotension group by ambulatory blood pressure. Primary endpoint was diastolic function, expressed as peak early diastolic mitral annulus velocity (E'). Left ventricular global strain, left ventricular mass/volume ratio, left atrial volume index, signal-averaged P-wave duration (SAPWD), and SVT during 24-h Holter monitoring were recorded. From 108 runners recruited, 87 were included in the final analysis. Thirty-three (38%) had masked hypertension. The mean age was 42 ± 8 years. Groups did not differ with respect to age, body composition, cumulative training hours, and 10-mile race time. Athletes with masked hypertension had a lower E' and a higher left ventricular mass/volume ratio. Left ventricular global strain, left atrial volume index, SAPWD, and SVT showed no significant differences between the groups. In multiple linear regression analysis, masked hypertension was independently associated with E' (beta = -0.270, P = 0.004) and left ventricular mass/volume ratio (beta = 0.206, P = 0.049). Cumulative training hours was the only independent predictor for left atrial volume index (beta = 0.474, P hypertension, associated with a lower diastolic function and a higher left ventricular mass/volume ratio, but unrelated to left ventricular systolic function, atrial remodeling, or SVT.

  5. Personal identification based on blood vessels of retinal fundus images

    Science.gov (United States)

    Fukuta, Keisuke; Nakagawa, Toshiaki; Hayashi, Yoshinori; Hatanaka, Yuji; Hara, Takeshi; Fujita, Hiroshi

    2008-03-01

    Biometric technique has been implemented instead of conventional identification methods such as password in computer, automatic teller machine (ATM), and entrance and exit management system. We propose a personal identification (PI) system using color retinal fundus images which are unique to each individual. The proposed procedure for identification is based on comparison of an input fundus image with reference fundus images in the database. In the first step, registration between the input image and the reference image is performed. The step includes translational and rotational movement. The PI is based on the measure of similarity between blood vessel images generated from the input and reference images. The similarity measure is defined as the cross-correlation coefficient calculated from the pixel values. When the similarity is greater than a predetermined threshold, the input image is identified. This means both the input and the reference images are associated to the same person. Four hundred sixty-two fundus images including forty-one same-person's image pairs were used for the estimation of the proposed technique. The false rejection rate and the false acceptance rate were 9.9×10 -5% and 4.3×10 -5%, respectively. The results indicate that the proposed method has a higher performance than other biometrics except for DNA. To be used for practical application in the public, the device which can take retinal fundus images easily is needed. The proposed method is applied to not only the PI but also the system which warns about misfiling of fundus images in medical facilities.

  6. High blood pressure and eye disease

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000999.htm High blood pressure and eye disease To use the sharing features on this page, please enable JavaScript. High blood pressure can damage blood vessels in the retina . The ...

  7. Lattice Boltzmann simulation of behaviour of particles moving in blood vessels under the rolling massage

    International Nuclear Information System (INIS)

    Hou-Hui, Yi; Cai-Feng, Wang; Xiao-Feng, Yang; Hua-Bing, Li

    2009-01-01

    The rolling massage is one of the most important manipulations in Chinese massage, which is expected to eliminate many diseases. Here, the effect of the rolling massage on a pair of particles moving in blood vessels under rolling massage manipulation is studied by the lattice Boltzmann simulation. The simulated results show that the motion of each particle is considerably modified by the rolling massage, and it depends on the relative rolling velocity, the rolling depth, and the distance between particle position and rolling position. Both particles' translational average velocities increase almost linearly as the rolling velocity increases, and obey the same law. The increment of the average relative angular velocity for the leading particle is smaller than that of the trailing one. The result is helpful for understanding the mechanism of the massage and to further develop the rolling techniques. (classical areas of phenomenology)

  8. Expression of PDGF-beta receptor in broilers with pulmonary hypertension induced by cold temperature and its association with pulmonary vascular remodeling.

    Science.gov (United States)

    Li, Jin-Chun; Pan, Jia-Qiang; Huang, Guo-Qing; Tan, Xun; Sun, Wei-Dong; Liu, Yan-Juan; Wang, Xiao-Long

    2010-02-01

    The purpose of the present study was to characterize the relationship between platelet-derived growth factor beta receptor (PDGF-beta receptor) expression and pulmonary vascular remodeling found in broilers subjected to cold temperature beginning at 14 days of age. One hundred and sixty-one-day-old mixed-sex Avian-2000 commercial broilers were randomly divided into a normal temperature group (control) and a cold temperature group (cold). All the birds were brooded in normal temperature up to day 14, with the lighting schedule at 24 h per day. Starting at day 14, birds in the cold group were moved to a pen in the cold house and subjected to low temperature, while birds in the control group were still brooded at normal temperature. On days 14, 23, 30, 37 and 44, the right/total ventricle weight ratio (RV/TV), packed cell volume (PCV), the vessel wall area to vessel total area ratio (WA/TA), mean media thickness in pulmonary arterioles (mMTPA) and the expression of PDGF-beta receptor in pulmonary arterioles were measured, respectively. Cumulative pulmonary hypertension syndrome (PHS) morbidity was recorded in each group. Cool ambient temperature increased PHS morbidity of broilers. The values of WA/TA and mMTPA were also increased significantly compared with control group. PCV values in the cold temperature group were elevated from days 30 to 44, and RV/TV ratios were increased on days 37 and 44. Cold exposure enhanced PDGF-beta receptor expression in pulmonary arterioles, and the PDGF-beta receptor expression was significantly correlated with pulmonary vascular remodeling that was dedicated by increased WA/TA and mMTPA. The results indicated that PDGF-beta and its receptor were involved in the underlying mechanisms of pulmonary vascular remodeling in pulmonary hypertensive broilers. Copyright 2009 Elsevier Ltd. All rights reserved.

  9. Tissue Engineering at the Blood-Contacting Surface: A Review of Challenges and Strategies in Vascular Graft Development.

    Science.gov (United States)

    Radke, Daniel; Jia, Wenkai; Sharma, Dhavan; Fena, Kemin; Wang, Guifang; Goldman, Jeremy; Zhao, Feng

    2018-05-07

    Tissue engineered vascular grafts (TEVGs) are beginning to achieve clinical success and hold promise as a source of grafting material when donor grafts are unsuitable or unavailable. Significant technological advances have generated small-diameter TEVGs that are mechanically stable and promote functional remodeling by regenerating host cells. However, developing a biocompatible blood-contacting surface remains a major challenge. The TEVG luminal surface must avoid negative inflammatory responses and thrombogenesis immediately upon implantation and promote endothelialization. The surface has therefore become a primary focus for research and development efforts. The current state of TEVGs is herein reviewed with an emphasis on the blood-contacting surface. General vascular physiology and developmental challenges and strategies are briefly described, followed by an overview of the materials currently employed in TEVGs. The use of biodegradable materials and stem cells requires careful control of graft composition, degradation behavior, and cell recruitment ability to ensure that a physiologically relevant vessel structure is ultimately achieved. The establishment of a stable monolayer of endothelial cells and the quiescence of smooth muscle cells are critical to the maintenance of patency. Several strategies to modify blood-contacting surfaces to resist thrombosis and control cellular recruitment are reviewed, including coatings of biomimetic peptides and heparin. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Kinetics of cardiac and vascular remodeling by spontaneously hypertensive rats after discontinuation of long-term captopril treatment

    Directory of Open Access Journals (Sweden)

    W.A. Rocha

    2010-04-01

    Full Text Available Angiotensin-converting enzyme inhibitors reduce blood pressure and attenuate cardiac and vascular remodeling in hypertension. However, the kinetics of remodeling after discontinuation of the long-term use of these drugs are unknown. Our objective was to investigate the temporal changes occurring in blood pressure and vascular structure of spontaneously hypertensive rats (SHR. Captopril treatment was started in the pre-hypertensive state. Rats (4 weeks were assigned to three groups: SHR-Cap (N = 51 treated with captopril (1 g/L in drinking water from the 4th to the 14th week; SHR-C (N = 48 untreated SHR; Wistar (N = 47 control rats. Subgroups of animals were studied at 2, 4, and 8 weeks after discontinuation of captopril. Direct blood pressure was recorded in freely moving animals after femoral artery catheterism. The animals were then killed to determine left ventricular hypertrophy (LVH and the aorta fixed at the same pressure measured in vivo. Captopril prevented hypertension (105 ± 3 vs 136 ± 5 mmHg, LVH (2.17 ± 0.05 vs 2.97 ± 0.14 mg/g body weight and the increase in cross-sectional area to luminal area ratio of the aorta (0.21 ± 0.01 vs 0.26 ± 0.02 μm² (SHR-Cap vs SHR-C. However, these parameters increased progressively after discontinuation of captopril (22nd week: 141 ± 2 mmHg, 2.50 ± 0.06 mg/g, 0.27 ± 0.02 μm². Prevention of the development of hypertension in SHR by using captopril during the prehypertensive period prevents the development of cardiac and vascular remodeling. Recovery of these processes follows the kinetic of hypertension development after discontinuation of captopril.

  11. Modification of a Volume-Overload Heart Failure Model to Track Myocardial Remodeling and Device-Related Reverse Remodeling

    Science.gov (United States)

    Tuzun, Egemen; Bick, Roger; Kadipasaoglu, Cihan; Conger, Jeffrey L.; Poindexter, Brian J.; Gregoric, Igor D.; Frazier, O. H.; Towbin, Jeffrey A.; Radovancevic, Branislav

    2011-01-01

    Purpose. To provide an ovine model of ventricular remodeling and reverse remodeling by creating congestive heart failure (CHF) and then treating it by implanting a left ventricular assist device (LVAD). Methods. We induced volume-overload heart failure in 2 sheep; 20 weeks later, we implanted an LVAD and assessed recovery 11 weeks thereafter. We examined changes in histologic and hemodynamic data and levels of cellular markers of CHF. Results. After CHF induction, we found increases in LV end-diastolic pressure, LV systolic and diastolic dimensions, wall thickness, left atrial diameter, and atrial natriuretic protein (ANP) and endothelin-1 (ET-1) levels; β-adrenergic receptor (BAR) and dystrophin expression decreased markedly. Biopsies confirmed LV remodeling. After LVAD support, LV systolic and diastolic dimensions, wall thickness, and mass, and ANP and ET-1 levels decreased. Histopathologic and hemodynamic markers improved, and BAR and dystrophin expression normalized. Conclusions. We describe a successful sheep model for ventricular and reverse remodeling. PMID:22347659

  12. Influencing factors affecting the retinal blood vessel morphology in patients with diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Xiao-Lu Kong

    2017-03-01

    Full Text Available AIM: To analyze the influencing factors affecting retinal blood vessel morphology in patients with diabetes mellitus. METHODS: Totally 312 patients with type 2 diabetes mellitus in our hospital from January 2012 to September 2016 were selected as study subjects. The patients were examined by fundus photography and related laboratory. As grouping factors in the patients'age, sex, disease duration, smoking, drinking, hypertension, hyperlipidemia or diabetic nephropathy, we compared the incidence of retinal vascular changes in different groups. The meaningful factors were introduced into the Logistic regression equation again. Independent risk factors for retinal vascular changes in patients with diabetes mellitus were screened out. RESULTS:In 312 cases of patients with type 2 diabetes mellitus,169 cases were accompanied with retinal vascular abnormalities, and 143 cases were not associated with retinal vascular abnormalities. Univariate analysis showed that age, duration of disease, hypertension, hyperlipidemia or diabetes nephropathy were significantly correlated with retinal vascular morphological changes(PP>0.05. Retinal vascular abnormalities were used as the dependent variable, and the above mentioned factors were grouped as independent variables. By Logistic stepwise regression analysis showed that the course of disease, patients with hypertension or diabetic nephropathy were the independent risk factors of abnormal retinal vascular morphology(PCONCLUSION: The independent risk factors for the occurrence of retinal vascular changes in patients with diabetes mellitus are increased course of disease, hypertension or diabetic nephropathy. Early diagnosis and intervention, to take measures and control blood pressure, reduce kidney damage can reduce the incidence of diabetic retinopathy, and macrovascular disease caused by diabetes, the incidence of adverse cardiovascular and cerebrovascular events.

  13. Multi-level deep supervised networks for retinal vessel segmentation.

    Science.gov (United States)

    Mo, Juan; Zhang, Lei

    2017-12-01

    Changes in the appearance of retinal blood vessels are an important indicator for various ophthalmologic and cardiovascular diseases, including diabetes, hypertension, arteriosclerosis, and choroidal neovascularization. Vessel segmentation from retinal images is very challenging because of low blood vessel contrast, intricate vessel topology, and the presence of pathologies such as microaneurysms and hemorrhages. To overcome these challenges, we propose a neural network-based method for vessel segmentation. A deep supervised fully convolutional network is developed by leveraging multi-level hierarchical features of the deep networks. To improve the discriminative capability of features in lower layers of the deep network and guide the gradient back propagation to overcome gradient vanishing, deep supervision with auxiliary classifiers is incorporated in some intermediate layers of the network. Moreover, the transferred knowledge learned from other domains is used to alleviate the issue of insufficient medical training data. The proposed approach does not rely on hand-crafted features and needs no problem-specific preprocessing or postprocessing, which reduces the impact of subjective factors. We evaluate the proposed method on three publicly available databases, the DRIVE, STARE, and CHASE_DB1 databases. Extensive experiments demonstrate that our approach achieves better or comparable performance to state-of-the-art methods with a much faster processing speed, making it suitable for real-world clinical applications. The results of cross-training experiments demonstrate its robustness with respect to the training set. The proposed approach segments retinal vessels accurately with a much faster processing speed and can be easily applied to other biomedical segmentation tasks.

