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Sample records for abnormal vascular network

  1. Development of Abnormal Hemispheric Vascular Networks Mimicking Cerebral Proliferative Angiopathy in a Child Originally Diagnosed with Deep-Seated Arteriovenous Fistula.

    PubMed

    Sakata, Hiroyuki; Fujimura, Miki; Sato, Kenichi; Niizuma, Kuniyasu; Endo, Hidenori; Tominaga, Teiji

    2016-10-01

    Cerebral proliferative angiopathy (CPA), which is characterized by diffuse vascular abnormalities with intermingled normal brain parenchyma, is a rare clinical entity distinct from classical cerebral arteriovenous malformations. Its pathology at initial state and subsequent course of progression has totally been undetermined. We herein presented a case of a child who was initially diagnosed with deep-seated arteriovenous fistula (AVF), and ultimately developed symptomatic CPA-like vascular lesion over a long period of clinical follow-up. A 7-month-old boy was incidentally found to have an AVF in the right basal ganglia and conservatively followed up. Serial magnetic resonance angiograms revealed the gradual proliferation and enlargement of pial and medullary vessels surrounding the AVF. Seven years later, he had a transient ischemic attack followed by intraventricular hemorrhage. A catheter angiogram showed a diffuse large vascular malformation composed of 2 distinct structures, including AVF in the right basal ganglia and the surrounding proliferated pial and medullary arteries in the right hemisphere. Single-photon emission computed tomography with N-isopropyl[123I]-p-iodoamphetamine revealed apparent hemodynamic compromise on the right hemisphere. Targeted embolization of the pseudoaneurysm originating from the right A1 perforator was performed to prevent rebleeding without complications. The patient had no further cerebrovascular events. Perinidal hypoperfusion induced by a deep-seated AVF could be one of the underlying pathologies of progressive angiogenic activity. This is the first case showing the development of abnormal hemispheric vascular networks mimicking CPA, which offers insight into the pathogenesis of this new entity.

  2. Building Vascular Networks

    PubMed Central

    Bae, Hojae; Puranik, Amey S.; Gauvin, Robert; Edalat, Faramarz; Carrillo-Conde, Brenda; Peppas, Nicholas A.; Khademhosseini, Ali

    2013-01-01

    Only a few engineered tissues—skin, cartilage, bladder—have achieved clinical success, and biomaterials designed to replace more complex organs are still far from commercial availability. This gap exists in part because biomaterials lack a vascular network to transfer the oxygen and nutrients necessary for survival and integration after transplantation. Thus, generation of a functional vasculature is essential to the clinical success of engineered tissue constructs and remains a key challenge for regenerative medicine. In this Perspective, we discuss recent advances in vascularization of biomaterials through the use of biochemical modification, exogenous cells, or microengineering technology. PMID:23152325

  3. Retina vascular network recognition

    NASA Astrophysics Data System (ADS)

    Tascini, Guido; Passerini, Giorgio; Puliti, Paolo; Zingaretti, Primo

    1993-09-01

    The analysis of morphological and structural modifications of the retina vascular network is an interesting investigation method in the study of diabetes and hypertension. Normally this analysis is carried out by qualitative evaluations, according to standardized criteria, though medical research attaches great importance to quantitative analysis of vessel color, shape and dimensions. The paper describes a system which automatically segments and recognizes the ocular fundus circulation and micro circulation network, and extracts a set of features related to morphometric aspects of vessels. For this class of images the classical segmentation methods seem weak. We propose a computer vision system in which segmentation and recognition phases are strictly connected. The system is hierarchically organized in four modules. Firstly the Image Enhancement Module (IEM) operates a set of custom image enhancements to remove blur and to prepare data for subsequent segmentation and recognition processes. Secondly the Papilla Border Analysis Module (PBAM) automatically recognizes number, position and local diameter of blood vessels departing from optical papilla. Then the Vessel Tracking Module (VTM) analyses vessels comparing the results of body and edge tracking and detects branches and crossings. Finally the Feature Extraction Module evaluates PBAM and VTM output data and extracts some numerical indexes. Used algorithms appear to be robust and have been successfully tested on various ocular fundus images.

  4. Pulmonary vascular development goes awry in congenital lung abnormalities.

    PubMed

    Kool, Heleen; Mous, Daphne; Tibboel, Dick; de Klein, Annelies; Rottier, Robbert J

    2014-12-01

    Pulmonary vascular diseases of the newborn comprise a wide range of pathological conditions with developmental abnormalities in the pulmonary vasculature. Clinically, pulmonary arterial hypertension (PH) is characterized by persistent increased resistance of the vasculature and abnormal vascular response. The classification of PH is primarily based on clinical parameters instead of morphology and distinguishes five groups of PH. Congenital lung anomalies, such as alveolar capillary dysplasia (ACD) and PH associated with congenital diaphragmatic hernia (CDH), but also bronchopulmonary dysplasia (BPD), are classified in group three. Clearly, tight and correct regulation of pulmonary vascular development is crucial for normal lung development. Human and animal model systems have increased our knowledge and make it possible to identify and characterize affected pathways and study pivotal genes. Understanding of the normal development of the pulmonary vasculature will give new insights in the origin of the spectrum of rare diseases, such as CDH, ACD, and BPD, which render a significant clinical problem in neonatal intensive care units around the world. In this review, we describe normal pulmonary vascular development, and focus on four diseases of the newborn in which abnormal pulmonary vascular development play a critical role in morbidity and mortality. In the future perspective, we indicate the lines of research that seem to be very promising for elucidating the molecular pathways involved in the origin of congenital pulmonary vascular disease. PMID:25424472

  5. Pulmonary Hypertension and Vascular Abnormalities in Bronchopulmonary Dysplasia.

    PubMed

    Mourani, Peter M; Abman, Steven H

    2015-12-01

    Despite advances in the care of preterm infants, these infants remain at risk bronchopulmonary dysplasia (BPD), which results in prolonged need for supplemental oxygen, recurrent respiratory exacerbations, and exercise intolerance. Recent investigations have highlighted the important contribution of the developing pulmonary circulation to lung development, showing that these infants are also at risk for pulmonary vascular disease (PVD), including pulmonary hypertension (PH) and pulmonary vascular abnormalities. Several epidemiologic studies have delineated the incidence of PH in preterm infants and the impact on outcomes. These studies have also highlighted gaps in the understanding of PVD in BPD. PMID:26593082

  6. Abnormalities of vascular structure and function in pediatric hypertension.

    PubMed

    Urbina, Elaine M

    2016-07-01

    Hypertension is associated with adverse cardiovascular (CV) events in adults. Measures of vascular structure and function, including increased carotid intima-media thickness (cIMT) and elevated arterial stiffness predict hard CV events in adulthood. Newer data suggest that abnormalities in target organ damage are occurring in adolescents and young adults with high blood pressure. In this review, we discuss the techniques for measuring vascular dysfunction in young people and the evidence linking blood pressure levels to this type of target organ damage.

  7. Schizophrenia and abnormal brain network hubs

    PubMed Central

    Rubinov, Mikail; Bullmore, Ed.

    2013-01-01

    Schizophrenia is a heterogeneous psychiatric disorder of unknown cause or characteristic pathology. Clinical neuroscientists increasingly postulate that schizophrenia is a disorder of brain network organization. In this article we discuss the conceptual framework of this dysconnection hypothesis, describe the predominant methodological paradigm for testing this hypothesis, and review recent evidence for disruption of central/hub brain regions, as a promising example of this hypothesis. We summarize studies of brain hubs in large-scale structural and functional brain networks and find strong evidence for network abnormalities of prefrontal hubs, and moderate evidence for network abnormalities of limbic, temporal, and parietal hubs. Future studies are needed to differentiate network dysfunction from previously observed gray- and white-matter abnormalities of these hubs, and to link endogenous network dysfunction phenotypes with perceptual, behavioral, and cognitive clinical phenotypes of schizophrenia. PMID:24174905

  8. Schizophrenia and abnormal brain network hubs.

    PubMed

    Rubinov, Mikail; Bullmore, Ed

    2013-09-01

    Schizophrenia is a heterogeneous psychiatric disorder of unknown cause or characteristic pathology. Clinical neuroscientists increasingly postulate that schizophrenia is a disorder of brain network organization. In this article we discuss the conceptual framework of this dysconnection hypothesis, describe the predominant methodological paradigm for testing this hypothesis, and review recent evidence for disruption of central/hub brain regions, as a promising example of this hypothesis. We summarize studies of brain hubs in large-scale structural and functional brain networks and find strong evidence for network abnormalities of prefrontal hubs, and moderate evidence for network abnormalities of limbic, temporal, and parietal hubs. Future studies are needed to differentiate network dysfunction from previously observed gray- and white-matter abnormalities of these hubs, and to link endogenous network dysfunction phenotypes with perceptual, behavioral, and cognitive clinical phenotypes of schizophrenia.

  9. High Interstitial Fluid Pressure Is Associated with Tumor-Line Specific Vascular Abnormalities in Human Melanoma Xenografts

    PubMed Central

    Simonsen, Trude G.; Gaustad, Jon-Vidar; Leinaas, Marit N.; Rofstad, Einar K.

    2012-01-01

    Purpose Interstitial fluid pressure (IFP) is highly elevated in many solid tumors. High IFP has been associated with low radiocurability and high metastatic frequency in human melanoma xenografts and with poor survival after radiation therapy in cervical cancer patients. Abnormalities in tumor vascular networks have been identified as an important cause of elevated tumor IFP. The aim of this study was to investigate the relationship between tumor IFP and the functional and morphological properties of tumor vascular networks. Materials and Methods A-07-GFP and R-18-GFP human melanomas growing in dorsal window chambers in BALB/c nu/nu mice were used as preclinical tumor models. Functional and morphological parameters of the vascular network were assessed from first-pass imaging movies and vascular maps recorded after intravenous bolus injection of 155-kDa tetramethylrhodamine isothiocyanate-labeled dextran. IFP was measured in the center of the tumors using a Millar catheter. Angiogenic profiles of A-07-GFP and R-18-GFP cells were obtained with a quantitative PCR array. Results High IFP was associated with low growth rate and low vascular density in A-07-GFP tumors, and with high growth rate and high vascular density in R-18-GFP tumors. A-07-GFP tumors showed chaotic and highly disorganized vascular networks, while R-18-GFP tumors showed more organized vascular networks with supplying arterioles in the tumor center and draining venules in the tumor periphery. Furthermore, A-07-GFP and R-18-GFP cells differed substantially in angiogenic profiles. A-07-GFP tumors with high IFP showed high geometric resistance to blood flow due to high vessel tortuosity. R-18-GFP tumors with high IFP showed high geometric resistance to blood flow due to a large number of narrow tumor capillaries. Conclusions High IFP in A-07-GFP and R-18-GFP human melanoma xenografts was primarily a consequence of high blood flow resistance caused by tumor-line specific vascular abnormalities. PMID

  10. Plasma concentrations of endothelin in patients with abnormal vascular reactivity

    SciTech Connect

    Predel, H.G.; Meyer-Lehnert, H.; Baecker, A.; Stelkens, H.; Kramer, H.J. )

    1990-01-01

    We measured circulating concentrations of endothelin in healthy subjects and in patients with abnormal vascular reactivity. Endothelin concentrations were determined by radioimmunoassay after extraction of plasma using Sep-Pak C-18 cartridges in healthy subjects, in patients with diabetes mellitus type I, in patients with mild to moderate essential hypertension and in non-dialyzed patients with stable chronic renal failure. Plasma concentrations were similar in healthy controls, in diabetics and in hypertensive patients averaging 5.0{plus minus}0.6 pg/ml, 4.7{plus minus}0.2 pg/ml and 6.5{plus minus}1.0 pg/ml, respectively. In contrast, plasma concentrations of endothelin were markedly elevated in patients with chronic renal failure averaging 16.6{plus minus}2.9 pg/ml. No correlations were observed between serum creatinine concentrations ranging from 124 to 850 {mu}mol/l or blood pressure and plasma concentrations of endothelin. Bicycle ergometric exercise in six healthy subjects and an acute modest i.v. saline load of 1,000 ml of 0.45% NaCl administered within 60 min in six patients with mild essential hypertension did not affect plasma concentrations of endothelin.

  11. Geometry optimization of branchings in vascular networks

    NASA Astrophysics Data System (ADS)

    Khamassi, Jamel; Bierwisch, Claas; Pelz, Peter

    2016-06-01

    Progress has been made in developing manufacturing technologies which enable the fabrication of artificial vascular networks for tissue cultivation. However, those networks are rudimentary designed with respect to their geometry. This restricts long-term biological functionality of vascular cells which depends on geometry-related fluid mechanical stimuli and the avoidance of vessel occlusion. In the present work, a bioinspired geometry optimization for branchings in artificial vascular networks has been conducted. The analysis could be simplified by exploiting self-similarity properties of the system. Design rules in the form of two geometrical parameters, i.e., the branching angle and the radius ratio of the daughter branches, are derived using the wall shear stress as command variable. The numerical values of these parameters are within the range of experimental observations. Those design rules are not only beneficial for tissue engineering applications. Moreover, they can be used as indicators for diagnoses of vascular diseases or for the layout of vascular grafts.

  12. Tissue engineering: Perfusable vascular networks

    NASA Astrophysics Data System (ADS)

    Forgacs, Gabor

    2012-09-01

    A rapid vascular casting approach that uses carbohydrate glass as a sacrificial template allows tissues to be built that can be kept alive for longer in the laboratory until needed for transplantation.

  13. Hydrogels for Engineering of Perfusable Vascular Networks

    PubMed Central

    Liu, Juan; Zheng, Huaiyuan; Poh, Patrina S. P.; Machens, Hans-Günther; Schilling, Arndt F.

    2015-01-01

    Hydrogels are commonly used biomaterials for tissue engineering. With their high-water content, good biocompatibility and biodegradability they resemble the natural extracellular environment and have been widely used as scaffolds for 3D cell culture and studies of cell biology. The possible size of such hydrogel constructs with embedded cells is limited by the cellular demand for oxygen and nutrients. For the fabrication of large and complex tissue constructs, vascular structures become necessary within the hydrogels to supply the encapsulated cells. In this review, we discuss the types of hydrogels that are currently used for the fabrication of constructs with embedded vascular networks, the key properties of hydrogels needed for this purpose and current techniques to engineer perfusable vascular structures into these hydrogels. We then discuss directions for future research aimed at engineering of vascularized tissue for implantation. PMID:26184185

  14. Hydrogels for Engineering of Perfusable Vascular Networks.

    PubMed

    Liu, Juan; Zheng, Huaiyuan; Poh, Patrina S P; Machens, Hans-Günther; Schilling, Arndt F

    2015-07-14

    Hydrogels are commonly used biomaterials for tissue engineering. With their high-water content, good biocompatibility and biodegradability they resemble the natural extracellular environment and have been widely used as scaffolds for 3D cell culture and studies of cell biology. The possible size of such hydrogel constructs with embedded cells is limited by the cellular demand for oxygen and nutrients. For the fabrication of large and complex tissue constructs, vascular structures become necessary within the hydrogels to supply the encapsulated cells. In this review, we discuss the types of hydrogels that are currently used for the fabrication of constructs with embedded vascular networks, the key properties of hydrogels needed for this purpose and current techniques to engineer perfusable vascular structures into these hydrogels. We then discuss directions for future research aimed at engineering of vascularized tissue for implantation.

  15. Dynamics of nephron-vascular network.

    PubMed

    Postnov, D D; Postnov, D E; Marsh, D J; Holstein-Rathlou, N-H; Sosnovtseva, O V

    2012-12-01

    The paper presents a modeling study of the spatial dynamics of a nephro-vascular network consisting of individual nephrons connected via a tree-like vascular branching structure. We focus on the effects of nonlinear mechanisms that are responsible for the formation of synchronous patterns in order to learn about processes not directly amenable to experimentation. We demonstrate that: (i) the nearest nephrons are synchronized in-phase due to a vascular propagated electrical coupling, (ii) the next few branching levels display a formation of phase-shifted patterns due to hemodynamic coupling and mode elimination, and (iii) distantly located areas show asynchronous behavior or, if all nephrons and branches are perfectly identical, an infinitely long transient behavior. These results contribute to the understanding of mechanisms responsible for the highly dynamic and limited synchronization observed among groups of nephrons despite of the fairly strong interaction between the individual units.

  16. Abnormal Vascular Function and Hypertension in Mice Deficient in Estrogen Receptor β

    NASA Astrophysics Data System (ADS)

    Zhu, Yan; Bian, Zhao; Lu, Ping; Karas, Richard H.; Bao, Lin; Cox, Daniel; Hodgin, Jeffrey; Shaul, Philip W.; Thorén, Peter; Smithies, Oliver; Gustafsson, Jan-Åke; Mendelsohn, Michael E.

    2002-01-01

    Blood vessels express estrogen receptors, but their role in cardiovascular physiology is not well understood. We show that vascular smooth muscle cells and blood vessels from estrogen receptor β (ERβ)-deficient mice exhibit multiple functional abnormalities. In wild-type mouse blood vessels, estrogen attenuates vasoconstriction by an ERβ-mediated increase in inducible nitric oxide synthase expression. In contrast, estrogen augments vasoconstriction in blood vessels from ERβ-deficient mice. Vascular smooth muscle cells isolated from ERβ-deficient mice show multiple abnormalities of ion channel function. Furthermore, ERβ-deficient mice develop sustained systolic and diastolic hypertension as they age. These data support an essential role for ERβ in the regulation of vascular function and blood pressure.

  17. Pleiotrophin promotes vascular abnormalization in gliomas and correlates with poor survival in patients with astrocytomas.

    PubMed

    Zhang, Lei; Kundu, Soumi; Feenstra, Tjerk; Li, Xiujuan; Jin, Chuan; Laaniste, Liisi; El Hassan, Tamador Elsir Abu; Ohlin, K Elisabet; Yu, Di; Olofsson, Tommie; Olsson, Anna-Karin; Pontén, Fredrik; Magnusson, Peetra U; Nilsson, Karin Forsberg; Essand, Magnus; Smits, Anja; Dieterich, Lothar C; Dimberg, Anna

    2015-12-01

    Glioblastomas are aggressive astrocytomas characterized by endothelial cell proliferation and abnormal vasculature, which can cause brain edema and increase patient morbidity. We identified the heparin-binding cytokine pleiotrophin as a driver of vascular abnormalization in glioma. Pleiotrophin abundance was greater in high-grade human astrocytomas and correlated with poor survival. Anaplastic lymphoma kinase (ALK), which is a receptor that is activated by pleiotrophin, was present in mural cells associated with abnormal vessels. Orthotopically implanted gliomas formed from GL261 cells that were engineered to produce pleiotrophin showed increased microvessel density and enhanced tumor growth compared with gliomas formed from control GL261 cells. The survival of mice with pleiotrophin-producing gliomas was shorter than that of mice with gliomas that did not produce pleiotrophin. Vessels in pleiotrophin-producing gliomas were poorly perfused and abnormal, a phenotype that was associated with increased deposition of vascular endothelial growth factor (VEGF) in direct proximity to the vasculature. The growth of pleiotrophin-producing GL261 gliomas was inhibited by treatment with the ALK inhibitor crizotinib, the ALK inhibitor ceritinib, or the VEGF receptor inhibitor cediranib, whereas control GL261 tumors did not respond to either inhibitor. Our findings link pleiotrophin abundance in gliomas with survival in humans and mice, and show that pleiotrophin promotes glioma progression through increased VEGF deposition and vascular abnormalization. PMID:26645582

  18. Vascularization and Angiogenesis in Tissue Engineering: Beyond Creating Static Networks.

    PubMed

    Rouwkema, Jeroen; Khademhosseini, Ali

    2016-09-01

    Engineered tissues need a vascular network to supply cells with nutrients and oxygen after implantation. A network that can connect to the vasculature of the patient after implantation can be included during in vitro culture. For optimal integration, this network needs to be highly organized, including venules, capillaries, and arterioles, to supply all of the cells with sufficient nutrients. Owing to the importance of vascularization for the clinical applicability of tissue engineering, many approaches have been investigated to include an organized vascular network in tissue constructs. This review will give an overview of recent efforts, and will propose future perspectives to engineer the optimal, functional vascular network. PMID:27032730

  19. Comprehensive automatic assessment of retinal vascular abnormalities for computer-assisted retinopathy grading.

    PubMed

    Joshi, Vinayak; Agurto, Carla; VanNess, Richard; Nemeth, Sheila; Soliz, Peter; Barriga, Simon

    2014-01-01

    One of the most important signs of systemic disease that presents on the retina is vascular abnormalities such as in hypertensive retinopathy. Manual analysis of fundus images by human readers is qualitative and lacks in accuracy, consistency and repeatability. Present semi-automatic methods for vascular evaluation are reported to increase accuracy and reduce reader variability, but require extensive reader interaction; thus limiting the software-aided efficiency. Automation thus holds a twofold promise. First, decrease variability while increasing accuracy, and second, increasing the efficiency. In this paper we propose fully automated software as a second reader system for comprehensive assessment of retinal vasculature; which aids the readers in the quantitative characterization of vessel abnormalities in fundus images. This system provides the reader with objective measures of vascular morphology such as tortuosity, branching angles, as well as highlights of areas with abnormalities such as artery-venous nicking, copper and silver wiring, and retinal emboli; in order for the reader to make a final screening decision. To test the efficacy of our system, we evaluated the change in performance of a newly certified retinal reader when grading a set of 40 color fundus images with and without the assistance of the software. The results demonstrated an improvement in reader's performance with the software assistance, in terms of accuracy of detection of vessel abnormalities, determination of retinopathy, and reading time. This system enables the reader in making computer-assisted vasculature assessment with high accuracy and consistency, at a reduced reading time.