  14. Dynamics of the ethanolamine glycerophospholipid remodeling network.

    Directory of Open Access Journals (Sweden)

    Lu Zhang

    Full Text Available Acyl chain remodeling in lipids is a critical biochemical process that plays a central role in disease. However, remodeling remains poorly understood, despite massive increases in lipidomic data. In this work, we determine the dynamic network of ethanolamine glycerophospholipid (PE remodeling, using data from pulse-chase experiments and a novel bioinformatic network inference approach. The model uses a set of ordinary differential equations based on the assumptions that (1 sn1 and sn2 acyl positions are independently remodeled; (2 remodeling reaction rates are constant over time; and (3 acyl donor concentrations are constant. We use a novel fast and accurate two-step algorithm to automatically infer model parameters and their values. This is the first such method applicable to dynamic phospholipid lipidomic data. Our inference procedure closely fits experimental measurements and shows strong cross-validation across six independent experiments with distinct deuterium-labeled PE precursors, demonstrating the validity of our assumptions. In contrast, fits of randomized data or fits using random model parameters are worse. A key outcome is that we are able to robustly distinguish deacylation and reacylation kinetics of individual acyl chain types at the sn1 and sn2 positions, explaining the established prevalence of saturated and unsaturated chains in the respective positions. The present study thus demonstrates that dynamic acyl chain remodeling processes can be reliably determined from dynamic lipidomic data.

  15. MR vascular fingerprinting: A new approach to compute cerebral blood volume, mean vessel radius, and oxygenation maps in the human brain.

    Science.gov (United States)

    Christen, T; Pannetier, N A; Ni, W W; Qiu, D; Moseley, M E; Schuff, N; Zaharchuk, G

    2014-04-01

    In the present study, we describe a fingerprinting approach to analyze the time evolution of the MR signal and retrieve quantitative information about the microvascular network. We used a Gradient Echo Sampling of the Free Induction Decay and Spin Echo (GESFIDE) sequence and defined a fingerprint as the ratio of signals acquired pre- and post-injection of an iron-based contrast agent. We then simulated the same experiment with an advanced numerical tool that takes a virtual voxel containing blood vessels as input, then computes microscopic magnetic fields and water diffusion effects, and eventually derives the expected MR signal evolution. The parameter inputs of the simulations (cerebral blood volume [CBV], mean vessel radius [R], and blood oxygen saturation [SO2]) were varied to obtain a dictionary of all possible signal evolutions. The best fit between the observed fingerprint and the dictionary was then determined by using least square minimization. This approach was evaluated in 5 normal subjects and the results were compared to those obtained by using more conventional MR methods, steady-state contrast imaging for CBV and R and a global measure of oxygenation obtained from the superior sagittal sinus for SO2. The fingerprinting method enabled the creation of high-resolution parametric maps of the microvascular network showing expected contrast and fine details. Numerical values in gray matter (CBV=3.1±0.7%, R=12.6±2.4μm, SO2=59.5±4.7%) are consistent with literature reports and correlated with conventional MR approaches. SO2 values in white matter (53.0±4.0%) were slightly lower than expected. Numerous improvements can easily be made and the method should be useful to study brain pathologies. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Expression of the growth factor progranulin in endothelial cells influences growth and development of blood vessels: a novel mouse model.

    Science.gov (United States)

    Toh, Huishi; Cao, Mingju; Daniels, Eugene; Bateman, Andrew

    2013-01-01

    Progranulin is a secreted glycoprotein that regulates cell proliferation, migration and survival. It has roles in development, tumorigenesis, wound healing, neurodegeneration and inflammation. Endothelia in tumors, wounds and placenta express elevated levels of progranulin. In culture, progranulin activates endothelial proliferation and migration. This suggested that progranulin might regulate angiogenesis. It was, however, unclear how elevated endothelial progranulin levels influence vascular growth in vivo. To address this issue, we generated mice with progranulin expression targeted specifically to developing endothelial cells using a Tie2-promoter/enhancer construct. Three Tie2-Grn mouse lines were generated with varying Tie2-Grn copy number, and were called GrnLo, GrnMid, and GrnHi. All three lines showed increased mortality that correlates with Tie2-Grn copy number, with greatest mortality and lowest germline transmission in the GrnHi line. Death of the transgenic animals occurred around birth, and continued for three days after birth. Those that survived beyond day 3 survived into adulthood. Transgenic neonates that died showed vascular abnormalities of varying severity. Some exhibited bleeding into body cavities such as the pericardial space. Smaller localized hemorrhages were seen in many organs. Blood vessels were often dilated and thin-walled. To establish the development of these abnormalities, we examined mice at early (E10.5-14.5) and later (E15.5-17.5) developmental phases. Early events during vasculogenesis appear unaffected by Tie2-Grn as apparently normal primary vasculature had been established at E10.5. The earliest onset of vascular abnormality was at E15.5, with focal cerebral hemorrhage and enlarged vessels in various organs. Aberrant Tie2-Grn positive vessels showed thinning of the basement membrane and reduced investiture with mural cells. We conclude that progranulin promotes exaggerated vessel growth in vivo, with subsequent effects in

  17. Expression of the growth factor progranulin in endothelial cells influences growth and development of blood vessels: a novel mouse model.

    Directory of Open Access Journals (Sweden)

    Huishi Toh

    Full Text Available Progranulin is a secreted glycoprotein that regulates cell proliferation, migration and survival. It has roles in development, tumorigenesis, wound healing, neurodegeneration and inflammation. Endothelia in tumors, wounds and placenta express elevated levels of progranulin. In culture, progranulin activates endothelial proliferation and migration. This suggested that progranulin might regulate angiogenesis. It was, however, unclear how elevated endothelial progranulin levels influence vascular growth in vivo. To address this issue, we generated mice with progranulin expression targeted specifically to developing endothelial cells using a Tie2-promoter/enhancer construct. Three Tie2-Grn mouse lines were generated with varying Tie2-Grn copy number, and were called GrnLo, GrnMid, and GrnHi. All three lines showed increased mortality that correlates with Tie2-Grn copy number, with greatest mortality and lowest germline transmission in the GrnHi line. Death of the transgenic animals occurred around birth, and continued for three days after birth. Those that survived beyond day 3 survived into adulthood. Transgenic neonates that died showed vascular abnormalities of varying severity. Some exhibited bleeding into body cavities such as the pericardial space. Smaller localized hemorrhages were seen in many organs. Blood vessels were often dilated and thin-walled. To establish the development of these abnormalities, we examined mice at early (E10.5-14.5 and later (E15.5-17.5 developmental phases. Early events during vasculogenesis appear unaffected by Tie2-Grn as apparently normal primary vasculature had been established at E10.5. The earliest onset of vascular abnormality was at E15.5, with focal cerebral hemorrhage and enlarged vessels in various organs. Aberrant Tie2-Grn positive vessels showed thinning of the basement membrane and reduced investiture with mural cells. We conclude that progranulin promotes exaggerated vessel growth in vivo, with

  18. Cerebral amyloid angiopathy, blood-brain barrier disruption and amyloid accumulation in SAMP8 mice.

    Science.gov (United States)

    del Valle, Jaume; Duran-Vilaregut, Joaquim; Manich, Gemma; Pallàs, Mercè; Camins, Antoni; Vilaplana, Jordi; Pelegrí, Carme

    2011-01-01

    Cerebrovascular dysfunction and β-amyloid peptide deposition on the walls of cerebral blood vessels might be an early event in the development of Alzheimer's disease. Here we studied the time course of amyloid deposition in blood vessels and blood-brain barrier (BBB) disruption in the CA1 subzone of the hippocampus of SAMP8 mice and the association between these two variables. We also studied the association between the amyloid deposition in blood vessels and the recently described amyloid clusters in the parenchyma, as well as the association of these clusters with vessels in which the BBB is disrupted. SAMP8 mice showed greater amyloid deposition in blood vessels than age-matched ICR-CD1 control mice. Moreover, at 12 months of age the number of vessels with a disrupted BBB had increased in both strains, especially SAMP8 animals. At this age, all the vessels with amyloid deposition showed BBB disruption, but several capillaries with an altered BBB showed no amyloid on their walls. Moreover, amyloid clusters showed no spatial association with vessels with amyloid deposition, nor with vessels in which the BBB had been disrupted. Finally, we can conclude that vascular amyloid deposition seems to induce BBB alterations, but BBB disruption may also be due to other factors. Copyright © 2011 S. Karger AG, Basel.

  19. Placental gene-expression profiles of intrahepatic cholestasis of pregnancy reveal involvement of multiple molecular pathways in blood vessel formation and inflammation.

    Science.gov (United States)

    Du, QiaoLing; Pan, YouDong; Zhang, YouHua; Zhang, HaiLong; Zheng, YaJuan; Lu, Ling; Wang, JunLei; Duan, Tao; Chen, JianFeng

    2014-07-07

    Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-associated liver disease with potentially deleterious consequences for the fetus, particularly when maternal serum bile-acid concentration >40 μM. However, the etiology and pathogenesis of ICP remain elusive. To reveal the underlying molecular mechanisms for the association of maternal serum bile-acid level and fetal outcome in ICP patients, DNA microarray was applied to characterize the whole-genome expression profiles of placentas from healthy women and women diagnosed with ICP. Thirty pregnant women recruited in this study were categorized evenly into three groups: healthy group; mild ICP, with serum bile-acid concentration ranging from 10-40 μM; and severe ICP, with bile-acid concentration >40 μM. Gene Ontology analysis in combination with construction of gene-interaction and gene co-expression networks were applied to identify the core regulatory genes associated with ICP pathogenesis, which were further validated by quantitative real-time PCR and histological staining. The core regulatory genes were mainly involved in immune response, VEGF signaling pathway and G-protein-coupled receptor signaling, implying essential roles of immune response, vasculogenesis and angiogenesis in ICP pathogenesis. This implication was supported by the observed aggregated immune-cell infiltration and deficient blood vessel formation in ICP placentas. Our study provides a system-level insight into the placental gene-expression profiles of women with mild or severe ICP, and reveals multiple molecular pathways in immune response and blood vessel formation that might contribute to ICP pathogenesis.

  20. Long-term streptozotocin-induced diabetes in rats leads to severe damage of brain blood vessels and neurons via enhanced oxidative stress.

    Science.gov (United States)

    Yang, Hongying; Fan, Shourui; Song, Dianping; Wang, Zhuo; Ma, Shungao; Li, Shuqing; Li, Xiaohong; Xu, Mian; Xu, Min; Wang, Xianmo

    2013-02-01

    The aim of this study was to investigate pathophysiological alterations and oxidative stress in various stages of streptozotocin (STZ)‑induced diabetes mellitus (DM) in rats. Male Sprague-Dawley rats (120) were randomized into DM and control groups. Body mass, plasma glucose, glycated hemoglobin (HbA1c), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) levels, as well as aldose reductase (AR) activities, in brain tissue and serum were determined. Electron microscopy was used to observe neuron and vessel changes in the brain. In STZ‑treated rats, blood glucose, low density lipoproteins, triglycerides and total cholesterol levels increased 1.43‑3.0‑fold and high density lipoprotein, HbA1c and insulin sensitivity index increased 1.1‑1.23‑fold compared with control. At week 16 following treatment, DM rat serum H2O2 concentration was increased, indicating oxidative stress and mRNA levels of GPx and SOD were 2‑fold higher than the control. Protein GPx and SOD levels were reduced (PNeuron cells and blood vessels in the DM rat brains became increasingly abnormal over time with altered Golgi bodies, mitochondria and endoplasmic reticulum cisterns, concurrent with SOD inactivation and AR protein accumulation. Disease progression in rats with STZ‑induced DM included brain pathologies with vascular and neuron cell abnormalities, associated with the reduction of SOD, CAT and GPx activities and also AR accumulation.