  20. Influence of network topology on the abnormal phase order

    NASA Astrophysics Data System (ADS)

    Zhou, Yinzuo; Zhou, Jie; Liu, Zonghua

    2008-12-01

    The abnormal phase order of coupled logistic maps, i.e., the ratio of two sequential "up phases" in the total iterations, can be characterized by the direction phase (Phys. Rev. Lett., 84 (2000) 2610). We here consider the case of coupled logistic maps on complex networks and study how the network topology influences the abnormal phase order. Our numerical simulations reveal that the critical point for the appearance of abnormal phase order increases with the coupling strength but decreases with the degree of heterogeneity of complex networks. Moreover, we find that unlike in the case of normal phase order, it is possible for the system to show a periodic window in the case of abnormal phase order, but only within an appropriate range of coupling strengths, and finally, that the heterogeneity can reduce the maximum number of the phase clusters in a given periodic window.

  1. Quantitative optical coherence tomography angiography of vascular abnormalities in the living human eye

    PubMed Central

    Jia, Yali; Bailey, Steven T.; Hwang, Thomas S.; McClintic, Scott M.; Pennesi, Mark E.; Flaxel, Christina J.; Lauer, Andreas K.; Wilson, David J.; Hornegger, Joachim; Fujimoto, James G.; Huang, David

    2015-01-01

    Retinal vascular diseases are important causes of vision loss. A detailed evaluation of the vascular abnormalities facilitates diagnosis and treatment in these diseases. Optical coherence tomography (OCT) angiography using the highly efficient split-spectrum amplitude decorrelation angiography algorithm offers an alternative to conventional dye-based retinal angiography. OCT angiography has several advantages, including 3D visualization of retinal and choroidal circulations (including the choriocapillaris) and avoidance of dye injection-related complications. Results from six illustrative cases are reported. In diabetic retinopathy, OCT angiography can detect neovascularization and quantify ischemia. In age-related macular degeneration, choroidal neovascularization can be observed without the obscuration of details caused by dye leakage in conventional angiography. Choriocapillaris dysfunction can be detected in the nonneovascular form of the disease, furthering our understanding of pathogenesis. In choroideremia, OCT's ability to show choroidal and retinal vascular dysfunction separately may be valuable in predicting progression and assessing treatment response. OCT angiography shows promise as a noninvasive alternative to dye-based angiography for highly detailed, in vivo, 3D, quantitative evaluation of retinal vascular abnormalities. PMID:25897021

  2. Primary hypertension is a disease of premature vascular aging associated with neuro-immuno-metabolic abnormalities.

    PubMed

    Litwin, Mieczysław; Feber, Janusz; Niemirska, Anna; Michałkiewicz, Jacek

    2016-02-01

    There is an increasing amount of data indicating that primary hypertension (PH) is not only a hemodynamic phenomenon but also a complex syndrome involving abnormal fat tissue distribution, over-activity of the sympathetic nervous system (SNS), metabolic abnormalities, and activation of the immune system. In children, PH usually presents with a typical phenotype of disturbed body composition, accelerated biological maturity, and subtle immunological and metabolic abnormalities. This stage of the disease is potentially reversible. However, long-lasting over-activity of the SNS and immuno-metabolic alterations usually lead to an irreversible stage of cardiovascular disease. We describe an intermediate phenotype of children with PH, showing that PH is associated with accelerated development, i.e., early premature aging of the immune, metabolic, and vascular systems. The associations and determinants of hypertensive organ damage, the principles of treatment, and the possibility of rejuvenation of the cardiovascular system are discussed. PMID:25724169

  3. Eribulin mesylate reduces tumor microenvironment abnormality by vascular remodeling in preclinical human breast cancer models

    PubMed Central

    Funahashi, Yasuhiro; Okamoto, Kiyoshi; Adachi, Yusuke; Semba, Taro; Uesugi, Mai; Ozawa, Yoichi; Tohyama, Osamu; Uehara, Taisuke; Kimura, Takayuki; Watanabe, Hideki; Asano, Makoto; Kawano, Satoshi; Tizon, Xavier; McCracken, Paul J; Matsui, Junji; Aoshima, Ken; Nomoto, Kenichi; Oda, Yoshiya

    2014-01-01

    Eribulin mesylate is a synthetic macrocyclic ketone analog of the marine sponge natural product halichondrin B and an inhibitor of microtubule dynamics. Some tubulin-binding drugs are known to have antivascular (antiangiogenesis or vascular-disrupting) activities that can target abnormal tumor vessels. Using dynamic contrast-enhanced MRI analyses, here we show that eribulin induces remodeling of tumor vasculature through a novel antivascular activity in MX-1 and MDA-MB-231 human breast cancer xenograft models. Vascular remodeling associated with improved perfusion was shown by Hoechst 33342 staining and by increased microvessel density together with decreased mean vascular areas and fewer branched vessels in tumor tissues, as determined by immunohistochemical staining for endothelial marker CD31. Quantitative RT-PCR analysis of normal host cells in the stroma of xenograft tumors showed that eribulin altered the expression of mouse (host) genes in angiogenesis signaling pathways controlling endothelial cell–pericyte interactions, and in the epithelial–mesenchymal transition pathway in the context of the tumor microenvironment. Eribulin also decreased hypoxia-associated protein expression of mouse (host) vascular endothelial growth factor by ELISA and human CA9 by immunohistochemical analysis. Prior treatment with eribulin enhanced the anti-tumor activity of capecitabine in the MDA-MB-231 xenograft model. These findings suggest that eribulin-induced remodeling of abnormal tumor vasculature leads to a more functional microenvironment that may reduce the aggressiveness of tumors due to elimination of inner tumor hypoxia. Because abnormal tumor microenvironments enhance both drug resistance and metastasis, the apparent ability of eribulin to reverse these aggressive characteristics may contribute to its clinical benefits. PMID:25060424

  4. Decreased MicroRNA Is Involved in the Vascular Remodeling Abnormalities in Chronic Kidney Disease (CKD)

    PubMed Central

    O'Neill, Kalisha D.; Chen, Xianming; Moorthi, Ranjani N.; Gattone, Vincent H.; Allen, Matthew R.; Moe, Sharon M.

    2013-01-01

    Patients with CKD have abnormal vascular remodeling that is a risk factor for cardiovascular disease. MicroRNAs (miRNAs) control mRNA expression intracellularly and are secreted into the circulation; three miRNAs (miR-125b, miR-145 and miR-155) are known to alter vascular smooth muscle cell (VSMC) proliferation and differentiation. We measured these vascular miRNAs in blood from 90 patients with CKD and found decreased circulating levels with progressive loss of eGFR by multivariate analyses. Expression of these vascular miRNAs miR-125b, miR-145, and miR-155 was decreased in the thoracic aorta in CKD rats compared to normal rats, with concordant changes in target genes of RUNX2, angiotensin II type I receptor (AT1R), and myocardin. Furthermore, the expression of miR-155 was negatively correlated with the quantity of calcification in the aorta, a process known to be preceded by vascular de-differentiation in these animals. We then examined the mechanisms of miRNA regulation in primary VSMC and found decreased expression of miR-125b, 145, and 155 in VSMC from rats with CKD compared to normal littermates but no alteration in DROSHA or DICER, indicating that the low levels of expression is not due to altered intracellular processing. Finally, overexpression of miR-155 in VSMC from CKD rats inhibited AT1R expression and decreased cellular proliferation supporting a direct effect of miR-155 on VSMC. In conclusion, we have found ex vivo and in vitro evidence for decreased expression of these vascular miRNA in CKD, suggesting that alterations in miRNAs may lead to the synthetic state of VSMC found in CKD. The decreased levels in the circulation may reflect decreased vascular release but more studies are needed to confirm this relationship. PMID:23717629

  5. Catechin averts experimental diabetes mellitus-induced vascular endothelial structural and functional abnormalities.

    PubMed

    Bhardwaj, Pooja; Khanna, Deepa; Balakumar, Pitchai

    2014-03-01

    Diabetes mellitus is associated with an induction of vascular endothelial dysfunction (VED), an initial event that could lead to the pathogenesis of atherosclerosis and hypertension. Previous studies showed that catechin, a key component of green tea, possesses vascular beneficial effects. We investigated the effect of catechin hydrate in diabetes mellitus-induced experimental vascular endothelial abnormalities (VEA). Streptozotocin (50 mg/kg, i.p., once) administration to rats produced diabetes mellitus, which subsequently induced VEA in 8 weeks by markedly attenuating acetylcholine-induced endothelium-dependent relaxation in the isolated aortic ring preparation, decreasing aortic and serum nitrite/nitrate concentrations and impairing aortic endothelial integrity. These abnormalities in diabetic rats were accompanied with elevated aortic superoxide anion generation and serum lipid peroxidation in addition to hyperglycemia. Catechin hydrate treatment (50 mg/kg/day p.o., 3 weeks) markedly prevented diabetes mellitus-induced VEA and vascular oxidative stress. Intriguingly, in vitro incubation of L-NAME (100 μM), an inhibitor of nitric oxide synthase, or Wortmannin (100 nM), a selective inhibitor of phosphatidylinositol 3-kinase (PI3K), markedly prevented catechin hydrate-induced improvement in acetylcholine-provoked endothelium-dependent relaxation in the diabetic rat aorta. Moreover, catechin hydrate treatment considerably reduced the elevated level of serum glucose in diabetic rats. In conclusion, catechin hydrate treatment prevents diabetes mellitus-induced VED through the activation of endothelial PI3K signal and subsequent activation of eNOS and generation of nitric oxide. In addition, reduction in high glucose, vascular oxidative stress, and lipid peroxidation might additionally contribute to catechin hydrate-associated prevention of diabetic VEA. PMID:24048981

  6. Pancytopenia in a Patient with Rendu-Osler-Weber Syndrome and Uncommon Vascular Abnormalities

    PubMed Central

    Gasbarrini, Antonio

    2016-01-01

    Rendu-Osler-Weber syndrome, or hereditary hemorrhagic teleangiectasia (HHT), is a rare autosomal dominant vascular disorder, characterized by multiple mucocutaneous teleangiectases with recurrent nasal and gastrointestinal bleedings and/or solid-organ arteriovenous shunts. We describe the first case to our knowledge of pancytopenia in a 53-year-old patient, with a known history of HHT and recurrent nasal and gastrointestinal bleedings, who was found to have a major splenic artery aneurysm and other uncommon vascular abnormalities. In the absence of other evident causes of pancytopenia, hypersplenism was diagnosed. The patient underwent coil embolization of the splenic artery aneurysm, followed by rapid and sustained increase of white blood cell and platelet count. Splenic artery aneurysms are extremely uncommon in HHT as only anecdotal cases have been reported to date. However, we believe that the aneurysm critically contributed to the progression of splenomegaly and the development of pancytopenia. PMID:27803822

  7. [Neural network detection of abnormalities in fed-batch fermentation].