  1. Non-gated vessel wall imaging of the internal carotid artery using radial scanning and fast spin echo sequence. Evaluation of vessel signal intensity by flow rate at 3.0 tesla

    International Nuclear Information System (INIS)

    Nakamura, Manami; Makabe, Takeshi; Ichikawa, Masaki; Hatakeyama, Ryohei; Sugimori, Hiroyuki; Sakata, Motomichi

    2013-01-01

    Vessel wall imaging using radial scanning does not use a blood flow suppression pulse with gated acquisition. It has been proposed that there may not be a flow void effect if the flow rate is slow; however, this has yet to be empirically tested. To clarify the relationship between the signal intensity of the vessel lumen and the blood flow rate in a flow phantom, we investigated the usefulness of vessel wall imaging at 3.0 tesla (T). We measured the signal intensity while changing the flow rate in the flow phantom. Radial scanning at 1.5 T showed sufficient flow voids at above medium flow rates. There was no significant difference in lumen signal intensity at the carotid artery flow rate. The signal intensity of the vessel lumen decreased sufficiently using the radial scan method at 3.0 T. We thus obtained sufficient flow void effects at the carotid artery flow rate. We conclude this technique to be useful for evaluating plaque if high contrast can be maintained for fixed tissue (such as plaque) and the vessel lumen. (author)

  2. Combining endoscopes with PIV and digital holography for the study of vessel model mechanics

    International Nuclear Information System (INIS)

    Arévalo, Laura; Palero, Virginia; Andrés, Nieves; Arroyo, M P; Lobera, Julia

    2015-01-01

    In this work traditional fluid and solid mechanics measurement techniques have been combined with endoscopes for the study of blood vessel models’ mechanical properties. Endoscopes have been used as the imaging part of a high-speed PIV system to obtain the velocity field in a vessel model immersed in a container with a refractive index-matching liquid. In this way, we take advantage of the fact that the endoscope tip can be immersed in liquid. Endoscopes have also been used as the imaging and illuminating part of a digital holographic set-up for wall deformation measurement. The novelty of this work is that only one endoscope was used for illuminating and observing the vessel model, using the endoscope’s own illuminating system as the illumination source. The performance of endoscopes in different vessel models has been tested. The results of flow velocity and wall deformation in the different blood vessel models are presented. (paper)

  3. Correlations Between the Density of Tryptase Positive Mast Cells (DMCT and that of New Blood Vessels (CD105+ in Patients with Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Micu Gianina Viorica

    2016-06-01

    Full Text Available Mast cells proteases, tryptase and chymase are directly involved in the growth and progression of solid tumors due to their important role in tumor angiogenesis. We examined the density of tryptase positive mast cells and the mean density of new blood vessels in gastric malignant tumors of patients with and without Helicobacter pylori infection, using immunohistochemical staining for tryptase (for mast cells and CD 105 (for new vessels. Tryptase and CD 105 expression was detected in gastrectomy specimens. In this study, mast cell density correlates with angiogenesis and the growth and progression of gastric cancer. It also shows that the participation of Helicobacter pylori infection in the growth and progress of gastric neoplasia is due to an increase of peritumoral angiogenesis, with subsequent local and distant tumor spread and perivascular growth, but without perineural and nodal involvement.

  4. Mechanism of /sup 67/Ga uptake by an experimental abscess. Permeability of plasma from blood vessel in abscess

    Energy Technology Data Exchange (ETDEWEB)

    Nitta, Kazuo; Ogawa, Hiroshi; Ando, Atsushi; Ando, Itsuko; Hiraki, Tatsunosuke; Hisada, Kinichi

    1985-06-01

    In the previous paper, we reported that /sup 67/Ga was accumulated in abscess and uptake rate of /sup 67/Ga in abscess increased with time after the injection of /sup 67/Ga-citrate. The present study was undertaken to elucidate the influence of blood flow on the accumulation of /sup 67/Ga in abscess. Five days after subcutaneous injection of 0.2 ml of turpentine to the rats, /sup 131/I-human serum albumin (HSA) was injected intravenously to the rats. At an appropriate time after the injection (10 min to 6 days), uptake rates of /sup 131/I-HSA in abscess and normal tissues were measured. Similarly, /sup 51/Cr-red blood cells (RBC) were injected intravenously to the above rats and the uptake rates of /sup 51/Cr-RBC were also measured. One, three, and 24 hours after injection of /sup 131/I-HSA, the uptake rates of /sup 131/I-HSA in abscess were 1.32 %dose/g, 1.84 %dose/g, and 0.82 %dose/g, respectively. However, the uptake rates of /sup 51/Cr-RBC in abscess was very small, and the value was 0.14 %dose/g at 24 hours after the injection. In the case of abscess, blood in the tissue fluid was very little, but the permeability of /sup 131/I-HSA from the blood vessel in the tissue was much larger than that of normal tissues. From these facts, it was deduced that the accelerated permeability caused the abscess accumulation of /sup 67/Ga.

  5. IMPROVING THE QUALITY OF NEAR-INFRARED IMAGING OF IN VIVOBLOOD VESSELS USING IMAGE FUSION METHODS

    DEFF Research Database (Denmark)

    Jensen, Andreas Kryger; Savarimuthu, Thiusius Rajeeth; Sørensen, Anders Stengaard

    2009-01-01

    We investigate methods for improving the visual quality of in vivo images of blood vessels in the human forearm. Using a near-infrared light source and a dual CCD chip camera system capable of capturing images at visual and nearinfrared spectra, we evaluate three fusion methods in terms...... of their capability of enhancing the blood vessels while preserving the spectral signature of the original color image. Furthermore, we investigate a possibility of removing hair in the images using a fusion rule based on the "a trous" stationary wavelet decomposition. The method with the best overall performance...... with both speed and quality in mind is the Intensity Injection method. Using the developed system and the methods presented in this article, it is possible to create images of high visual quality with highly emphasized blood vessels....

  6. Reducing the data: Analysis of the role of vascular geometry on blood flow patterns in curved vessels

    Science.gov (United States)

    Alastruey, Jordi; Siggers, Jennifer H.; Peiffer, Véronique; Doorly, Denis J.; Sherwin, Spencer J.

    2012-03-01

    Three-dimensional simulations of blood flow usually produce such large quantities of data that they are unlikely to be of clinical use unless methods are available to simplify our understanding of the flow dynamics. We present a new method to investigate the mechanisms by which vascular curvature and torsion affect blood flow, and we apply it to the steady-state flow in single bends, helices, double bends, and a rabbit thoracic aorta based on image data. By calculating forces and accelerations in an orthogonal coordinate system following the centreline of each vessel, we obtain the inertial forces (centrifugal, Coriolis, and torsional) explicitly, which directly depend on vascular curvature and torsion. We then analyse the individual roles of the inertial, pressure gradient, and viscous forces on the patterns of primary and secondary velocities, vortical structures, and wall stresses in each cross section. We also consider cross-sectional averages of the in-plane components of these forces, which can be thought of as reducing the dynamics of secondary flows onto the vessel centreline. At Reynolds numbers between 50 and 500, secondary motions in the directions of the local normals and binormals behave as two underdamped oscillators. These oscillate around the fully developed state and are coupled by torsional forces that break the symmetry of the flow. Secondary flows are driven by the centrifugal and torsional forces, and these are counterbalanced by the in-plane pressure gradients generated by the wall reaction. The viscous force primarily opposes the pressure gradient, rather than the inertial forces. In the axial direction, and depending on the secondary motion, the curvature-dependent Coriolis force can either enhance or oppose the bulk of the axial flow, and this shapes the velocity profile. For bends with little or no torsion, the Coriolis force tends to restore flow axisymmetry. The maximum circumferential and axial wall shear stresses along the centreline

  7. Perfusion by Arterial Spin labelling following Single dose Tadalafil In Small vessel disease (PASTIS)

    DEFF Research Database (Denmark)

    Pauls, Mathilde M H; Clarke, Natasha; Trippier, Sarah

    2017-01-01

    vascular territories. The aim of this trial is to test the hypothesis that tadalafil increases cerebral blood flow in older people with small vessel disease. METHODS/DESIGN: Perfusion by Arterial Spin labelling following Single dose Tadalafil In Small vessel disease (PASTIS) is a phase II randomised double......-blind crossover trial. In two visits, 7-30 days apart, participants undergo arterial spin labelling to measure cerebral blood flow and a battery of cognitive tests, pre- and post-dosing with oral tadalafil (20 mg) or placebo. SAMPLE SIZE: 54 participants are required to detect a 15% increase in cerebral blood...

  8. Vasoactive receptors in abdominal blood vessels of the dogfish shark, Squalus acanthias.

    Science.gov (United States)

    Evans, D H

    2001-01-01

    Previous studies have demonstrated that the ventral aorta of the dogfish shark, Squalus acanthias, responds to a variety of cell-signaling agents. To investigate the generality of vasoactive receptors in the shark vasculature, in particular a conductance artery (anterior mesenteric) and vein (posterior intestinal), I measured the effect of acetylcholine, endothelin, nitric oxide, natriuretic peptides, and prostaglandins on tension in isolated rings from these vessels. Both vessels responded to these agents, and responses to receptor-specific ligands for endothelin and natriuretic peptide receptors suggest that B-type endothelin receptors are expressed in both vessels and that the artery expresses both A- and B-type natriuretic peptide receptors; however, the vein (like the ventral aorta) expresses only the B-type natriuretic peptide receptor. My data suggest that a suite of signaling systems is ubiquitous in both arteries and veins in at least this elasmobranch species. Their role in hemodynamics and osmoregulation (perfusion of gill and rectal gland) remains to be determined.

  9. Barriers to franchise initiation for general remodelers in U.S. remodeling industry: A non-franchisor perspective

    OpenAIRE

    Murray, B. C.

    2008-01-01

    The following report is an exploratory investigation into the barriers of franchise initiation for general contractors in the US remodeling industry. The applicability of theories used to describe why firms franchise is evaluated using secondary quantitative data. Further exploration is achieved by interviewing non-franchising, general remodelers classified as 'potential franchisors'. Overall, the outcomes suggest that franchisee recruitment is a perceived operational barrier by general remod...

  10. Human Albumin Improves Long-Term Behavioral Sequelae After Subarachnoid Hemorrhage Through Neurovascular Remodeling.

    Science.gov (United States)

    Xie, Yi; Liu, Wenhua; Zhang, Xiaohao; Wang, Liumin; Xu, Lili; Xiong, Yunyun; Yang, Lian; Sang, Hongfei; Ye, Ruidong; Liu, Xinfeng

    2015-10-01

    Subarachnoid hemorrhage results in significant long-lasting neurologic sequelae. Here, we investigated whether human albumin improves long-term outcomes in experimental subarachnoid hemorrhage and whether neurovascular remodeling is involved in the protection of albumin. Laboratory investigation. Hospital research laboratory. Male Sprague-Dawley rats. Rats underwent subarachnoid hemorrhage by endovascular perforation. Albumin of either 0.63 or 1.25 g/kg was injected IV immediately after the surgery. Modified Garcia test, beam-walking test, novel object recognition, and Morris water maze were employed to determine the behavioral deficits. The effects of albumin on early neurovascular dysfunction and chronic synaptic plasticity were also studied. Both doses of albumin significantly improved the sensorimotor scores (F = 31.277; p = 0.001) and cognitive performance (F = 7.982; p = 0.001 in novel object recognition test; and F = 3.431; p = 0.026 in the latency analysis of Morris water maze test) for at least 40 days after subarachnoid hemorrhage. There were remarkable microvasculature hypoperfusion, intracranial pressure rise, early vasoconstriction, neural apoptosis, and degeneration in subarachnoid hemorrhage rats, with albumin significantly attenuating such neurovascular dysfunction. Furthermore, albumin markedly prevented blood-brain barrier disruption, as indicated by less blood-brain barrier leakage, preserved blood-brain barrier-related proteins, and dampened gelatinase activities. The expressions of key synaptic elements were up-regulated with albumin supplementation in both acute and chronic phases. Accordingly, a higher dendritic spine density was observed in the prefrontal and hippocampal areas of albumin-treated subarachnoid hemorrhage animals. Albumin at low-to-moderate doses markedly improves long-term neurobehavioral sequelae after subarachnoid hemorrhage, which may involve an integrated process of neurovascular remodeling.

  11. Estrogen therapy may counterbalance eutrophic remodeling of coronary arteries and increase bradykinin relaxation in a rat model of menopausal hypertension.

    Science.gov (United States)

    Matrai, Mate; Hetthéssy, Judit R; Nadasy, Gyorgy L; Szekacs, Bela; Mericli, Metin; Acs, Nandor; Monos, Emil; Arbib, Nissim; Varbiro, Szabolcs

    2016-07-01

    Hypertension causes adverse remodeling and vasomotor alterations in coronaries. Hormones such as estrogen may help counterbalance some of these effects. The aim of this study was to analyze the effects of ovariectomy and estrogen therapy in a rat model of menopausal hypertension induced by angiotensin II (AII). We investigated diameter, tone, and mechanics of intramural coronaries taken from ovariectomized female rats (n = 11) that received chronic AII treatment to induce hypertension, and compared the results with those found in female rats that were also given estrogen therapy (n = 11). The "hypertensive control" group (n = 11) underwent an abdominal sham operation, and received AII. After 4 weeks of AII treatment, side branches of left anterior descendent coronary (approximately 200 μm in diameter) were isolated, cannulated with plastic microcannulas at both ends, and studied in vitro in a vessel chamber. The inner and outer diameter of the arteries were measured by microangiometry, and spontenuous tone, wall thickness, wall cross-sectional area, tangential stress, incremental distensibility, circumferential incremental elastic modulus, thromboxane agonist-induced tone, and bradykinin-induced dilation were calculated. In hypertension, intramural small coronaries show inward eutrophic remodeling after ovariectomy comparing with hypertensive controls. Estrogen therapy had an opposite effect on vessel diameter. Hormone therapy led to an increase in spontaneous tone, allowing for greater dilatative capacity. Estrogen may therefore be considered to counterbalance some of the adverse changes seen in the wall of intramural coronaries in the early stages of chronic hypertension.

  12. A Review of Algorithms for Retinal Vessel Segmentation

    Directory of Open Access Journals (Sweden)

    Monserrate Intriago Pazmiño

    2014-10-01

    Full Text Available This paper presents a review of algorithms for extracting blood vessels network from retinal images. Since retina is a complex and delicate ocular structure, a huge effort in computer vision is devoted to study blood vessels network for helping the diagnosis of pathologies like diabetic retinopathy, hypertension retinopathy, retinopathy of prematurity or glaucoma. To carry out this process many works for normal and abnormal images have been proposed recently. These methods include combinations of algorithms like Gaussian and Gabor filters, histogram equalization, clustering, binarization, motion contrast, matched filters, combined corner/edge detectors, multi-scale line operators, neural networks, ants, genetic algorithms, morphological operators. To apply these algorithms pre-processing tasks are needed. Most of these algorithms have been tested on publicly retinal databases. We have include a table summarizing algorithms and results of their assessment.

  13. Chromatin remodelling: the industrial revolution of DNA around histones.

    Science.gov (United States)

    Saha, Anjanabha; Wittmeyer, Jacqueline; Cairns, Bradley R

    2006-06-01

    Chromatin remodellers are specialized multi-protein machines that enable access to nucleosomal DNA by altering the structure, composition and positioning of nucleosomes. All remodellers have a catalytic ATPase subunit that is similar to known DNA-translocating motor proteins, suggesting DNA translocation as a unifying aspect of their mechanism. Here, we explore the diversity and specialization of chromatin remodellers, discuss how nucleosome modifications regulate remodeller activity and consider a model for the exposure of nucleosomal DNA that involves the use of directional DNA translocation to pump 'DNA waves' around the nucleosome.

  14. AN EFFICIENT TECHNIQUE FOR RETINAL VESSEL SEGMENTATION AND DENOISING USING MODIFIED ISODATA AND CLAHE

    Directory of Open Access Journals (Sweden)

    Khan Bahadar Khan

    2016-11-01

    Full Text Available Retinal damage caused due to complications of diabetes is known as Diabetic Retinopathy (DR. In this case, the vision is obscured due to the damage of retinal tinny blood vessels of the retina. These tinny blood vessels may cause leakage which affect the vision and can lead to complete blindness. Identification of these new retinal vessels and their structure is essential for analysis of DR. Automatic blood vessels segmentation plays a significant role to assist subsequent automatic methodologies that aid to such analysis. In literature most of the people have used computationally hungry a strong preprocessing steps followed by a simple thresholding and post processing, But in our proposed technique we utilize an arrangement of  light pre-processing which consists of Contrast Limited Adaptive Histogram Equalization (CLAHE for contrast enhancement, a difference image of green channel from its Gaussian blur filtered image to remove local noise or geometrical object, Modified Iterative Self Organizing Data Analysis Technique (MISODATA for segmentation of vessel and non-vessel pixels based on global and local thresholding, and a strong  post processing using region properties (area, eccentricity to eliminate the unwanted region/segment, non-vessel pixels and noise that never been used to reject misclassified foreground pixels. The strategy is tested on the publically accessible DRIVE (Digital Retinal Images for Vessel Extraction and STARE (STructured Analysis of the REtina databases. The performance of proposed technique is assessed comprehensively and the acquired accuracy, robustness, low complexity and high efficiency and very less computational time that make the method an efficient tool for automatic retinal image analysis. Proposed technique perform well as compared to the existing strategies on the online available databases in term of accuracy, sensitivity, specificity, false positive rate, true positive rate and area under receiver

  15. Luteolin Ameliorates Hypertensive Vascular Remodeling through Inhibiting the Proliferation and Migration of Vascular Smooth Muscle Cells

    Directory of Open Access Journals (Sweden)

    Jie Su

    2015-01-01

    Full Text Available Objectives. Preliminary researches showed that luteolin was used to treat hypertension. However, it is still unclear whether luteolin has effect on the hypertensive complication such as vascular remodeling. The present study was designed to investigate the effect of luteolin on the hypertensive vascular remodeling and its molecular mechanism. Method and Results. We evaluated the effect of luteolin on aorta thickening of hypertension in spontaneous hypertensive rats (SHRs and found that luteolin could significantly decrease the blood pressure and media thickness of aorta in vivo. Luteolin could inhibit angiotensin II- (Ang II- induced proliferation and migration of vascular smooth muscle cells (VSMCs. Dichlorofluorescein diacetate (DCFH-DA staining result showed that luteolin reduced Ang II-stimulated ROS production in VSMCs. Furthermore, western blot and gelatin zymography results showed that luteolin treatment leaded to a decrease in ERK1/2, p-ERK1/2, p-p38, MMP2, and proliferating cell nuclear antigen (PCNA protein level. Conclusion. These data support that luteolin can ameliorate hypertensive vascular remodeling by inhibiting the proliferation and migration of Ang II-induced VSMCs. Its mechanism is mediated by the regulation of MAPK signaling pathway and the production of ROS.

  16. Extravasal occlusion of large vessels with titanic clips: efficiency, indications, and contraindications.

    Science.gov (United States)

    Vasilenko, Yu V; Kim, A I; Kotov, S A

    2002-11-01

    The mechanism of extravasal occlusion of blood vessels with titanic clips "Atrauclip" and "Ligaclip extra" was studied in order to reveal indications and contraindications to their use. Occlusion with the clips of both types was ineffective in vessels with a diameter of >7.0 mm. Arteritis or the presence of an intravascular occlusion facility in the vessel were also the contraindications for clip occlusion. In overcases the procedure of occlusion with titanic clips was efficient and atraumatic.

  17. Open Craniosynostosis Surgery: Effect of Early Intraoperative Blood Transfusion on Postoperative Course.

    Science.gov (United States)

    Kurnik, Nicole M; Bristol, Ruth; Maneri, Celia; Singhal, Raj; Singh, Davinder J

    2017-07-01

    Correction of craniosynostosis can result in blood loss when the patient already has physiologic anemia. The aim of this study was to determine whether patients benefit from early blood transfusion and whether the timing of blood transfusion affects metabolic disturbances and the postoperative course. In this retrospective review, 71 patients who underwent open calvarial vault remodeling for correction of craniosynostosis were separated into 2 groups according to whether they received blood transfusions early (within the first 30 minutes of surgery) or later (after the first 30 minutes of surgery). Patients were further separated into nonsyndromic and syndromic cohorts. Tracked variables included hemoglobin, hematocrit, arterial blood gas values, lactate level, length of stay, estimated blood loss, and amount of blood transfused in the operating room, amount transfused postoperatively, and total amount transfused.Among all patients, the early transfusion group had a higher hemoglobin nadir overall and received less postoperative blood. Within the nonsyndromic cohort, the early transfusion group had a higher estimated blood loss and received more transfused blood. In the syndromic cohort, the early transfusion group had a hemoglobin nadir that was significantly higher than in the late transfusion group and a lower estimated blood loss, shorter pediatric intensive care unit stay, and less postoperative blood transfused. Syndromic patients also received significantly more blood overall. For syndromic patients undergoing open calvarial vault remodeling, transfusion within the first 30 minutes of surgery should be considered.

  18. Hybrid Segmentation of Vessels and Automated Flow Measures in In-Vivo Ultrasound Imaging

    DEFF Research Database (Denmark)

    Moshavegh, Ramin; Martins, Bo; Hansen, Kristoffer Lindskov

    2016-01-01

    Vector Flow Imaging (VFI) has received an increasing attention in the scientific field of ultrasound, as it enables angle independent visualization of blood flow. VFI can be used in volume flow estimation, but a vessel segmentation is needed to make it fully automatic. A novel vessel segmentation...

  19. Careful treatment planning enables safe ablation of liver tumors adjacent to major blood vessels by percutaneous irreversible electroporation (IRE).

    Science.gov (United States)

    Kos, Bor; Voigt, Peter; Miklavcic, Damijan; Moche, Michael

    2015-09-01

    Irreversible electroporation (IRE) is a tissue ablation method, which relies on the phenomenon of electroporation. When cells are exposed to a sufficiently electric field, the plasma membrane is disrupted and cells undergo an apoptotic or necrotic cell death. Although heating effects are known IRE is considered as non-thermal ablation technique and is currently applied to treat tumors in locations where thermal ablation techniques are contraindicated. The manufacturer of the only commercially available pulse generator for IRE recommends a voltage-to-distance ratio of 1500 to 1700 V/cm for treating tumors in the liver. However, major blood vessels can influence the electric field distribution. We present a method for treatment planning of IRE which takes the influence of blood vessels on the electric field into account; this is illustrated on a treatment of 48-year-old patient with a metastasis near the remaining hepatic vein after a right side hemi-hepatectomy. Output of the numerical treatment planning method shows that a 19.9 cm3 irreversible electroporation lesion was generated and the whole tumor was covered with at least 900 V/cm. This compares well with the volume of the hypodense lesion seen in contrast enhanced CT images taken after the IRE treatment. A significant temperature raise occurs near the electrodes. However, the hepatic vein remains open after the treatment without evidence of tumor recurrence after 6 months. Treatment planning using accurate computer models was recognized as important for electrochemotherapy and irreversible electroporation. An important finding of this study was, that the surface of the electrodes heat up significantly. Therefore the clinical user should generally avoid placing the electrodes less than 4 mm away from risk structures when following recommendations of the manufacturer.

  20. Cell Matrix Remodeling Ability Shown by Image Spatial Correlation

    Science.gov (United States)

    Chiu, Chi-Li; Digman, Michelle A.; Gratton, Enrico

    2013-01-01

    Extracellular matrix (ECM) remodeling is a critical step of many biological and pathological processes. However, most of the studies to date lack a quantitative method to measure ECM remodeling at a scale comparable to cell size. Here, we applied image spatial correlation to collagen second harmonic generation (SHG) images to quantitatively evaluate the degree of collagen remodeling by cells. We propose a simple statistical method based on spatial correlation functions to determine the size of high collagen density area around cells. We applied our method to measure collagen remodeling by two breast cancer cell lines (MDA-MB-231 and MCF-7), which display different degrees of invasiveness, and a fibroblast cell line (NIH/3T3). We found distinct collagen compaction levels of these three cell lines by applying the spatial correlation method, indicating different collagen remodeling ability. Furthermore, we quantitatively measured the effect of Latrunculin B and Marimastat on MDA-MB-231 cell line collagen remodeling ability and showed that significant collagen compaction level decreases with these treatments. PMID:23935614

  1. In silico particle margination in blood flow

    OpenAIRE

    Müller, Kathrin

    2015-01-01

    A profound knowledge of margination, the migration of blood components to the vessel wall in blood flow, is required in order to understand the genesis of various diseases, as e.g., cardiovascular diseases or bleeding disorders. Margination of particles is a pre-condition for potential adhesion. Adhesion to the vessel wall is required for platelets, the protein von Willebrand factor (VWF), but also for drug and imaging agent carriers in order to perform their particular tasks. In the haemosta...

  2. Tumor vessel normalization by the PI3K inhibitor HS-173 enhances drug delivery.

    Science.gov (United States)

    Kim, Soo Jung; Jung, Kyung Hee; Son, Mi Kwon; Park, Jung Hee; Yan, Hong Hua; Fang, Zhenghuan; Kang, Yeo Wool; Han, Boreum; Lim, Joo Han; Hong, Soon-Sun

    2017-09-10

    Tumor vessels are leaky and immature, which causes poor oxygen and nutrient supply to tumor vessels and results in cancer cell metastasis to distant organs. This instability of tumor blood vessels also makes it difficult for anticancer drugs to penetrate and reach tumors. Numerous tumor vessel normalization approaches have been investigated for improving drug delivery into tumors. In this study, we investigated whether phosphoinositide 3-kinase (PI3K) inhibitors are able to improve vascular structure and function over the prolonged period necessary to achieve effective vessel normalization. The PI3K inhibitors, HS-173 and BEZ235 potently suppressed tumor growth and hypoxia, and increased tumor apoptosis in animal models. PI3K inhibitors also induced a regular, flat monolayer of endothelial cells (ECs) in vessels, improving stability of vessel structure, and normalized tumor vessels by increasing vascular maturity, pericyte coverage, basement membrane thickness, and tight-junctions. These effects resulted in a decrease in tumor vessel tortuosity and vessel thinning, and improved vessel function and blood flow. The tumor vessel stabilization effect of the PI3K inhibitor HS-173 also decreased the number of metastatic lung nodules in vivo metastasis model. Furthermore, HS-173 improved the delivery of doxorubicin into the tumor region, enhancing its anticancer effects. Mechanistic studies suggested that PI3K inhibitor HS-173-induced vessel normalization reflected changes in endothelial Notch signaling. Taken together, our findings indicate that vessel normalization by PI3K inhibitors restrained tumor growth and metastasis while improving chemotherapy by enhancing drug delivery into the tumor, suggesting that HS-173 may have a therapeutic value as an enhancer or an anticancer drug. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Effect of melatonin, captopril, spironolactone and simvastatin on blood pressure and left ventricular remodelling in spontaneously hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Šimko, F.; Pecháňová, Olga; Pelouch, Václav; Krajčírovičová, K.; Müllerová, M.; Bednárová, K.; Adamcová, M.; Paulis, L.