    PubMed

    Li, Yun-Feng; Yuan, Jing-Qi

    2005-01-01

    During fermentation, it is often difficult to detect the abnormalities, for example, caused by contamination on-line. Instead, the faults were detected usually by off-line laboratory analysis or other ways, which in most cases, is too late to remedy the situation. In this paper, a simple three-layers BP network was used for the early prediction of the amount of product, based on the difference in prediction errors between normal and abnormal charges and other accessorial information, such as profit function and pH value. In addition, three indications characteristic to abnormal charge are incorporated in practical operation. The prediction for Cephalosporin C Fed-batch Fermentation in a Chinese pharmaceutical factory was studied in details as an example and the result shows the abnormal charge can be discovered early successfully using the method. PMID:15859337

  8. Classification of breast abnormalities using artificial neural network

    NASA Astrophysics Data System (ADS)

    Zaman, Nur Atiqah Kamarul; Rahman, Wan Eny Zarina Wan Abdul; Jumaat, Abdul Kadir; Yasiran, Siti Salmah

    2015-05-01

    Classification is the process of recognition, differentiation and categorizing objects into groups. Breast abnormalities are calcifications which are tumor markers that indicate the presence of cancer in the breast. The aims of this research are to classify the types of breast abnormalities using artificial neural network (ANN) classifier and to evaluate the accuracy performance using receiver operating characteristics (ROC) curve. The methods used in this research are ANN for breast abnormalities classifications and Canny edge detector as a feature extraction method. Previously the ANN classifier provides only the number of benign and malignant cases without providing information for specific cases. However in this research, the type of abnormality for each image can be obtained. The existing MIAS MiniMammographic database classified the mammogram images into three features only namely characteristic of background tissues, class of abnormality and radius of abnormality. However, in this research three other features are added-in. These three features are number of spots, area and shape of abnormalities. Lastly the performance of the ANN classifier is evaluated using ROC curve. It is found that ANN has an accuracy of 97.9% which is considered acceptable.

  9. Functional Human Vascular Network Generated in Photocrosslinkable Gelatin Methacrylate Hydrogels.

    PubMed

    Chen, Ying-Chieh; Lin, Ruei-Zeng; Qi, Hao; Yang, Yunzhi; Bae, Hojae; Melero-Martin, Juan M; Khademhosseini, Ali

    2012-05-23

    The generation of functional, 3D vascular networks is a fundamental prerequisite for the development of many future tissue engineering-based therapies. Current approaches in vascular network bioengineering are largely carried out using natural hydrogels as embedding scaffolds. However, most natural hydrogels present a poor mechanical stability and a suboptimal durability, which are critical limitations that hamper their widespread applicability. The search for improved hydrogels has become a priority in tissue engineering research. Here, the suitability of a photopolymerizable gelatin methacrylate (GelMA) hydrogel to support human progenitor cell-based formation of vascular networks is demonstrated. Using GelMA as the embedding scaffold, it is shown that 3D constructs containing human blood-derived endothelial colony-forming cells (ECFCs) and bone marrow-derived mesenchymal stem cells (MSCs) generate extensive capillary-like networks in vitro. These vascular structures contain distinct lumens that are formed by the fusion of ECFC intracellular vacuoles in a process of vascular morphogenesis. The process of vascular network formation is dependent on the presence of MSCs, which differentiate into perivascular cells occupying abluminal positions within the network. Importantly, it is shown that implantation of cell-laden GelMA hydrogels into immunodeficient mice results in a rapid formation of functional anastomoses between the bioengineered human vascular network and the mouse vasculature. Furthermore, it is shown that the degree of methacrylation of the GelMA can be used to modulate the cellular behavior and the extent of vascular network formation both in vitro and in vivo. These data suggest that GelMA hydrogels can be used for biomedical applications that require the formation of microvascular networks, including the development of complex engineered tissues.

  10. Hemangiomas, angiosarcomas, and vascular malformations represent the signaling abnormalities of pathogenic angiogenesis.

    PubMed

    Arbiser, J L; Bonner, M Y; Berrios, R L

    2009-11-01

    Angiogenesis is a major factor in the development of benign, inflammatory, and malignant processes of the skin. Endothelial cells are the effector cells of angiogenesis, and understanding their response to growth factors and inhibitors is critical to understanding the pathogenesis and treatment of skin disease. Hemangiomas, benign tumors of endothelial cells, represent the most common tumor of childhood. In our previous studies, we have found that tumor vasculature in human solid tumors expresses similarities in signaling to that of hemangiomas, making the knowledge of signaling in hemangiomas widely applicable. These similarities include expression of reactive oxygen, NFkB and akt in tumor vasculature. Furthermore, we have studied malignant vascular tumors, including hemangioendothelioma and angiosarcoma and have shown distinct signaling abnormalities in these tumors. The incidence of these tumors is expected to rise due to environmental insults, such as radiation and lumpectomy for breast cancer, dietary and industrial carcinogens (hepatic angiosarcoma), and chronic ultraviolet exposure and potential Agent Orange exposure. I hypothesize that hemangiomas, angiosarcomas, and vascular malformations represent the extremes of signaling abnormalities seen in pathogenic angiogenesis. PMID:19925405

  11. Reconciling abnormalities of brain network structure and function in schizophrenia.

    PubMed

    Fornito, Alex; Bullmore, Edward T

    2015-02-01

    Schizophrenia is widely regarded as a disorder of abnormal brain connectivity. Magnetic resonance imaging (MRI) suggests that patients show robust reductions of structural connectivity. However, corresponding changes in functional connectivity do not always follow, with increased functional connectivity being reported in many cases. Here, we consider different methodological and mechanistic accounts that might reconcile these apparently contradictory findings and argue that increased functional connectivity in schizophrenia likely represents a pathophysiological dysregulation of brain activity arising from abnormal neurodevelopmental wiring of structural connections linking putative hub regions of association cortex to other brain areas. Elucidating the pathophysiological significance of connectivity abnormalities in schizophrenia will be contingent on better understanding how network structure shapes and constrains function.

  12. Mechanisms of gas exchange abnormality in patients with chronic obliterative pulmonary vascular disease.

    PubMed Central

    Dantzker, D R; Bower, J S

    1979-01-01

    We have examined the mechanisms of abnormal gas exchange in seven patients with chronic obliteration of the pulmonary vascular bed secondary to recurrent pulmonary emboli or idiopathic pulmonary hypertension. All of the patients had a widened alveolar-arterial oxygen gradient and four were significantly hypoxemic with arterial partial presssures of oxygen less than 80 torr. Using the technique of multiple inert gas elimination, we found that ventilation-perfusion (VA/Q) relationships were only minimally abnormal with a mean of 10% (range, 2--19%) of cardiac output perfusing abnormal units. These units consisted of shunt and units with VA/Q ratios less than 0.1. In addition, the dead space was found to be normal in each patient. There was no evidence for diffusion impairment, and the widened alveolar-arterial oxygen gradient was completely explained by VA/ inequality. Significant hypoxemia occurred only when VA/Q inequality was combined with a low mixed venous oxygen content. PMID:479367

  13. Temporal modulation of collective cell behavior controls vascular network topology

    PubMed Central

    Kur, Esther; Kim, Jiha; Tata, Aleksandra; Comin, Cesar H; Harrington, Kyle I; Costa, Luciano da F; Bentley, Katie; Gu, Chenghua

    2016-01-01

    Vascular network density determines the amount of oxygen and nutrients delivered to host tissues, but how the vast diversity of densities is generated is unknown. Reiterations of endothelial-tip-cell selection, sprout extension and anastomosis are the basis for vascular network generation, a process governed by the VEGF/Notch feedback loop. Here, we find that temporal regulation of this feedback loop, a previously unexplored dimension, is the key mechanism to determine vascular density. Iterating between computational modeling and in vivo live imaging, we demonstrate that the rate of tip-cell selection determines the length of linear sprout extension at the expense of branching, dictating network density. We provide the first example of a host tissue-derived signal (Semaphorin3E-Plexin-D1) that accelerates tip cell selection rate, yielding a dense network. We propose that temporal regulation of this critical, iterative aspect of network formation could be a general mechanism, and additional temporal regulators may exist to sculpt vascular topology. DOI: http://dx.doi.org/10.7554/eLife.13212.001 PMID:26910011

  14. [Vascular networks of the periphery of the finger nail].

    PubMed

    Sick, H; Wolfram-Gabel, R

    The vascular networks of the periphery of the nail of the finger are studied on fingers of adults, fetus and newborns, by injecting the vascular system with gelatinous Indian ink. The nail is an avascular horny structure, partially covered with the nail fold. It is lying on a nail bed which prolonges forwards with the hyponychium. Each part of the nail apparatus (nail fold, matricial and unmatricial parts of the nail bed, hyponychium) presents a characteristic network which is tributary of dorsal collaterals arising from the digital palmar vessels and from their arcades. These networks are papillar, pseudopapillar, reticular and subdermical. The morphology and density of these networks vary according to their localisation and are superimposed with the histological variations of the different parts of the nail apparatus. Thus the matricial part of the nail bed shows a poor vascularization. It corresponds to the germinative part of the nail and is responsible of the color of the lunula. The unmatricial part of the nail bed and the hyponychium have dense vascular networks with glomi.

  15. Temporal modulation of collective cell behavior controls vascular network topology.

    PubMed

    Kur, Esther; Kim, Jiha; Tata, Aleksandra; Comin, Cesar H; Harrington, Kyle I; Costa, Luciano da F; Bentley, Katie; Gu, Chenghua

    2016-01-01

    Vascular network density determines the amount of oxygen and nutrients delivered to host tissues, but how the vast diversity of densities is generated is unknown. Reiterations of endothelial-tip-cell selection, sprout extension and anastomosis are the basis for vascular network generation, a process governed by the VEGF/Notch feedback loop. Here, we find that temporal regulation of this feedback loop, a previously unexplored dimension, is the key mechanism to determine vascular density. Iterating between computational modeling and in vivo live imaging, we demonstrate that the rate of tip-cell selection determines the length of linear sprout extension at the expense of branching, dictating network density. We provide the first example of a host tissue-derived signal (Semaphorin3E-Plexin-D1) that accelerates tip cell selection rate, yielding a dense network. We propose that temporal regulation of this critical, iterative aspect of network formation could be a general mechanism, and additional temporal regulators may exist to sculpt vascular topology.

  16. Abnormal Growth Factor/Cytokine Network in Gastric Cancer

    PubMed Central

    2008-01-01

    Gastric cancer cells express a broad spectrum of the growth factor/cytokine receptor systems that organize the complex interaction between cancer cells and stromal cells in tumor microenvironment, which confers cell growth, apoptosis, morphogenesis, angiogenesis, progression and metastasis. However, these abnormal growth factor/cytokine networks differ in the two histological types of gastric cancer. Importantly, activation of nuclear factor-kB pathway by Helicobacter pylori infection may act as a key player for induction of growth factor/cytokine networks in gastritis and pathogenesis of gastric cancer. Better understanding of these events will no doubt provide new approaches for biomarkers of diagnosis and effective therapeutic targeting of gastric cancer. PMID:19308687

  17. Abnormalities associated with progressive aortic vascular dysfunction in chronic kidney disease

    PubMed Central

    Ameer, Omar Z.; Boyd, Rochelle; Butlin, Mark; Avolio, Alberto P.; Phillips, Jacqueline K.