    2009-01-01

    Roč. 27, Suppl.6 (2009), S5-S10 ISSN 0263-6352 R&D Projects: GA ČR GA305/09/0336 Institutional research plan: CEZ:AV0Z50110509 Keywords : cardiac hypertrophy * fibrosis * ventricular remodeling Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 4.988, year: 2009

  4. Direct bolus imaging of cervical blood vessels by means of MRI

    International Nuclear Information System (INIS)

    Satoh, Toshihiko; Fujioka, Mutsuhisa; Watari, Tsutomu; Nishimura, Gen; Matsumoto, Toshihiko; Washiya, Sumio; Inoue, Kiyoshi; Horita, Masatoshi; Shimizu, Kohji.

    1991-01-01

    Direct bolus imaging (DBI) is one of the non-invasive method for flow measurements which is based on the bolus tracking technique. DBI permits the direct visualization of flow velocity profiles and vessel band width. We performed screening for cervical vessel disease in patients with vertigo by means of DBI. MR system used here was 0.5 T superconducting imager-SMT-50A (Shimazu Co. Ltd). Pulse sequence parameters were TR= 60 ms, TE= 50 ms, NEX= 1, acquisition matrix; 128 x 256, slice thickness= 5 mm, with cardiac gating. Pulse sequence employed a slice selective RF pulse at the level of C5 vertebral body to tag a disk of fluid perpendicular to the direction of flow, followed by a gradient reforcussed echo. We evaluated each peak high and band width of the common-carotid arteries and the vertebral arteries. Seventy nine of 83 cases had optimal examinations. Abnormal findings of DBI were seen in 15 of 79 cases, (including 2 of subclavian steal syndrome, 1 of carotid obstruction, 5 of vertebral obstruction, 1 of basilar artery obstruction, and 6 of hypoplasia of vertebral artery). The abnormal findings of DBI were well correlated with those of angiographic examinations. We concluded that DBI was suitable to the screening for cervical vessel diseases in patients with vertigo, and should be added to the routine MR studies. (author)

  5. Investigation of the blood behaviour and vascular diseases by using mathematical physic principles

    Science.gov (United States)

    Yardimci, Ahmet; Simsek, Buket

    2017-07-01

    In this paper we prepare a short survey for using of mathematical physic principles in blood flow and vascular diseases researches. The study of the behavior of blood flow in the blood vessels provides understanding on connection between flow and the development of dieseases such as atherosclerosis, thrombosis, aneurysms etc. and how the flow dynamics is changed under these conditions. Blood flow phenomena are often too complex that it would be possible to describe them entirely analytically, although simple models, such as Poiseuille model, can still provide some insight into blood flow. Blood is not an "ideal fluid" and energy is lost as flowing blood overcomes resistance. Resistance to blood flow is a function of viscosity, vessel radius, and vessel length. So, mathematical Physic principles are useful tools for blood flow research studies. Blood flow is a function of pressure gradient and resistance and resistance to flow can be estimates using Poiseuille's law. Reynold's number can be used to determine whether flow is laminar or turbulent.

  6. Evaluation of Peripheral Blood Circulation Disorder in Scleroderma Patients Using an Optical Sensor with a Pressurization Mechanism.

    Directory of Open Access Journals (Sweden)

    Yoshiki Yamakoshi

    Full Text Available Blood circulation function of peripheral blood vessels in skin dermis was evaluated employing an optical sensor with a pressurization mechanism using the blood outflow and reflow characteristics. The device contains a light source and an optical sensor. When applied to the skin surface, it first exerts the primary pressure (higher than the systolic blood pressure, causing an outflow of blood from the dermal peripheral blood vessels. After two heartbeats, the pressure is lowered (secondary pressure and blood reflows into the peripheral blood vessels. Hemoglobin concentration, which changes during blood outflow and reflow, is derived from the received light intensity using the Beer-Lambert law. This method was evaluated in 26 healthy female volunteers and 26 female scleroderma patients. In order to evaluate the blood circulation function of the peripheral blood vessels of scleroderma patients, pressurization sequence which consists of primary pressure followed by secondary pressure was adopted. Blood reflow during the first heartbeat period after applying the secondary pressure of 40mmHg was (mean±SD 0.059±0.05%mm for scleroderma patients and 0.173±0.104%mm for healthy volunteers. Blood reflow was significantly lower in scleroderma patients than in healthy volunteers (p<0.05. This result indicates that the information necessary for assessing blood circulation disorder of peripheral blood vessels in scleroderma patients is objectively obtained by the proposed method.

  7. Hypercholesterolemia induced cerebral small vessel disease.

    Science.gov (United States)

    Kraft, Peter; Schuhmann, Michael K; Garz, Cornelia; Jandke, Solveig; Urlaub, Daniela; Mencl, Stine; Zernecke, Alma; Heinze, Hans-Jochen; Carare, Roxana O; Kleinschnitz, Christoph; Schreiber, Stefanie

    2017-01-01

    While hypercholesterolemia plays a causative role for the development of ischemic stroke in large vessels, its significance for cerebral small vessel disease (CSVD) remains unclear. We thus aimed to understand the detailed relationship between hypercholesterolemia and CSVD using the well described Ldlr-/- mouse model. We used Ldlr-/- mice (n = 16) and wild-type (WT) mice (n = 15) at the age of 6 and 12 months. Ldlr-/- mice develop high plasma cholesterol levels following a high fat diet. We analyzed cerebral capillaries and arterioles for intravascular erythrocyte accumulations, thrombotic vessel occlusions, blood-brain barrier (BBB) dysfunction and microbleeds. We found a significant increase in the number of erythrocyte stases in 6 months old Ldlr-/- mice compared to all other groups (P hypercholesterolemia is related to a thrombotic CSVD phenotype, which is different from hypertension-related CSVD that associates with a hemorrhagic CSVD phenotype. Our data demonstrate a relationship between hypercholesterolemia and the development of CSVD. Ldlr-/- mice appear to be an adequate animal model for research into CSVD.

  8. Osteoblast recruitment routes in human cancellous bone remodeling

    DEFF Research Database (Denmark)

    Kristensen, Helene Bjørg; Andersen, Thomas Levin; Marcussen, Niels

    2014-01-01

    It is commonly proposed that bone forming osteoblasts recruited during bone remodeling originate from bone marrow perivascular cells, bone remodeling compartment canopy cells, or bone lining cells. However, an assessment of osteoblast recruitment during adult human cancellous bone remodeling...... is lacking. We addressed this question by quantifying cell densities, cell proliferation, osteoblast differentiation markers, and capillaries in human iliac crest biopsy specimens. We found that recruitment occurs on both reversal and bone-forming surfaces, as shown by the cell density and osterix levels...

  9. Skeletal nutrient vascular adaptation induced by external oscillatory intramedullary fluid pressure intervention

    Directory of Open Access Journals (Sweden)

    Qin Yi-Xian

    2010-03-01

    Full Text Available Abstract Background Interstitial fluid flow induced by loading has demonstrated to be an important mediator for regulating bone mass and morphology. It is shown that the fluid movement generated by the intramedullary pressure (ImP provides a source for pressure gradient in bone. Such dynamic ImP may alter the blood flow within nutrient vessel adjacent to bone and directly connected to the marrow cavity, further initiating nutrient vessel adaptation. It is hypothesized that oscillatory ImP can mediate the blood flow in the skeletal nutrient vessels and trigger vasculature remodeling. The objective of this study was then to evaluate the vasculature remodeling induced by dynamic ImP stimulation as a function of ImP frequency. Methods Using an avian model, dynamics physiological fluid ImP (70 mmHg, peak-peak was applied in the marrow cavity of the left ulna at either 3 Hz or 30 Hz, 10 minutes/day, 5 days/week for 3 or 4 weeks. The histomorphometric measurements of the principal nutrient arteries were done to quantify the arterial wall area, lumen area, wall thickness, and smooth muscle cell layer numbers for comparison. Results The preliminary results indicated that the acute cyclic ImP stimuli can significantly enlarge the nutrient arterial wall area up to 50%, wall thickness up to 20%, and smooth muscle cell layer numbers up to 37%. In addition, 3-week of acute stimulation was sufficient to alter the arterial structural properties, i.e., increase of arterial wall area, whereas 4-week of loading showed only minimal changes regardless of the loading frequency. Conclusions These data indicate a potential mechanism in the interrelationship between vasculature adaptation and applied ImP alteration. Acute ImP could possibly initiate the remodeling in the bone nutrient vasculature, which may ultimately alter blood supply to bone.

  10. Relationship of left ventricular, elastic and muscular arteries remodeling in patients with uncontrolled arterial hypertension

    Directory of Open Access Journals (Sweden)

    S. Ya. Dotsenko

    2013-04-01

    Full Text Available Introduction. Uncontrolled hypertension is observed in 65-92% of hypertensive patients. It plays an important role in the development of adverse cardiovascular events and survival, which depend on subclinical target organ damage. There are reports on the relationship between ineffective hypertension control and left ventricular (LV hypertrophy or large arteries stiffness. However, the nature of the remodeling in uncontrolled hypertension remains poorly understood. Objective: to study the character and relationship of left ventricular and arterial remodeling depending on effectiveness of hypertension control. Design and method. We performed a study of 363 hypertensive patients (160 men and 203 women aged 50,8 ± 1,2 years without comorbidities, which were divided into 3 groups according to the effectiveness of blood pressure (BP control: 160 patients with controlled hypertension, 142 patients with uncontrolled hypertension and 61 patients with resistant hypertension. Uncontrolled BP based on measured systolic BP≥140 mmHg and diastolic BP≥90 mmHg. Remodeling indexes of left ventricular, elastic (common carotid and muscular (brachial artery were evaluated by the ultrasonic method. The severity and character of diastolic dysfunction, hypertrophy, types of remodeling and stiffness were assessed. Statistical processing of the results was performed using Student's t criterion and Pearson correlation analysis. Results and discussion. According to the results of the study, uncontrolled hypertension affected the development of subclinical cardiovascular lesions negatively. Thus, LV hypertrophy was detected more frequently in the third group (91,8% in resistant hypertension versus 46,8% in controlled hypertension, p<0,05. Differences in LV geometry with increasing of concentric remodeling types were also observed more frequently in the third group, where concentric remodeling and concentric hypertrophy types were founded in 14,8% and 59

  11. Microscopical and elemental FESEM and Phenom ProX-SEM-EDS analysis of osteocyte- and blood vessel-like microstructures obtained from fossil vertebrates of the Eocene Messel Pit, Germany.

    Science.gov (United States)

    Cadena, Edwin

    2016-01-01

    The Eocene (∾48 Ma) Messel Pit in Germany is a UNESCO World Heritage Site because of its exceptionally preserved fossils, including vertebrates, invertebrates, and plants. Messel fossil vertebrates are typically characterized by their articulated state, and in some cases the skin, hair, feathers, scales and stomach contents are also preserved. Despite the exceptional macroscopic preservation of Messel fossil vertebrates, the microstructural aspect of these fossils has been poorly explored. In particular, soft tissue structures such as hair or feathers have not been chemically analyzed, nor have bone microstructures. I report here the preservation and recovery of osteocyte-like and blood vessel-like microstructures from the bone of Messel Pit specimens, including the turtles Allaeochelys crassesculpta and Neochelys franzeni, the crocodile Diplocynodon darwini, and the pangolin Eomanis krebsi. I used a Field Emission Scanning Electron Microscope (FESEM) and a Phenom ProX desktop scanning electron microscope (LOT-QuantumDesign) equipped with a thermionic CeB6 source and a high sensitivity multi-mode backscatter electron (BSE) for microscopical and elemental characterization of these bone microstructures. Osteocyte-like and blood vessel-like microstructures are constituted by a thin layer (∾50 nm thickness), external and internal mottled texture with slightly marked striations. Circular to linear marks are common on the external surface of the osteocyte-like microstructures and are interpreted as microbial troughs. Iron (Fe) is the most abundant element found in the osteocyte-like and blood vessel-like microstructures, but not in the bone matrix or collagen fibril-like microstructures. The occurrence of well-preserved soft-tissue elements (at least their physical form) establishes a promising background for future studies on preservation of biomolecules (proteins or DNA) in Messel Pit fossils.