    2015-01-01

    Increased stiffness of large arteries in chronic kidney disease (CKD) has significant clinical implications. This study investigates the temporal development of thoracic aortic dysfunction in a rodent model of CKD, the Lewis polycystic kidney (LPK) rat. Animals aged 12 and 18 weeks were studied alongside age-matched Lewis controls (total n = 94). LPK rodents had elevated systolic blood pressure, left ventricular hypertrophy and progressively higher plasma creatinine and urea. Relative to Lewis controls, LPK exhibited reduced maximum aortic vasoconstriction (Rmax) to noradrenaline at 12 and 18 weeks, and to K+ (12 weeks). Sensitivity to noradrenaline was greater in 18-week-old LPK vs. age matched Lewis (effective concentration 50%: 24 × 10−9 ± 78 × 10−10 vs. 19 × 10−8 ± 49 × 10−9, P < 0.05). Endothelium-dependent (acetylcholine) and -independent (sodium nitroprusside) relaxation was diminished in LPK, declining with age (12 vs. 18 weeks Rmax: 80 ± 8% vs. 57 ± 9% and 92 ± 6% vs. 70 ± 9%, P < 0.05, respectively) in parallel with the decline in renal function. L-Arginine restored endothelial function in LPK, and L-NAME blunted acetylcholine relaxation in all groups. Impaired nitric oxide synthase (NOS) activity was recovered with L-Arginine plus L-NAME in 12, but not 18-week-old LPK. Aortic calcification was increased in LPK rats, as was collagen I/III, fibronectin and NADPH-oxidase subunit p47 (phox) mRNAs. Overall, our observations indicate that the vascular abnormalities associated with CKD are progressive in nature, being characterized by impaired vascular contraction and relaxation responses, concurrent with the development of endothelial dysfunction, which is likely driven by evolving deficits in NO signaling. PMID:26042042

  18. Mechanical regulation of vascular network formation in engineered matrices.

    PubMed

    Lesman, Ayelet; Rosenfeld, Dekel; Landau, Shira; Levenberg, Shulamit

    2016-01-15

    Generation of vessel networks within engineered tissues is critical for integration and perfusion of the implanted tissue in vivo. The effect of mechanical cues in guiding and stabilizing the vessels has begun to attract marked interest. This review surveys the impact of mechanical cues on formation of vascular networks in 2D and 3D gel matrices. We give less emphasis to regulation of endothelial monolayers and single endothelial cells. Several vascularization models have consistently found that the stress generated in the gel, and encountered by embedded cells, control various aspects of vascular network formation, including sprouting, branching, alignment, and vessel maturation. This internal stress is generated by cell contractile forces, and is balanced by gel stiffness and boundary constrains imposed on the gel. Actin and myosin II are key molecular players in controlling initiation of vessel sprouting and branching morphogenesis. Additionally, the impact of external mechanical cues on tissue vascularization, and studies supporting the notion that mechanical forces regulate vascularization in the live animal are reviewed.

  19. Hydrogel Bioprinted Microchannel Networks for Vascularization of Tissue Engineering Constructs

    PubMed Central

    Bertassoni, Luiz E.; Cecconi, Martina; Manoharan, Vijayan; Nikkhah, Mehdi; Hjortnaes, Jesper; Cristino, Ana Luiza; Barabaschi, Giada; Demarchi, Danilo; Dokmeci, Mehmet R.; Yang, Yunzhi; Khademhosseini, Ali

    2014-01-01

    Vascularization remains a critical challenge in tissue engineering. The development of vascular networks within densely populated and metabolically functional tissues facilitate transport of nutrients and removal of waste products, thus preserving cellular viability over a long period of time. Despite tremendous progress in fabricating complex tissue constructs in the past few years, approaches for controlled vascularization within hydrogel based engineered tissue constructs have remained limited. Here, we report a three dimensional (3D) micromolding technique utilizing bioprinted agarose template fibers to fabricate microchannel networks with various architectural features within photo cross linkable hydrogel constructs. Using the proposed approach, we were able to successfully embed functional and perfusable microchannels inside methacrylated gelatin (GelMA), star poly (ethylene glycol-co-lactide) acrylate (SPELA), poly (ethylene glycol) dimethacrylate (PEGDMA) and poly (ethylene glycol) diacrylate (PEGDA) hydrogels at different concentrations. In particular, GelMA hydrogels were used as a model to demonstrate the functionality of the fabricated vascular networks in improving mass transport, cellular viability and differentiation within the cell-laden tissue constructs. In addition, successful formation of endothelial monolayers within the fabricated channels was confirmed. Overall, our proposed strategy represents an effective technique for vascularization of hydrogel constructs with useful applications in tissue engineering and organs on a chip. PMID:24860845

  20. Hydrogel bioprinted microchannel networks for vascularization of tissue engineering constructs.

    PubMed

    Bertassoni, Luiz E; Cecconi, Martina; Manoharan, Vijayan; Nikkhah, Mehdi; Hjortnaes, Jesper; Cristino, Ana Luiza; Barabaschi, Giada; Demarchi, Danilo; Dokmeci, Mehmet R; Yang, Yunzhi; Khademhosseini, Ali

    2014-07-01

    Vascularization remains a critical challenge in tissue engineering. The development of vascular networks within densely populated and metabolically functional tissues facilitate transport of nutrients and removal of waste products, thus preserving cellular viability over a long period of time. Despite tremendous progress in fabricating complex tissue constructs in the past few years, approaches for controlled vascularization within hydrogel based engineered tissue constructs have remained limited. Here, we report a three dimensional (3D) micromolding technique utilizing bioprinted agarose template fibers to fabricate microchannel networks with various architectural features within photocrosslinkable hydrogel constructs. Using the proposed approach, we were able to successfully embed functional and perfusable microchannels inside methacrylated gelatin (GelMA), star poly(ethylene glycol-co-lactide) acrylate (SPELA), poly(ethylene glycol) dimethacrylate (PEGDMA) and poly(ethylene glycol) diacrylate (PEGDA) hydrogels at different concentrations. In particular, GelMA hydrogels were used as a model to demonstrate the functionality of the fabricated vascular networks in improving mass transport, cellular viability and differentiation within the cell-laden tissue constructs. In addition, successful formation of endothelial monolayers within the fabricated channels was confirmed. Overall, our proposed strategy represents an effective technique for vascularization of hydrogel constructs with useful applications in tissue engineering and organs on a chip.

  1. Three-dimensional imaging and quantification of complex vascular networks

    NASA Astrophysics Data System (ADS)

    Barber, Paul R.; Ameer-Beg, Simon M.; Vojnovic, Borivoj; Hodgkiss, Richard J.; Tozer, Gillian M.; Wilson, John; Prise, Vivien E.

    2003-10-01

    The understanding of tumour angiogenesis and response to vascular-targeted drugs are of increasing interest in cancer research. We present 3D images of the in vivo tumour vasculature captured utilising multi-photon microscopy together with the results of manual and semi-automated delineation of the vascular network using novel in-house-developed software and algorithms. The software presented is aimed at aiding in these investigations and other problems where linear or dendritic structures are to be delineated from 3D data sets. A new algorithm, CHARM, based on a compact Hough transform and the formation of a radial map, has been used to automatically locate vessel centres and measure diameters. The robustness of this algorithm to image smoothing and noise has been investigated. Statistical information characterising the network in terms of vascular parameters as well as more complex analyses, such as fractal dimension, are now possible and examples are presented.

  2. Fluid shear stress as a regulator of gene expression in vascular cells: possible correlations with diabetic abnormalities

    NASA Technical Reports Server (NTRS)

    Papadaki, M.; Eskin, S. G.; Ruef, J.; Runge, M. S.; McIntire, L. V.

    1999-01-01

    Diabetes mellitus is associated with increased frequency, severity and more rapid progression of cardiovascular diseases. Metabolic perturbations from hyperglycemia result in disturbed endothelium-dependent relaxation, activation of coagulation pathways, depressed fibrinolysis, and other abnormalities in vascular homeostasis. Atherosclerosis is localized mainly at areas of geometric irregularity at which blood vessels branch, curve and change diameter, and where blood is subjected to sudden changes in velocity and/or direction of flow. Shear stress resulting from blood flow is a well known modulator of vascular cell function. This paper presents what is currently known regarding the molecular mechanisms responsible for signal transduction and gene regulation in vascular cells exposed to shear stress. Considering the importance of the hemodynamic environment of vascular cells might be vital to increasing our understanding of diabetes.

  3. Dynamics of VEGF matrix-retention in vascular network patterning

    NASA Astrophysics Data System (ADS)

    Köhn-Luque, A.; de Back, W.; Yamaguchi, Y.; Yoshimura, K.; Herrero, M. A.; Miura, T.

    2013-12-01

    Vascular endothelial growth factor (VEGF) is a central regulator of blood vessel morphogenesis, although its role in patterning of endothelial cells into vascular networks is not fully understood. It has been suggested that binding of soluble VEGF to extracellular matrix components causes spatially restricted cues that guide endothelial cells into network patterns. Yet, current evidence for such a mechanism remains indirect. In this study, we quantitatively analyse the dynamics of VEGF retention in a controlled in vitro situation of human umbilical vascular endothelial cells (HUVECs) in Matrigel. We show that fluorescent VEGF accumulates in pericellular areas and colocalizes with VEGF binding molecules. Analysis of fluorescence recovery after photobleaching reveals that binding/unbinding to matrix molecules dominates VEGF dynamics in the pericellular region. Computational simulations using our experimental measurements of kinetic parameters show that matrix retention of chemotactic signals can lead to the formation of reticular cellular networks on a realistic timescale. Taken together, these results show that VEGF binds to matrix molecules in proximity of HUVECs in Matrigel, and suggest that bound VEGF drives vascular network patterning.