  12. Microscopical and elemental FESEM and Phenom ProX-SEM-EDS analysis of osteocyte- and blood vessel-like microstructures obtained from fossil vertebrates of the Eocene Messel Pit, Germany

    Directory of Open Access Journals (Sweden)

    Edwin Cadena

    2016-01-01

    Full Text Available The Eocene (∾48 Ma Messel Pit in Germany is a UNESCO World Heritage Site because of its exceptionally preserved fossils, including vertebrates, invertebrates, and plants. Messel fossil vertebrates are typically characterized by their articulated state, and in some cases the skin, hair, feathers, scales and stomach contents are also preserved. Despite the exceptional macroscopic preservation of Messel fossil vertebrates, the microstructural aspect of these fossils has been poorly explored. In particular, soft tissue structures such as hair or feathers have not been chemically analyzed, nor have bone microstructures. I report here the preservation and recovery of osteocyte-like and blood vessel-like microstructures from the bone of Messel Pit specimens, including the turtles Allaeochelys crassesculpta and Neochelys franzeni, the crocodile Diplocynodon darwini, and the pangolin Eomanis krebsi. I used a Field Emission Scanning Electron Microscope (FESEM and a Phenom ProX desktop scanning electron microscope (LOT-QuantumDesign equipped with a thermionic CeB6 source and a high sensitivity multi-mode backscatter electron (BSE for microscopical and elemental characterization of these bone microstructures. Osteocyte-like and blood vessel-like microstructures are constituted by a thin layer (∾50 nm thickness, external and internal mottled texture with slightly marked striations. Circular to linear marks are common on the external surface of the osteocyte-like microstructures and are interpreted as microbial troughs. Iron (Fe is the most abundant element found in the osteocyte-like and blood vessel-like microstructures, but not in the bone matrix or collagen fibril-like microstructures. The occurrence of well-preserved soft-tissue elements (at least their physical form establishes a promising background for future studies on preservation of biomolecules (proteins or DNA in Messel Pit fossils.

  13. GPER activation ameliorates aortic remodeling induced by salt-sensitive hypertension.

    Science.gov (United States)

    Liu, Liu; Kashyap, Shreya; Murphy, Brennah; Hutson, Dillion D; Budish, Rebecca A; Trimmer, Emma H; Zimmerman, Margaret A; Trask, Aaron J; Miller, Kristin S; Chappell, Mark C; Lindsey, Sarah H

    2016-04-15

    The mRen2 female rat is an estrogen- and salt-sensitive model of hypertension that reflects the higher pressure and salt sensitivity associated with menopause. We previously showed that the G protein-coupled estrogen receptor (GPER) mediates estrogenic effects in this model. The current study hypothesized that GPER protects against vascular injury during salt loading. Intact mRen2 female rats were fed a normal (NS; 0.5% Na(+)) or high-salt diet (HS; 4% Na(+)) for 10 wk, which significantly increased systolic blood pressure (149 ± 5 vs. 224 ± 8 mmHg;PTreatment with the selective GPER agonist G-1 for 2 wk did not alter salt-sensitive hypertension (216 ± 4 mmHg;P> 0.05) or ex vivo vascular responses to angiotensin II or phenylephrine (P> 0.05). However, G-1 significantly attenuated salt-induced aortic remodeling assessed by media-to-lumen ratio (NS: 0.43; HS+veh: 0.89; HS+G-1: 0.61;P< 0.05). Aortic thickening was not accompanied by changes in collagen, elastin, or medial proliferation. However, HS induced increases in medial layer glycosaminoglycans (0.07 vs. 0.42 mm(2);P< 0.001) and lipid peroxidation (0.11 vs. 0.51 mm(2);P< 0.01), both of which were reduced by G-1 (0.20 mm(2)and 0.23 mm(2); both P< 0.05). We conclude that GPER's beneficial actions in the aorta of salt-loaded mRen2 females occur independently of changes in blood pressure and vasoreactivity. GPER-induced attenuation of aortic remodeling was associated with a reduction in oxidative stress and decreased accumulation of glycosaminoglycans. Endogenous activation of GPER may protect females from salt- and pressure-induced vascular damage. Copyright © 2016 the American Physiological Society.

  14. Impact of long-term burden of excessive adiposity and elevated blood pressure from childhood on adulthood left ventricular remodeling patterns: the Bogalusa Heart Study.

    Science.gov (United States)

    Lai, Chin-Chih; Sun, Dianjianyi; Cen, Ruiqi; Wang, Jian; Li, Shengxu; Fernandez-Alonso, Camilo; Chen, Wei; Srinivasan, Sathanur R; Berenson, Gerald S

    2014-10-14

    Cardiovascular risk factors are associated with left ventricular hypertrophy (LVH), but little is known regarding related impact of longitudinal measures of childhood adiposity and LV hemodynamic variables. The aim of this study was to examine the impact of cumulative long-term burden and trends of excessive adiposity and elevated blood pressure (BP) during childhood on adulthood LVH and LV geometric remodeling patterns. This longitudinal study consisted of 1,061 adults, age 24 to 46 years, who had been examined 4 or more times for body mass index (BMI) and BP starting in childhood, with a mean follow-up of 28.0 years. The area under the curve (AUC) was calculated as a measure of long-term burden (total AUC) and trends (incremental AUC) of BMI and BP from childhood to adulthood. Four LV geometric types were defined-normal, concentric remodeling (CR), eccentric hypertrophy (EH), and concentric hypertrophy (CH)-all on the basis of LV mass indexed for body height (m(2.7)) and relative wall thickness. Higher values of BMI and systolic and diastolic BP in childhood and adulthood, as well as total AUC and incremental AUC, were all significantly associated with higher LV mass index and LVH, adjusted for race, sex, and age. In addition, higher values of BMI and BP in childhood and adulthood, total AUC, and incremental AUC were significantly associated with EH and CH but not with CR. Importantly, all of these measures of BMI had a consistently and significantly greater influence on EH than did measures of BP. These findings indicate that the adverse influence of excessive adiposity and elevated BP levels on LVH begins in childhood. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  15. Fe3O4@ZnO core-shell nanocomposites for efficient and repetitive removal of low density lipoprotein in plasma and on blood vessel

    International Nuclear Information System (INIS)

    Huang, Xiao; Lu, Juan; Yue, Danyang; Fan, Yijuan; Yi, Caixia; Wang, Xiaoying; Zhang, Mengxue; Pan, Jun

    2015-01-01

    Low density lipoprotein (LDL)-apheresis therapy, which directly removes LDL from plasma by LDL-adsorbents in vitro is found to be clinically effective and safe to lower the LDL content in blood to prevent cardiovascular disease. Thus, developing excellent LDL adsorbents are becoming more and more attractive. Herein, functional Fe 3 O 4 @ZnO core–shell nanocomposites have been synthesized by a facile and eco-friendly two-step method. Not only do they possess high LDL adsorption (in PBS/plasma as well as on blood vessels) and favorable magnetic targeting ability but they can also be reused conveniently, which offer the Fe 3 O 4 @ZnO core–shell nanocomposites significant potential in the removal of LDL in vitro and in vivo. (paper)

  16. Effects of angiopoietin-1 on inflammatory injury in endothelial progenitor cells and blood vessels.

    Science.gov (United States)

    Wang, Yi-Qing; Song, Jing-Jin; Han, Xiao; Liu, Yi-Ye; Wang, Xi-Huang; Li, Zhi-Ming; Tzeng, Chi-Meng

    2014-01-01

    Endothelial progenitor cells (EPCs) and angiopoietin-1 (Ang-1) play important roles in vasculogenesis and angiogenesis, respectively. Thus, targeting both aspects of cardiovascular tissue regeneration may offer promising therapeutic options for cardiovascular disorders. To this end, we constructed a lentiviral vector (pNL) with the Ang-1 gene and transfected EPCs with it (Ang-1-EPCs) to investigate vasculogenesis in both cellular and animal models. Compared to controls, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) increased significantly in both untreated EPCs and in the pNL vector group. After Ang-1 transcription, ICAM-1 and VCAM-1 decreased considerably in those treatment groups. Ang-1-modified EPCs alleviated inflammatory responses induced by tumor-necrosis factor-α (TNF-α) in vitro. Moreover, Ang-1-EPC implantation inhibited neointimal hyperplasia after balloon catheter injury in rats, dramatically diminishing the intimal-media (I/M) ratio and decreasing the neointimal area. Proliferating cell nuclear antigen expression in the Ang-1-EPC group was lower than the EPC non-treatment group as well, suggesting that Ang-1-EPC improved cell survival during inflammation and promoted endothelialization in damaged blood vessels.

  17. The role of vasculature in bone development, regeneration and proper systemic functioning.

    Science.gov (United States)

    Filipowska, Joanna; Tomaszewski, Krzysztof A; Niedźwiedzki, Łukasz; Walocha, Jerzy A; Niedźwiedzki, Tadeusz

    2017-08-01

    Bone is a richly vascularized connective tissue. As the main source of oxygen, nutrients, hormones, neurotransmitters and growth factors delivered to the bone cells, vasculature is indispensable for appropriate bone development, regeneration and remodeling. Bone vasculature also orchestrates the process of hematopoiesis. Blood supply to the skeletal system is provided by the networks of arteries and arterioles, having distinct molecular characteristics and localizations within the bone structures. Blood vessels of the bone develop through the process of angiogenesis, taking place through different, bone-specific mechanisms. Impaired functioning of the bone blood vessels may be associated with the occurrence of some skeletal and systemic diseases, i.e., osteonecrosis, osteoporosis, atherosclerosis or diabetes mellitus. When a disease or trauma-related large bone defects appear, bone grafting or bone tissue engineering-based strategies are required. However, a successful bone regeneration in both approaches largely depends on a proper blood supply. In this paper, we review the most recent data on the functions, molecular characteristics and significance of the bone blood vessels, with a particular emphasis on the role of angiogenesis and blood vessel functioning in bone development and regeneration, as well as the consequences of its impairment in the course of different skeletal and systemic diseases.

  18. MR angiography of the cerebral vessels with inflow-increased visualization by overcontiguous imaging and advanced processing

    International Nuclear Information System (INIS)

    McLachian, S.; Simon, H.E.; de Graaf, R.; Ho, A.M.; Ruccio, W.J.; Steidley, J.W.; Pradhan, R.B.

    1989-01-01

    The purpose of this study was to increase the visualization of cerebral vessels with MR angiography by using an inflow technique from transverse sections. Difficulties with visualization include the tortuous nature of the vessels and slow blood flow. The MR method is a transverse two-dimensional multiple single-section sequence with a velocity-compensated gradient echo and presaturation. A S15 imager with 10-mTm gradients and a prototype angiographic package is used. Overcontiguous acquisition yields smaller effective center-to-center sections. Interpolation is used to generate interleaved plane projections. A combination of image parameter swill reduce the level of the stationary tissue relative to the flowing blood. For vessels that are not perpendicular to the section, overlapping the sections by 25%--33% is shown to reduce the staircase appearance without affecting the apparent size of the vessels. Interpolation of the MR images will further reduce this artifact, giving the vessels a smooth structure. MR angiography of the brain performed with an inflow technique allows the visualization of vessels in the brain even if the vessels follow tortuous paths. Presaturation and user-defined regions of interest can be used for ease of interpretation

  19. The chromatin remodeler SPLAYED regulates specific stress signaling pathways.

    Directory of Open Access Journals (Sweden)

    Justin W Walley

    2008-12-01

    Full Text Available Organisms are continuously exposed to a myriad of environmental stresses. Central to an organism's survival is the ability to mount a robust transcriptional response to the imposed stress. An emerging mechanism of transcriptional control involves dynamic changes in chromatin structure. Alterations in chromatin structure are brought about by a number of different mechanisms, including chromatin modifications, which covalently modify histone proteins; incorporation of histone variants; and chromatin remodeling, which utilizes ATP hydrolysis to alter histone-DNA contacts. While considerable insight into the mechanisms of chromatin remodeling has been gained, the biological role of chromatin remodeling complexes beyond their function as regulators of cellular differentiation and development has remained poorly understood. Here, we provide genetic, biochemical, and biological evidence for the critical role of chromatin remodeling in mediating plant defense against specific biotic stresses. We found that the Arabidopsis SWI/SNF class chromatin remodeling ATPase SPLAYED (SYD is required for the expression of selected genes downstream of the jasmonate (JA and ethylene (ET signaling pathways. SYD is also directly recruited to the promoters of several of these genes. Furthermore, we show that SYD is required for resistance against the necrotrophic pathogen Botrytis cinerea but not the biotrophic pathogen Pseudomonas syringae. These findings demonstrate not only that chromatin remodeling is required for selective pathogen resistance, but also that chromatin remodelers such as SYD can regulate specific pathways within biotic stress signaling networks.

  20. Vessel Enhancement and Segmentation of 4D CT Lung Image Using Stick Tensor Voting

    Science.gov (United States)

    Cong, Tan; Hao, Yang; Jingli, Shi; Xuan, Yang

    2016-12-01

    Vessel enhancement and segmentation plays a significant role in medical image analysis. This paper proposes a novel vessel enhancement and segmentation method for 4D CT lung image using stick tensor voting algorithm, which focuses on addressing the vessel distortion issue of vessel enhancement diffusion (VED) method. Furthermore, the enhanced results are easily segmented using level-set segmentation. In our method, firstly, vessels are filtered using Frangi's filter to reduce intrapulmonary noises and extract rough blood vessels. Secondly, stick tensor voting algorithm is employed to estimate the correct direction along the vessel. Then the estimated direction along the vessel is used as the anisotropic diffusion direction of vessel in VED algorithm, which makes the intensity diffusion of points locating at the vessel wall be consistent with the directions of vessels and enhance the tubular features of vessels. Finally, vessels can be extracted from the enhanced image by applying level-set segmentation method. A number of experiments results show that our method outperforms traditional VED method in vessel enhancement and results in satisfied segmented vessels.