  4. Abnormal Brain Network Organization in Body Dysmorphic Disorder

    PubMed Central

    Arienzo, Donatello; Leow, Alex; Brown, Jesse A; Zhan, Liang; GadElkarim, Johnson; Hovav, Sarit; Feusner, Jamie D

    2013-01-01

    Body dysmorphic disorder (BDD) is characterized by preoccupation with misperceived defects of appearance, causing significant distress and disability. Previous studies suggest abnormalities in information processing characterized by greater local relative to global processing. The purpose of this study was to probe whole-brain and regional white matter network organization in BDD, and to relate this to specific metrics of symptomatology. We acquired diffusion-weighted 34-direction MR images from 14 unmedicated participants with DSM-IV BDD and 16 healthy controls, from which we conducted whole-brain deterministic diffusion tensor imaging tractography. We then constructed white matter structural connectivity matrices to derive whole-brain and regional graph theory metrics, which we compared between groups. Within the BDD group, we additionally correlated these metrics with scores on psychometric measures of BDD symptom severity as well as poor insight/delusionality. The BDD group showed higher whole-brain mean clustering coefficient than controls. Global efficiency negatively correlated with BDD symptom severity. The BDD group demonstrated greater edge betweenness centrality for connections between the anterior temporal lobe and the occipital cortex, and between bilateral occipital poles. This represents the first brain network analysis in BDD. Results suggest disturbances in whole brain structural topological organization in BDD, in addition to correlations between clinical symptoms and network organization. There is also evidence of abnormal connectivity between regions involved in lower-order visual processing and higher-order visual and emotional processing, as well as interhemispheric visual information transfer. These findings may relate to disturbances in information processing found in previous studies. PMID:23322186

  5. Enzymatic regulation of functional vascular networks using gelatin hydrogels.

    PubMed

    Chuang, Chia-Hui; Lin, Ruei-Zeng; Tien, Han-Wen; Chu, Ya-Chun; Li, Yen-Cheng; Melero-Martin, Juan M; Chen, Ying-Chieh

    2015-06-01

    To manufacture tissue engineering-based functional tissues, scaffold materials that can be sufficiently vascularized to mimic the functionality and complexity of native tissues are needed. Currently, vascular network bioengineering is largely carried out using natural hydrogels as embedding scaffolds, but most natural hydrogels have poor mechanical stability and durability, factors that critically limit their widespread use. In this study, we examined the suitability of gelatin-phenolic hydroxyl (gelatin-Ph) hydrogels that can be enzymatically crosslinked, allowing tuning of the storage modulus and the proteolytic degradation rate, for use as injectable hydrogels to support the human progenitor cell-based formation of a stable and mature vascular network. Porcine gelatin-Ph hydrogels were found to be cytocompatible with human blood-derived endothelial colony-forming cells and white adipose tissue-derived mesenchymal stem cells, resulting in >87% viability, and cell proliferation and spreading could be modulated by using hydrogels with different proteolytic degradability and stiffness. In addition, gelatin was extracted from mouse dermis and murine gelatin-Ph hydrogels were prepared. Importantly, implantation of human cell-laden porcine or murine gelatin-Ph hydrogels into immunodeficient mice resulted in the rapid formation of functional anastomoses between the bioengineered human vascular network and the mouse vasculature. Furthermore, the degree of enzymatic crosslinking of the gelatin-Ph hydrogels could be used to modulate cell behavior and the extent of vascular network formation in vivo. Our report details a technique for the synthesis of gelatin-Ph hydrogels from allogeneic or xenogeneic dermal skin and suggests that these hydrogels can be used for biomedical applications that require the formation of microvascular networks, including the development of complex engineered tissues.

  6. Enzymatic regulation of functional vascular networks using gelatin hydrogels

    PubMed Central

    Chuang, Chia-Hui; Lin, Ruei-Zeng; Tien, Han-Wen; Chu, Ya-Chun; Li, Yen-Cheng; Melero-Martin, Juan M.; Chen, Ying-Chieh

    2015-01-01

    To manufacture tissue engineering-based functional tissues, scaffold materials that can be sufficiently vascularized to mimic the functionality and complexity of native tissues are needed. Currently, vascular network bioengineering is largely carried out using natural hydrogels as embedding scaffolds, but most natural hydrogels have poor mechanical stability and durability, factors that critically limit their widespread use. In this study, we examined the suitability of gelatin-phenolic hydroxyl (gelatin-Ph) hydrogels that can be enzymatically crosslinked, allowing tuning of the storage modulus and the proteolytic degradation rate, for use as injectable hydrogels to support the human progenitor cell-based formation of a stable and mature vascular network. Porcine gelatin-Ph hydrogels were found to be cytocompatible with human blood-derived endothelial colony-forming cells and white adipose tissue-derived mesenchymal stem cells, resulting in >87% viability, and cell proliferation and spreading could be modulated by using hydrogels with different proteolytic degradability and stiffness. In addition, gelatin was extracted from mouse dermis and murine gelatin-Ph hydrogels were prepared. Importantly, implantation of human cell-laden porcine or murine gelatin-Ph hydrogels into immunodeficient mice resulted in the rapid formation of functional anastomoses between the bioengineered human vascular network and the mouse vasculature. Furthermore, the degree of enzymatic crosslinking of the gelatin-Ph hydrogels could be used to modulate cell behavior and the extent of vascular network formation in vivo. Our report details a technique for the synthesis of gelatin-Ph hydrogels from allogeneic or xenogeneic dermal skin and suggests that these hydrogels can be used for biomedical applications that require the formation of microvascular networks, including the development of complex engineered tissues. PMID:25749296

  7. Quantification of blood flow and topology in developing vascular networks.

    PubMed

    Kloosterman, Astrid; Hierck, Beerend; Westerweel, Jerry; Poelma, Christian

    2014-01-01

    Since fluid dynamics plays a critical role in vascular remodeling, quantification of the hemodynamics is crucial to gain more insight into this complex process. Better understanding of vascular development can improve prediction of the process, and may eventually even be used to influence the vascular structure. In this study, a methodology to quantify hemodynamics and network structure of developing vascular networks is described. The hemodynamic parameters and topology are derived from detailed local blood flow velocities, obtained by in vivo micro-PIV measurements. The use of such detailed flow measurements is shown to be essential, as blood vessels with a similar diameter can have a large variation in flow rate. Measurements are performed in the yolk sacs of seven chicken embryos at two developmental stages between HH 13+ and 17+. A large range of flow velocities (1 µm/s to 1 mm/s) is measured in blood vessels with diameters in the range of 25-500 µm. The quality of the data sets is investigated by verifying the flow balances in the branching points. This shows that the quality of the data sets of the seven embryos is comparable for all stages observed, and the data is suitable for further analysis with known accuracy. When comparing two subsequently characterized networks of the same embryo, vascular remodeling is observed in all seven networks. However, the character of remodeling in the seven embryos differs and can be non-intuitive, which confirms the necessity of quantification. To illustrate the potential of the data, we present a preliminary quantitative study of key network topology parameters and we compare these with theoretical design rules.

  8. Diabetic retinopathy: retina-specific methods for maintenance of diabetic rodents and evaluation of vascular histopathology and molecular abnormalities

    PubMed Central

    Veenstra, Alexander; Liu, Haitao; Lee, Chieh Allen; Du, Yunpeng; Tang, Jie; Kern, Timothy S.

    2015-01-01

    Diabetic retinopathy is a major cause of visual impairment, which continues to increase in prevalence as more and more people develop diabetes. Despite the importance of vision, the retina is one of the smallest tissues in the body, and specialized techniques to study the retinopathy have been developed. This chapter will summarize several methods used to (i) induce diabetes, (ii) maintain the diabetic animals throughout the months required for the development of typical vascular histopathology, (iii) evaluate vascular histopathology of diabetic retinopathy, and (iv) quantitate abnormalities implicated in the development of the retinopathy. PMID:26331759

  9. A new approach to blood flow simulation in vascular networks.

    PubMed

    Tamaddon, Houman; Behnia, Mehrdad; Behnia, Masud; Kritharides, Leonard

    2016-01-01

    A proper analysis of blood flow is contingent upon accurate modelling of the branching pattern and vascular geometry of the network of interest. It is challenging to reconstruct the entire vascular network of any organ experimentally, in particular the pulmonary vasculature, because of its very high number of vessels, complexity of the branching pattern and poor accessibility in vivo. The objective of our research is to develop an innovative approach for the reconstruction of the full pulmonary vascular tree from available morphometric data. Our method consists of the use of morphometric data on those parts of the pulmonary vascular tree that are too small to reconstruct by medical imaging methods. This method is a three-step technique that reconstructs the entire pulmonary arterial tree down to the capillary bed. Vessels greater than 2 mm are reconstructed from direct volume and surface analysis using contrast-enhanced computed tomography. Vessels smaller than 2 mm are reconstructed from available morphometric and distensibility data and rearranged by applying Murray's laws. Implementation of morphometric data to reconstruct the branching pattern and applying Murray's laws to every vessel bifurcation simultaneously leads to an accurate vascular tree reconstruction. The reconstruction algorithm generates full arterial tree topography down to the first capillary bifurcation. Geometry of each order of the vascular tree is generated separately to minimize the construction and simulation time. The node-to-node connectivity along with the diameter and length of every vessel segment is established and order numbers, according to the diameter-defined Strahler system, are assigned. In conclusion, the present model provides a morphological foundation for future analysis of blood flow in the pulmonary circulation.

  10. Engineering of human hepatic tissue with functional vascular networks.

    PubMed

    Takebe, Takanori; Koike, Naoto; Sekine, Keisuke; Fujiwara, Ryoji; Amiya, Takeru; Zheng, Yun-Wen; Taniguchi, Hideki

    2014-01-01

    Although absolute organ shortage highlights the needs of alternative organ sources for regenerative medicine, the generation of a three-dimensional (3D) and complex vital organ, such as well-vascularized liver, remains a challenge. To this end, tissue engineering holds great promise; however, this approach is significantly limited by the failure of early vascularization in vivo after implantation. Here, we established a stable 3D in vitro pre-vascularization platform to generate human hepatic tissue after implantation in vivo. Human fetal liver cells (hFLCs) were mixed with human umbilical vein endothelial cells (HUVECs) and mesenchymal stem cells (hMSCs) and were implanted into a collagen/fibronectin matrix composite that was used as a 3-D carrier. After a couple of days, the fluorescent HUVECs developed premature vascular networks in vitro, which were stabilized by hMSCs. The establishment of functional vessels inside the pre-vascularized constructs was proven using dextran infusion studies after implantation under a transparency cranial window. Furthermore, dynamic morphological changes during embryonic liver cell maturation were intravitaly quantified with high-resolution confocal microscope analysis. The engineered human hepatic tissue demonstrated multiple liver-specific features, both structural and functional. Our new techniques discussed here can be implemented in future clinical uses and industrial uses, such as drug testing. PMID:24451152

  11. Engineering of human hepatic tissue with functional vascular networks

    PubMed Central

    Takebe, Takanori; Koike, Naoto; Sekine, Keisuke; Fujiwara, Ryoji; Amiya, Takeru; Zheng, Yun-Wen; Taniguchi, Hideki

    2014-01-01

    Although absolute organ shortage highlights the needs of alternative organ sources for regenerative medicine, the generation of a three-dimensional (3D) and complex vital organ, such as well-vascularized liver, remains a challenge. To this end, tissue engineering holds great promise; however, this approach is significantly limited by the failure of early vascularization in vivo after implantation. Here, we established a stable 3D in vitro pre-vascularization platform to generate human hepatic tissue after implantation in vivo. Human fetal liver cells (hFLCs) were mixed with human umbilical vein endothelial cells (HUVECs) and mesenchymal stem cells (hMSCs) and were implanted into a collagen/fibronectin matrix composite that was used as a 3-D carrier. After a couple of days, the fluorescent HUVECs developed premature vascular networks in vitro, which were stabilized by hMSCs. The establishment of functional vessels inside the pre-vascularized constructs was proven using dextran infusion studies after implantation under a transparency cranial window. Furthermore, dynamic morphological changes during embryonic liver cell maturation were intravitaly quantified with high-resolution confocal microscope analysis. The engineered human hepatic tissue demonstrated multiple liver-specific features, both structural and functional. Our new techniques discussed here can be implemented in future clinical uses and industrial uses, such as drug testing. PMID:24451152

  12. Engineering of human hepatic tissue with functional vascular networks.

    PubMed

    Takebe, Takanori; Koike, Naoto; Sekine, Keisuke; Fujiwara, Ryoji; Amiya, Takeru; Zheng, Yun-Wen; Taniguchi, Hideki

    2014-01-01

    Although absolute organ shortage highlights the needs of alternative organ sources for regenerative medicine, the generation of a three-dimensional (3D) and complex vital organ, such as well-vascularized liver, remains a challenge. To this end, tissue engineering holds great promise; however, this approach is significantly limited by the failure of early vascularization in vivo after implantation. Here, we established a stable 3D in vitro pre-vascularization platform to generate human hepatic tissue after implantation in vivo. Human fetal liver cells (hFLCs) were mixed with human umbilical vein endothelial cells (HUVECs) and mesenchymal stem cells (hMSCs) and were implanted into a collagen/fibronectin matrix composite that was used as a 3-D carrier. After a couple of days, the fluorescent HUVECs developed premature vascular networks in vitro, which were stabilized by hMSCs. The establishment of functional vessels inside the pre-vascularized constructs was proven using dextran infusion studies after implantation under a transparency cranial window. Furthermore, dynamic morphological changes during embryonic liver cell maturation were intravitaly quantified with high-resolution confocal microscope analysis. The engineered human hepatic tissue demonstrated multiple liver-specific features, both structural and functional. Our new techniques discussed here can be implemented in future clinical uses and industrial uses, such as drug testing.

  13. Vascular-like network prepared using hollow hydrogel microfibers.

    PubMed

    Takei, Takayuki; Kitazono, Zyunpei; Ozuno, Yoshihiro; Yoshinaga, Takuma; Nishimata, Hiroto; Yoshida, Masahiro

    2016-03-01

    One major challenge in the field of tissue engineering was the creation of volumetric tissues and organs in vitro. To achieve this goal, the development of a three-dimensional vascular-like network that extended throughout the tissue-engineered construct was essential to supply sufficient oxygen and nutrients to all of the cells in the constructs. For sufficient oxygenation and nutrition of the tissue-engineered constructs, the distance between each microvessel-like channel in the network should ideally be within 100-200 μm. In addition, the medium or blood should be perfused through the microchannels as soon as possible after the seeding of cells into the templates (scaffolds) of the constructs. In the present study, we proposed a novel technique for fabricating an engineered vascular-like network that satisfied these two requirements. The network comprised assembled hollow alginate hydrogel microfibers with mammalian cells enclosed in the gel portions. We controlled the distance between each flow microchannel (hollow core portions and interspace of the microfibers) to be within 150 μm by using microfibers with a gel thickness of approximately 50 μm. Furthermore, we confirmed that medium could be perfused into the flow channels quickly (within 10 min) after immobilization of the cells in the assembly. A human hepatoblastoma cell line (HepG2) proliferated in the gel portions of the microfibers and maintained their specific function during perfusion culture for 7 days. These results showed that the novel vascular-like networks fabricated here had the potential to allow the creation of volumetric tissues in vitro. PMID:26199226

  14. Abnormalities in hyperpolarized (129)Xe magnetic resonance imaging and spectroscopy in two patients with pulmonary vascular disease.

    PubMed

    Dahhan, Talal; Kaushik, Shiv S; He, Mu; Mammarappallil, Joseph G; Tapson, Victor F; McAdams, Holman P; Sporn, Thomas A; Driehuys, Bastiaan; Rajagopal, Sudarshan

    2016-03-01

    The diagnosis of pulmonary vascular disease (PVD) is usually based on hemodynamic and/or clinical criteria. Noninvasive imaging of the heart and proximal vasculature can also provide useful information. An alternate approach to such criteria in the diagnosis of PVD is to image the vascular abnormalities in the lungs themselves. Hyperpolarized (HP) (129)Xe magnetic resonance imaging (MRI) is a novel technique for assessing abnormalities in ventilation and gas exchange in the lungs. We applied this technique to two patients for whom there was clinical suspicion of PVD. Two patients who had significant hypoxemia and dyspnea with no significant abnormalities on computed tomography imaging or ventilation-perfusion scan and only mild or borderline pulmonary arterial hypertension at catheterization were evaluated. They underwent HP (129)Xe imaging and subsequently had tissue diagnosis obtained from lung pathology. In both patients, HP (129)Xe imaging demonstrated normal ventilation but markedly decreased gas transfer to red blood cells with focal defects on imaging, a pattern distinct from those previously described for idiopathic pulmonary fibrosis or obstructive lung disease. Pathology on both patients later demonstrated severe PVD. These findings suggest that HP (129)Xe MRI may be useful in the diagnosis of PVD and monitoring response to therapy. Further studies are required to determine its sensitivity and specificity in these settings. PMID:27162620

  15. Construction of Large-Volume Tissue Mimics with 3D Functional Vascular Networks

    PubMed Central

    Kang, Tae-Yun; Hong, Jung Min; Jung, Jin Woo; Kang, Hyun-Wook; Cho, Dong-Woo

    2016-01-01

    We used indirect stereolithography (SL) to form inner-layered fluidic networks in a porous scaffold by introducing a hydrogel barrier on the luminal surface, then seeded the networks separately with human umbilical vein endothelial cells and human lung fibroblasts to form a tissue mimic containing vascular networks. The artificial vascular networks provided channels for oxygen transport, thus reducing the hypoxic volume and preventing cell death. The endothelium of the vascular networks significantly retarded the occlusion of channels during whole-blood circulation. The tissue mimics have the potential to be used as an in vitro platform to examine the physiologic and pathologic phenomena through vascular architecture. PMID:27228079

  16. Physical determinants of vascular network remodeling during tumor growth.

    PubMed

    Welter, M; Rieger, H

    2010-10-01

    The process in which a growing tumor transforms a hierarchically organized arterio-venous blood vessel network into a tumor specific vasculature is analyzed with a theoretical model. The physical determinants of this remodeling involve the morphological and hydrodynamic properties of the initial network, generation of new vessels (sprouting angiogenesis), vessel dilation (circumferential growth), vessel regression, tumor cell proliferation and death, and the interdependence of these processes via spatio-temporal changes of blood flow parameters, oxygen/nutrient supply and growth factor concentration fields. The emerging tumor vasculature is non-hierarchical, compartmentalized into well-characterized zones, displays a complex geometry with necrotic zones and "hot spots" of increased vascular density and blood flow of varying size, and transports drug injections efficiently. Implications for current theoretical views on tumor-induced angiogenesis are discussed.

  17. Cues for cellular assembly of vascular elastin networks

    NASA Astrophysics Data System (ADS)

    Kothapalli, Chandrasekhar R.

    LOX protein synthesis (2.5-fold); these cues also enhanced deposition of mature elastic fibers (˜1 mum diameter) within these cultures. Interestingly, instead of copper salt addition, even release of Cu 2+ ions (˜0.1 M) from copper nanoparticles (400 ng/mL), concurrent with HA oligomers, promoted crosslinking of elastin into mature matrix, with multiple bundles of highly-crosslinked elastin fiber formation observed (diameter ˜200-500 nm). These results strongly attest to the potential individual and combined benefits of these cues to faithful elastin matrix regeneration by healthy, patient-derived cells within tissue-engineered vascular constructs. When these cues (TGF-beta1 and HA oligomers) were added to TNF-alpha-stimulated SMC cultures, model cell culture systems mimicking phenotypically-altered cells within aneurysms, they upregulated elastin matrix production, organized elastin protein into fibers, and simultaneously stabilized this matrix by attenuating production of elastolytic enzymes. Similarly these cues also attenuated inflammatory cytokines release within cells isolated from induced-aortic aneurysms in rats, and significantly upregulated elastin synthesis and matrix formation by upregulating LOX and desmosine protein amounts. The cues were also highly effective in organizing the elastin into fibrous matrix structures mimicking the native elastin deposition process. The outcomes of this study might be of tremendous use in optimizing design of HA constructs to modulate vascular healing and matrix synthesis following revascularization, and in enabling repair of elastin networks within diseased or inflammatory (aneurysmal) adult vascular tissues.

  18. Motion-related vascular abnormalities at the craniocervical junction: illustrative case series and literature review.

    PubMed

    Ravindra, Vijay M; Neil, Jayson A; Mazur, Marcus D; Park, Min S; Couldwell, William T; Taussky, Philipp

    2015-04-01

    The craniocervical junction (CCJ) functions within a complicated regional anatomy necessary to protect and support vital neurovascular structures. In select instances, vascular pathology can be attributed to this complicated interplay of motion and structure found within this narrow space. The authors report 3 cases of complex vascular pathology related to motion at the CCJ and detail the management of these cases. Two cases involved posterior circulation vascular compression syndromes, and one case involved a vascular anomaly and its relation to aneurysm formation and rupture. The patient in Case 1 was a 66-year-old man with a history of syncopal episodes resulting from the bilateral vertebral artery becoming occluded when he rotated his head. Successful microsurgical decompression at the skull base resulted in patent bilateral vertebral artery V3 segments upon head movement in all directions. The patient in Case 2 was a 53-year-old woman who underwent elective resection of a right temporal meningioma and who experienced postoperative drowsiness, dysphagia, and mild right-arm ataxia. Subsequent MRI demonstrated bilateral posterior inferior cerebel-lar artery (PICA) strokes. Cerebral angiography showed a single PICA, of extradural origin, supplying both cerebellar hemispheres. The PICA exhibited dynamic extradural compression when the patient rotated her head; the bilateral PICA strokes were due to head rotation during surgical positioning. In Case 3, a 37-year-old woman found unconscious in her home had diffuse subarachnoid hemorrhage and evidence of a right PICA aneurysm. A right far-lateral craniectomy was performed for aneurysm clipping, and she was found to have a dissecting aneurysm with an associated PICA originating extradurally. There was a shearing phenomenon of the extradural PICA along the dura of the foramen magnum, and this microtraumatic stress imposed on the vessel resulted in a dissecting aneurysm. This series of complex and unusual cases

  19. Mechanical Stress Induces Remodeling of Vascular Networks in Growing Leaves.

    PubMed

    Bar-Sinai, Yohai; Julien, Jean-Daniel; Sharon, Eran; Armon, Shahaf; Nakayama, Naomi; Adda-Bedia, Mokhtar; Boudaoud, Arezki