  1. Hypertrophic remodeling of subcutaneous small resistance arteries in patients with Cushing's syndrome.

    Science.gov (United States)

    Rizzoni, Damiano; Porteri, Enzo; De Ciuceis, Carolina; Rodella, Luigi F; Paiardi, Silvia; Rizzardi, Nicola; Platto, Caterina; Boari, Gianluca E M; Pilu, Annamaria; Tiberio, Guido A M; Giulini, Stefano M; Favero, Gaia; Rezzani, Rita; Rosei, Claudia Agabiti; Bulgari, Giuseppe; Avanzi, Daniele; Rosei, Enrico Agabiti

    2009-12-01

    Structural alterations of small resistance arteries in essential hypertensive patients (EH) are mostly characterized by inward eutrophic remodeling. However, we observed hypertrophic remodeling in patients with renovascular hypertension, in those with acromegaly, as well as in patients with non-insulin-dependent diabetes mellitus, suggesting a relevant effect of humoral growth factors on vascular structure, even independent from the hemodynamic load. Cortisol may stimulate the renin-angiotensin system and may induce cardiac hypertrophy. However, presently no data are available about small artery structure in patients with Cushing's syndrome. We have investigated the structure of sc small resistance arteries in 12 normotensive subjects (NT), in 12 EH subjects, and in eight patients with Cushing's syndrome (CS). Small arteries from sc fat were dissected and mounted on a micromyograph. The normalized internal diameter, media thickness, media to lumen ratio, and the media cross-sectional area were measured, as well as indices of oxidative stress. Demographic variables were similar in the three groups, except for clinic blood pressure. The media to lumen ratio was significantly greater in EH and CS, compared with NT; no difference was observed between EH and CS. The media cross-sectional area was significantly greater in CS compared with EH and with NT. An increased vascular oxidative stress was present in CS, as demonstrated by increased levels of superoxide anions, cyclooxygenase-1 and endothelial nitric oxide synthase in the microvessels. Our results suggest the presence of hypertrophic remodeling in sc small resistance arteries of CS, probably as a consequence of growth-promoting properties of circulating cortisol and/or increased vascular oxidative stress.

  2. Hindlimb Suspension as a Model to Study Ophthalmic Complications in Microgravity Status Report: Optimization of Rat Retina Flat Mounts Staining to Study Vascular Remodeling

    Science.gov (United States)

    Theriot, Corey A.; Zanello, Susana B.

    2014-01-01

    Preliminary data from a prior tissue-sharing experiment has suggested that early growth response protein-1 (Egr1), a transcription factor involved in various stress responses in the vasculature, is induced in the rat retina after 14 days of hindlimb suspension (HS) and may be evidence that mechanical stress is occurring secondary to the cephalad fluid shift. This mechanical stress could cause changes in oxygenation of the retina, and the subsequent ischemia- or inflammation-driven hypoxia may lead to microvascular remodeling. This microvascular remodeling process can be studied using image analysis of retinal vessels and can be then be quantified by the VESsel GENeration Analysis (VESGEN) software, a computational tool that quantifies remodeling patterns of branching vascular trees and capillary or vasculogenic networks. Our project investigates whether rodent HS is a valid model to study the effects of simulated-weightlessness on ocular structures and their relationship with intracranial pressure (ICP). One of the hypotheses to be tested is that HS-induced cephalad fluid shift is accompanied by vascular engorgement that produces changes in retinal oxygenation, leading to oxidative stress, hypoxia, microvascular remodeling, and cellular degeneration. We have optimized the procedure to obtain flat mounts of rat retina, staining of the endothelial lining in vasculature and acquisition of high quality images suitable for VESGEN analysis. Briefly, eyes were fixed in 4% paraformaldehyde for 24 hours and retinas were detached and then mounted flat on microscope slides. The microvascular staining was done with endothelial cell-specific isolectin binding, coupled to Alexa-488 fluorophore. Image acquisition at low magnification and high resolution was performed using a new Leica SP8 confocal microscope in a tile pattern across the X,Y plane and multiple sections along the Z-axis. This new confocal microscope has the added capability of dye separation using the Linear

  3. The effect of adjuvant N-acetylcysteine effervescent tablets therapy on cardiopulmonary function and airway remodeling in patients with stable COPD

    Directory of Open Access Journals (Sweden)

    Gui-Fang Hu1

    2017-05-01

    Full Text Available Objective: To study the effect of adjuvant N-acetylcysteine (NAC effervescent tablets therapy on cardiopulmonary function and airway remodeling in patients with stable chronic obstructive pulmonary disease (COPD. Methods: Patients with stable COPD treated in Zigong Third People’s Hospital and West China Hospital, Sichuan University between May 2014 and October 2016 were selected and randomly divided into two groups, NAC group received N-acetylcysteine effervescent tablets combined with routine treatment, and control group received routine treatment. Before treatment as well as 2 weeks and 4 weeks after treatment, oxidative stress indexes and airway remodeling indexes in serum as well as inflammatory response indexes in peripheral blood were determined. Results: MDA, PC, 8-OHdG, MMP2, MMP3 and MMP9 contents in serum as well as NLRP3, ASC, p38MAPK and TREM-1 mRNA expression levels in peripheral blood mononuclear cells of both groups of patients after treatment were significantly lower than those before treatment while TAC levels as well as TIMP1 and TIMP2 contents in serum were significantly higher than those before treatment, and MDA, PC, 8-OHdG, MMP2, MMP3 and MMP9 contents in serum a well as NLRP3, ASC, p38MAPK and TREM-1 mRNA expression levels in peripheral blood mononuclear cells of NAC group after treatment were significantly lower than those of control group while TAC levels as well as TIMP1 and TIMP2 contents in serum were significantly higher than those of control group. Conclusion: Adjuvant NAC effervescent tablets treatment of stable COPD can improve the effect of oxidative stress and inflammatory response on cardiopulmonary function, and inhibit the airway remodeling caused by protease activation.

  4. Fast vessel segmentation in retinal images using multi-scale enhancement and second-order local entropy

    Science.gov (United States)

    Yu, H.; Barriga, S.; Agurto, C.; Zamora, G.; Bauman, W.; Soliz, P.

    2012-03-01

    Retinal vasculature is one of the most important anatomical structures in digital retinal photographs. Accurate segmentation of retinal blood vessels is an essential task in automated analysis of retinopathy. This paper presents a new and effective vessel segmentation algorithm that features computational simplicity and fast implementation. This method uses morphological pre-processing to decrease the disturbance of bright structures and lesions before vessel extraction. Next, a vessel probability map is generated by computing the eigenvalues of the second derivatives of Gaussian filtered image at multiple scales. Then, the second order local entropy thresholding is applied to segment the vessel map. Lastly, a rule-based decision step, which measures the geometric shape difference between vessels and lesions is applied to reduce false positives. The algorithm is evaluated on the low-resolution DRIVE and STARE databases and the publicly available high-resolution image database from Friedrich-Alexander University Erlangen-Nuremberg, Germany). The proposed method achieved comparable performance to state of the art unsupervised vessel segmentation methods with a competitive faster speed on the DRIVE and STARE databases. For the high resolution fundus image database, the proposed algorithm outperforms an existing approach both on performance and speed. The efficiency and robustness make the blood vessel segmentation method described here suitable for broad application in automated analysis of retinal images.

  5. DOPAMINE EFFECT ON CARDIAC REMODELING IN EXPERIMENT

    Directory of Open Access Journals (Sweden)

    V. R. Veber

    2009-01-01

    Full Text Available Aim. To study morphologic changes in myocardium of Wistar rats caused by single and long term dopamine administration.Methods. In acute study dopamine 10 mkg/kg was administrated to 15 rats by a single intraperitoneal injection. The material was taken in 2, 6, 24 hours and in 1 month after drug administration. In chronic study dopamine 10 mkg/kg was administrated to 15 rats 3 times a day by intraperitoneal injections during 2 weeks. The material was taken just after the drug administration was stopped and in 1 month of animals keeping without stress and drug influences. Control group included 15 rats comparable with experimental animals in age and weight. They were keeped without stress and drug influences. Morphometric parameters of left and right ventricles were evaluated as well as density of cardiomyocytes, collagen, vessels and volume of extracellular space.Results. The enlargement of cardiac fibrosis is found both in acute, and in chronic study. In acute study cardiac fibrosis was located mainly in a right ventricle. In chronic study cardiac fibrosis was located in both ventricles, but also mainly in a right one.Conclusion. Significant morphological «asynchronism» of the left and right ventricles remodeling requires elaboration of methods of myocardium protection and cardiac function control during dopamine administration. 

  6. Impact of obesity on hypertension-induced cardiac remodeling: role of oxidative stress and its modulation by gemfibrozil treatment in rats.

    Science.gov (United States)

    Singh, Randhir; Singh, Amrit Pal; Singh, Manjeet; Krishan, Pawan

    2011-01-15

    This study investigated the possible synergistic role of obesity in hypertension-induced cardiac remodeling and its modulation by gemfibrozil treatment in rats. Male Wistar rats were fed a high-fat diet (HFD) for 90 days. Normal rats were subjected to hypertension by partial abdominal aortic constriction (PAAC) for 28 days. In the HFD+PAAC control group, rats on HFD were subjected to PAAC on the 62nd day and were sacrificed on the 90th day. HFD and PAAC individually resulted in significant cardiac hypertrophy and fibrosis along with increased oxidative stress and mean arterial blood pressure (MABP) in rats as evidenced by various morphological, biochemical, and histological parameters. Moreover, the HFD + PAAC control group showed marked cardiac remodeling compared to rats subjected to HFD or PAAC alone. The HFD+gemfibrozil and HFD+PAAC+gemfibrozil groups showed significant reduction in cardiac remodeling along with reduction in oxidative stress and MABP. Hence, it may be concluded that oxidative stress plays a key role in obesity-mediated synergistic effects on induction and progression of PAAC-induced cardiac remodeling, and its deleterious effects could be reversed by gemfibrozil treatment in rats through its antioxidant activity. Copyright © 2010 Elsevier Inc. All rights reserved.

  7. Multimodal imaging of vascular network and blood microcirculation by optical diagnostic techniques

    International Nuclear Information System (INIS)

    Kuznetsov, Yu L; Kalchenko, V V; Meglinski, I V

    2011-01-01

    We present a multimodal optical diagnostic approach for simultaneous non-invasive in vivo imaging of blood and lymphatic microvessels, utilising a combined use of fluorescence intravital microscopy and a method of dynamic light scattering. This approach makes it possible to renounce the use of fluorescent markers for visualisation of blood vessels and, therefore, significantly (tenfold) reduce the toxicity of the technique and minimise side effects caused by the use of contrast fluorescent markers. We demonstrate that along with the ability to obtain images of lymph and blood microvessels with a high spatial resolution, current multimodal approach allows one to observe in real time permeability of blood vessels. This technique appears to be promising in physiology studies of blood vessels, and especially in the study of peripheral cardiovascular system in vivo. (optical technologies in biophysics and medicine)

  8. Title: variations and sensitivities of some blood pressure monitors ...

    African Journals Online (AJOL)

    Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels. Accuracy in blood pressure meters is of essence to health, especially in blood pressure monitoring and treatment. The aim of this research was to compare the readings and the sensitivities of some blood pressure monitors in use ...

  9. Remodeling of ribosomal genes in somatic cells by Xenopus egg extract

    DEFF Research Database (Denmark)

    Østrup, Olga; Hyttel, Poul; Klærke, Dan Arne

    2011-01-01

    Extracts from Xenopus eggs can reprogram gene expression in somatic nuclei, however little is known about the earliest processes associated with the switch in the transcriptional program. We show here that an early reprogramming event is the remodeling of ribosomal chromatin and gene expression....... This occurs within hours of extract treatment and is distinct from a stress response. Egg extract elicits remodeling of the nuclear envelope, chromatin and nucleolus. Nucleolar remodeling involves a rapid and stable decrease in ribosomal gene transcription, and promoter targeting of the nucleolar remodeling...... and elicits a stress-type nuclear response. Thus, an early event of Xenopus egg extract-mediated nuclear reprogramming is the remodeling of ribosomal genes involving nucleolar remodeling complex. Condition-specific and rapid silencing of ribosomal genes may serve as a sensitive marker for evaluation...

  10. Galectin-3 and post-myocardial infarction cardiac remodeling

    NARCIS (Netherlands)

    Meijers, Wouter C.; van der Velde, A. Rogier; Pascual-Figal, Domingo A.; de Boer, Rudolf A.

    2015-01-01

    This review summarizes the current literature regarding the involvement and the putative role(s) of galectin-3 in post-myocardial infarction cardiac remodeling. Post-myocardial infarction remodeling is characterized by acute loss of myocardium, which leads to structural and biomechanical changes in

  11. The behavior of adaptive bone-remodeling simulation models

    NARCIS (Netherlands)

    H.H. Weinans (Harrie); R. Huiskes (Rik); H.J. Grootenboer

    1992-01-01

    textabstractThe process of adaptive bone remodeling can be described mathematically and simulated in a computer model, integrated with the finite element method. In the model discussed here, cortical and trabecular bone are described as continuous materials with variable density. The remodeling rule

  12. Supervised retinal vessel segmentation from color fundus images based on matched filtering and AdaBoost classifier.

    Directory of Open Access Journals (Sweden)

    Nogol Memari

    Full Text Available The structure and appearance of the blood vessel network in retinal fundus images is an essential part of diagnosing various problems associated with the eyes, such as diabetes and hypertension. In this paper, an automatic retinal vessel segmentation method utilizing matched filter techniques coupled with an AdaBoost classifier is proposed. The fundus image is enhanced using morphological operations, the contrast is increased using contrast limited adaptive histogram equalization (CLAHE method and the inhomogeneity is corrected using Retinex approach. Then, the blood vessels are enhanced using a combination of B-COSFIRE and Frangi matched filters. From this preprocessed image, different statistical features are computed on a pixel-wise basis and used in an AdaBoost classifier to extract the blood vessel network inside the image. Finally, the segmented images are postprocessed to remove the misclassified pixels and regions. The proposed method was validated using publicly accessible Digital Retinal Images for Vessel Extraction (DRIVE, Structured Analysis of the Retina (STARE and Child Heart and Health Study in England (CHASE_DB1 datasets commonly used for determining the accuracy of retinal vessel segmentation methods. The accuracy of the proposed segmentation method was comparable to other state of the art methods while being very close to the manual segmentation provided by the second human observer with an average accuracy of 0.972, 0.951 and 0.948 in DRIVE, STARE and CHASE_DB1 datasets, respectively.

  13. Pulmonary Remodeling in Equine Asthma: What Do We Know about Mediators of Inflammation in the Horse?

    Science.gov (United States)

    Gehlen, Heidrun

    2016-01-01

    Equine inflammatory airway disease (IAD) and recurrent airway obstruction (RAO) represent a spectrum of chronic inflammatory disease of the airways in horses resembling human asthma in many aspects. Therefore, both are now described as severity grades of equine asthma. Increasing evidence in horses and humans suggests that local pulmonary inflammation is influenced by systemic inflammatory processes and the other way around. Inflammation, coagulation, and fibrinolysis as well as extracellular remodeling show close interactions. Cytology of bronchoalveolar lavage fluid and tracheal wash is commonly used to evaluate the severity of local inflammation in the lung. Other mediators of inflammation, like interleukins involved in the chemotaxis of neutrophils, have been studied. Chronic obstructive pneumopathies lead to remodeling of bronchial walls and lung parenchyma, ultimately causing fibrosis. Matrix metalloproteinases (MMPs) are discussed as the most important proteolytic enzymes during remodeling in human medicine and increasing evidence exists for the horse as well. A systemic involvement has been shown for severe equine asthma by increased acute phase proteins like serum amyloid A and haptoglobin in peripheral blood during exacerbation. Studies focusing on these and further possible inflammatory markers for chronic respiratory disease in the horse are discussed in this review of the literature. PMID:28053371

  14. Visual function and retinal vessel diameters during hyperthermia in man

    DEFF Research Database (Denmark)

    Jensen, Bettina Hagström; Bram, Thue; Kappelgaard, Per

    2017-01-01

    .01), a 10.6-mmHg mean reduction in diastolic blood pressure (p vein...... laser ophthalmoscopy was used to measure retinal trunk vessel diameters. Assessment was made at baseline, during hyperthermia and after cooling. RESULTS: The induction of a mean increase in core body temperature of 1.02°C was associated with a 7.15-mmHg mean reduction in systolic blood pressure (p

  15. Laser speckle contrast imaging of skin blood perfusion responses induced by laser coagulation

    Energy Technology Data Exchange (ETDEWEB)

    Ogami, M; Kulkarni, R; Wang, H; Reif, R; Wang, R K [University of Washington, Department of Bioengineering, Seattle, Washington 98195 (United States)

    2014-08-31

    We report application of laser speckle contrast imaging (LSCI), i.e., a fast imaging technique utilising backscattered light to distinguish such moving objects as red blood cells from such stationary objects as surrounding tissue, to localise skin injury. This imaging technique provides detailed information about the acute perfusion response after a blood vessel is occluded. In this study, a mouse ear model is used and pulsed laser coagulation serves as the method of occlusion. We have found that the downstream blood vessels lacked blood flow due to occlusion at the target site immediately after injury. Relative flow changes in nearby collaterals and anastomotic vessels have been approximated based on differences in intensity in the nearby collaterals and anastomoses. We have also estimated the density of the affected downstream vessels. Laser speckle contrast imaging is shown to be used for highresolution and fast-speed imaging for the skin microvasculature. It also allows direct visualisation of the blood perfusion response to injury, which may provide novel insights to the field of cutaneous wound healing. (laser biophotonics)

  16. Laser speckle contrast imaging of skin blood perfusion responses induced by laser coagulation

    Science.gov (United States)

    Ogami, M.; Kulkarni, R.; Wang, H.; Reif, R.; Wang, R. K.

    2014-08-01

    We report application of laser speckle contrast imaging (LSCI), i.e., a fast imaging technique utilising backscattered light to distinguish such moving objects as red blood cells from such stationary objects as surrounding tissue, to localise skin injury. This imaging technique provides detailed information about the acute perfusion response after a blood vessel is occluded. In this study, a mouse ear model is used and pulsed laser coagulation serves as the method of occlusion. We have found that the downstream blood vessels lacked blood flow due to occlusion at the target site immediately after injury. Relative flow changes in nearby collaterals and anastomotic vessels have been approximated based on differences in intensity in the nearby collaterals and anastomoses. We have also estimated the density of the affected downstream vessels. Laser speckle contrast imaging is shown to be used for highresolution and fast-speed imaging for the skin microvasculature. It also allows direct visualisation of the blood perfusion response to injury, which may provide novel insights to the field of cutaneous wound healing.

  17. Left ventricular remodeling in preclinical experimental mitral regurgitation of dogs.

    Science.gov (United States)

    Dillon, A Ray; Dell'Italia, Louis J; Tillson, Michael; Killingsworth, Cheryl; Denney, Thomas; Hathcock, John; Botzman, Logan

    2012-03-01

    Dogs with experimental mitral regurgitation (MR) provide insights into the left ventricular remodeling in preclinical MR. The early preclinical left ventricular (LV) changes after mitral regurgitation represent progressive dysfunctional remodeling, in that no compensatory response returns the functional stroke volume (SV) to normal even as total SV increases. The gradual disease progression leads to mitral annulus stretch and enlargement of the regurgitant orifice, further increasing the regurgitant volume. Remodeling with loss of collagen weave and extracellular matrix (ECM) is accompanied by stretching and hypertrophy of the cross-sectional area and length of the cardiomyocyte. Isolated ventricular cardiomyocytes demonstrate dysfunction based on decreased cell shortening and reduced intracellular calcium transients before chamber enlargement or decreases in contractility in the whole heart can be clinically appreciated. The genetic response to increased end-diastolic pressure is down-regulation of genes associated with support of the collagen and ECM and up-regulation of genes associated with matrix remodeling. Experiments have not demonstrated any beneficial effects on remodeling from treatments that decrease afterload via blocking the renin-angiotensin system (RAS). Beta-1 receptor blockade and chymase inhibition have altered the progression of the LV remodeling and have supported cardiomyocyte function. The geometry of the LV during the remodeling provides insight into the importance of regional differences in responses to wall stress. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Transplantation of Normal Adipose Tissue Improves Blood Flow and Reduces Inflammation in High Fat Fed Mice With Hindlimb Ischemia

    Directory of Open Access Journals (Sweden)

    Liyuan Chen

    2018-03-01

    Full Text Available Background: Fat deposition is associated with peripheral arterial disease. Adipose tissue has recently been implicated in vascular remodeling and angiogenic activity. We hypothesized that the transplantation of adipose tissues from normal mice improves blood flow perfusion and neovascularization in high-fat diet fed mice.Methods: After 14 weeks of high-fat diet (HFD-fed mice, unilateral hind limb ischemia was performed. Subcutaneous white adipose tissue (WAT and brown adipose tissue (BAT fat pads were harvested from normal EGFP mice, and subcutaneously transplanted over the region of the adductor muscles of HFD mice. Blood flow was measured using Laser Doppler Scanner. Vascular density, macrophages infiltration, and macrophage polarization were examined by RT-qPCR, and immunohistochemistry.Results: We found that the transplantation of WAT derived from normal mice improved functional blood flow in HFD-fed mice compared to mice transplanted with BAT and sham-treated mice. WAT transplantation increased the recruitment of pericytes associated with nascent blood vessels, but did not affect capillary formation. Furthermore, transplantation of WAT ameliorated HFD-induced insulin resistance, M2 macrophage predominance and the release of arteriogenic factors in ischemic muscles. Mice receiving WAT also displayed a marked reduction in several proinflammatory cytokines. In contrast, mice transplanted with BAT were glucose intolerant and demonstrated increased IL-6 levels in ischemic muscles.Conclusion: These results indicate that transplantation of adipose tissue elicits improvements in blood perfusion and beneficial effects on systemic glucose homeostasis and could be a promising therapeutic option for the treatment of diabetic peripheral arterial disease.

  19. Circulating NOS3 modulates left ventricular remodeling following reperfused myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Simone Gorressen

    Full Text Available Nitric oxide (NO is constitutively produced and released from the endothelium and several blood cell types by the isoform 3 of the NO synthase (NOS3. We have shown that NO protects against myocardial ischemia/reperfusion (I/R injury and that depletion of circulating NOS3 increases within 24 h of ischemia/reperfusion the size of myocardial infarction (MI in chimeric mice devoid of circulating NOS3. In the current study we hypothesized that circulating NOS3 also affects remodeling of the left ventricle following reperfused MI.To analyze the role of circulating NOS3 we transplanted bone marrow of NOS3-/- and wild type (WT mice into WT mice, producing chimerae expressing NOS3 only in vascular endothelium (BC-/EC+ or in both, blood cells and vascular endothelium (BC+/EC+. Both groups underwent 60 min of coronary occlusion in a closed-chest model of reperfused MI. During the 3 weeks post MI, structural and functional LV remodeling was serially assessed (24 h, 4 d, 1 w, 2 w and 3 w by echocardiography. At 72 hours post MI, gene expression of several extracellular matrix (ECM modifying molecules was determined by quantitative RT-PCR analysis. At 3 weeks post MI, hemodynamics were obtained by pressure catheter, scar size and collagen content were quantified post mortem by Gomori's One-step trichrome staining.Three weeks post MI, LV end-systolic (53.2±5.9 μl; ***p≤0.001; n = 5 and end-diastolic volumes (82.7±5.6 μl; *p<0.05; n = 5 were significantly increased in BC-/EC+, along with decreased LV developed pressure (67.5±1.8 mm Hg; n = 18; ***p≤0.001 and increased scar size/left ventricle (19.5±1.5%; n = 13; **p≤0.01 compared to BC+/EC+ (ESV: 35.6±2.2 μl; EDV: 69.1±2.6 μl n = 8; LVDP: 83.2±3.2 mm Hg; n = 24; scar size/LV13.8±0.7%; n = 16. Myocardial scar of BC-/EC+ was characterized by increased total collagen content (20.2±0.8%; n = 13; ***p≤0.001 compared to BC+/EC+ (15.9±0.5; n = 16, and increased collagen type I and III subtypes

  20. Effects of the tumor-vasculature-disrupting agent verubulin and two heteroaryl analogues on cancer cells, endothelial cells, and blood vessels.

    Science.gov (United States)

    Mahal, Katharina; Resch, Marcus; Ficner, Ralf; Schobert, Rainer; Biersack, Bernhard; Mueller, Thomas

    2014-04-01

    Two analogues of the discontinued tumor vascular-disrupting agent verubulin (Azixa®, MPC-6827, 1) featuring benzo-1,4-dioxan-6-yl (compound 5 a) and N-methylindol-5-yl (compound 10) residues instead of the para-anisyl group on the 4-(methylamino)-2-methylquinazoline pharmacophore, were prepared and found to exceed the antitumor efficacy of the lead compound. They were antiproliferative with single-digit nanomolar IC50 values against a panel of nine tumor cell lines, while not affecting nonmalignant fibroblasts. Indole 10 surpassed verubulin in seven tumor cell lines including colon, breast, ovarian, and germ cell cancer cell lines. In line with docking studies indicating that compound 10 may bind the colchicine binding site of tubulin more tightly (Ebind =-9.8 kcal mol(-1) ) than verubulin (Ebind =-8.3 kcal mol(-1) ), 10 suppressed the formation of vessel-like tubes in endothelial cells and destroyed the blood vessels in the chorioallantoic membrane of fertilized chicken eggs at nanomolar concentrations. When applied to nude mice bearing a highly vascularized 1411HP germ cell xenograft tumor, compound 10 displayed pronounced vascular-disrupting effects that led to hemorrhages and extensive central necrosis in the tumor. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.