    2016-04-01

    Differentiation into well-defined patterns and tissue growth are recognized as key processes in organismal development. However, it is unclear whether patterns are passively, homogeneously dilated by growth or whether they remodel during tissue expansion. Leaf vascular networks are well-fitted to investigate this issue, since leaves are approximately two-dimensional and grow manyfold in size. Here we study experimentally and computationally how vein patterns affect growth. We first model the growing vasculature as a network of viscoelastic rods and consider its response to external mechanical stress. We use the so-called texture tensor to quantify the local network geometry and reveal that growth is heterogeneous, resembling non-affine deformations in composite materials. We then apply mechanical forces to growing leaves after veins have differentiated, which respond by anisotropic growth and reorientation of the network in the direction of external stress. External mechanical stress appears to make growth more homogeneous, in contrast with the model with viscoelastic rods. However, we reconcile the model with experimental data by incorporating randomness in rod thickness and a threshold in the rod growth law, making the rods viscoelastoplastic. Altogether, we show that the higher stiffness of veins leads to their reorientation along external forces, along with a reduction in growth heterogeneity. This process may lead to the reinforcement of leaves against mechanical stress. More generally, our work contributes to a framework whereby growth and patterns are coordinated through the differences in mechanical properties between cell types. PMID:27074136

  20. Mechanical Stress Induces Remodeling of Vascular Networks in Growing Leaves

    PubMed Central

    Bar-Sinai, Yohai; Julien, Jean-Daniel; Sharon, Eran; Armon, Shahaf; Nakayama, Naomi; Adda-Bedia, Mokhtar; Boudaoud, Arezki

    2016-01-01

    Differentiation into well-defined patterns and tissue growth are recognized as key processes in organismal development. However, it is unclear whether patterns are passively, homogeneously dilated by growth or whether they remodel during tissue expansion. Leaf vascular networks are well-fitted to investigate this issue, since leaves are approximately two-dimensional and grow manyfold in size. Here we study experimentally and computationally how vein patterns affect growth. We first model the growing vasculature as a network of viscoelastic rods and consider its response to external mechanical stress. We use the so-called texture tensor to quantify the local network geometry and reveal that growth is heterogeneous, resembling non-affine deformations in composite materials. We then apply mechanical forces to growing leaves after veins have differentiated, which respond by anisotropic growth and reorientation of the network in the direction of external stress. External mechanical stress appears to make growth more homogeneous, in contrast with the model with viscoelastic rods. However, we reconcile the model with experimental data by incorporating randomness in rod thickness and a threshold in the rod growth law, making the rods viscoelastoplastic. Altogether, we show that the higher stiffness of veins leads to their reorientation along external forces, along with a reduction in growth heterogeneity. This process may lead to the reinforcement of leaves against mechanical stress. More generally, our work contributes to a framework whereby growth and patterns are coordinated through the differences in mechanical properties between cell types. PMID:27074136

  1. Abnormal thallium kinetics in postoperative coarctation of the aorta: evidence for diffuse hypertension-induced vascular pathology

    SciTech Connect

    Kimball, B.P.; Shurvell, B.L.; Mildenberger, R.R.; Houle, S.; McLaughlin, P.R.

    1986-03-01

    After operative correction of congenital coarctation of the aorta, patients continue to have excess cardiovascular mortality, including manifestations of ischemic heart disease. Previous morphologic studies support the concept of direct hypertensive vascular injury in these patients. To determine whether abnormalities of myocardial perfusion were present in an asymptomatic group of patients with coarctation repair, 18 men and 9 women with a mean age of 26 years (range 19 to 41) were studied between 2 and 25 years after operative correction. Stress electrocardiography and quantitative thallium imaging by a circumferential profile technique were used. These patients were compared with a normal group, statistically defined as having a less than 1% prevalence of significant obstructive coronary artery disease. The postoperative coarctation group demonstrated a reduction in global thallium redistribution in each view analyzed. As compared with findings in the control subjects, thallium washout in the anterior view (41.9 versus 48.6%, p = 0.02) and left anterior oblique projection (40.5 versus 48.2%, p = 0.007) was significantly diminished. Although the postoperative coarctation group had a lower thallium redistribution rate in the lateral view (41.4 versus 46.3%, p = 0.09) this difference did not reach statistical significance because of the intrinsic variability of this projection. Plots of the median percent thallium washout revealed independence from circumferential profile angle, indicating global abnormalities in perfusion. No correlation between clinical variables and thallium kinetics could be established, suggesting marked individual variability in the development of this vascular lesion. The observation of abnormal thallium kinetics in patients with coarctation repair may have consequences for long-term follow-up and therapy.

  2. Vascular Dynamics Aid a Coupled Neurovascular Network Learn Sparse Independent Features: A Computational Model.

    PubMed

    Philips, Ryan T; Chhabria, Karishma; Chakravarthy, V Srinivasa

    2016-01-01

    Cerebral vascular dynamics are generally thought to be controlled by neural activity in a unidirectional fashion. However, both computational modeling and experimental evidence point to the feedback effects of vascular dynamics on neural activity. Vascular feedback in the form of glucose and oxygen controls neuronal ATP, either directly or via the agency of astrocytes, which in turn modulates neural firing. Recently, a detailed model of the neuron-astrocyte-vessel system has shown how vasomotion can modulate neural firing. Similarly, arguing from known cerebrovascular physiology, an approach known as "hemoneural hypothesis" postulates functional modulation of neural activity by vascular feedback. To instantiate this perspective, we present a computational model in which a network of "vascular units" supplies energy to a neural network. The complex dynamics of the vascular network, modeled by a network of oscillators, turns neurons ON and OFF randomly. The informational consequence of such dynamics is explored in the context of an auto-encoder network. In the proposed model, each vascular unit supplies energy to a subset of hidden neurons of an autoencoder network, which constitutes its "projective field." Neurons that receive adequate energy in a given trial have reduced threshold, and thus are prone to fire. Dynamics of the vascular network are governed by changes in the reconstruction error of the auto-encoder network, interpreted as the neuronal demand. Vascular feedback causes random inactivation of a subset of hidden neurons in every trial. We observe that, under conditions of desynchronized vascular dynamics, the output reconstruction error is low and the feature vectors learnt are sparse and independent. Our earlier modeling study highlighted the link between desynchronized vascular dynamics and efficient energy delivery in skeletal muscle. We now show that desynchronized vascular dynamics leads to efficient training in an auto-encoder neural network. PMID

  3. Vascular Dynamics Aid a Coupled Neurovascular Network Learn Sparse Independent Features: A Computational Model

    PubMed Central

    Philips, Ryan T.; Chhabria, Karishma; Chakravarthy, V. Srinivasa

    2016-01-01

    Cerebral vascular dynamics are generally thought to be controlled by neural activity in a unidirectional fashion. However, both computational modeling and experimental evidence point to the feedback effects of vascular dynamics on neural activity. Vascular feedback in the form of glucose and oxygen controls neuronal ATP, either directly or via the agency of astrocytes, which in turn modulates neural firing. Recently, a detailed model of the neuron-astrocyte-vessel system has shown how vasomotion can modulate neural firing. Similarly, arguing from known cerebrovascular physiology, an approach known as “hemoneural hypothesis” postulates functional modulation of neural activity by vascular feedback. To instantiate this perspective, we present a computational model in which a network of “vascular units” supplies energy to a neural network. The complex dynamics of the vascular network, modeled by a network of oscillators, turns neurons ON and OFF randomly. The informational consequence of such dynamics is explored in the context of an auto-encoder network. In the proposed model, each vascular unit supplies energy to a subset of hidden neurons of an autoencoder network, which constitutes its “projective field.” Neurons that receive adequate energy in a given trial have reduced threshold, and thus are prone to fire. Dynamics of the vascular network are governed by changes in the reconstruction error of the auto-encoder network, interpreted as the neuronal demand. Vascular feedback causes random inactivation of a subset of hidden neurons in every trial. We observe that, under conditions of desynchronized vascular dynamics, the output reconstruction error is low and the feature vectors learnt are sparse and independent. Our earlier modeling study highlighted the link between desynchronized vascular dynamics and efficient energy delivery in skeletal muscle. We now show that desynchronized vascular dynamics leads to efficient training in an auto-encoder neural

  4. Smooth muscle calcium and endothelium-derived relaxing factor in the abnormal vascular responses of acute renal failure.

    PubMed Central

    Conger, J D; Robinette, J B; Schrier, R W

    1988-01-01

    Abnormal renovascular reactivity, characterized by paradoxical vasoconstriction to a reduction in renal perfusion pressure (RPP) in the autoregulatory range, increased sensitivity to renal nerve stimulation (RNS), and loss of vasodilatation to acetylcholine have all been demonstrated in ischemic acute renal failure (ARF). To determine if ischemic injury alters vascular contractility by increasing smooth muscle cell calcium or calcium influx, the renal blood flow (RBF) response to reductions in RPP within the autoregulatory range and to RNS were tested before and after a 90-min intrarenal infusion of verapamil or diltiazem in 7-d ischemic ARF rats. Both calcium entry blockers, verapamil and diltiazem, blocked the aberrant vasoconstrictor response to a reduction in RPP and RNS (both P less than 0.001). In a second series of experiments the potential role of an ischemia-induced endothelial injury and of the absence of endothelium-derived relaxing factor (EDRF) production were examined to explain the lack of vasodilatation to acetylcholine. Acetylcholine, bradykinin (a second EDRF-dependent vasodilator), or prostacyclin, an EDRF-independent vasodilator, was infused intrarenally for 90 min, and RBF responses to a reduction in RPP and RNS were tested in 7-d ischemic ARF rats. Neither acetylcholine nor bradykinin caused vasodilatation or altered the slope of the relationship between RBF and RPP. By contrast, prostacyclin increased RBF (P less than 0.001), but did not change the vascular response to changes in RPP. It was concluded that the abnormal pressor sensitivity to a reduction in RPP and RNS was due to changes in renovascular smooth muscle cell calcium activity that could be blocked by calcium entry blockers. A lack of response to EDRF-dependent vasodilators, as a result of ischemic endothelial injury, may contribute to the increased pressor sensitivity of the renal vessels. PMID:3261301

  5. Abnormalities in large scale functional networks in unmedicated patients with schizophrenia and effects of risperidone

    PubMed Central

    Kraguljac, Nina Vanessa; White, David Matthew; Hadley, Jennifer Ann; Visscher, Kristina; Knight, David; ver Hoef, Lawrence; Falola, Blessing; Lahti, Adrienne Carol

    2015-01-01

    Objective To describe abnormalities in large scale functional networks in unmedicated patients with schizophrenia and to examine effects of risperidone on networks. Material and methods 34 unmedicated patients with schizophrenia and 34 matched healthy controls were enrolled in this longitudinal study. We collected resting state functional MRI data with a 3T scanner at baseline and six weeks after they were started on risperidone. In addition, a group of 19 healthy controls were scanned twice six weeks apart. Four large scale networks, the dorsal attention network, executive control network, salience network, and default mode network were identified with seed based functional connectivity analyses. Group differences in connectivity, as well as changes in connectivity over time, were assessed on the group's participant level functional connectivity maps. Results In unmedicated patients with schizophrenia we found resting state connectivity to be increased in the dorsal attention network, executive control network, and salience network relative to control participants, but not the default mode network. Dysconnectivity was attenuated after six weeks of treatment only in the dorsal attention network. Baseline connectivity in this network was also related to clinical response at six weeks of treatment with risperidone. Conclusions Our results demonstrate abnormalities in large scale functional networks in patients with schizophrenia that are modulated by risperidone only to a certain extent, underscoring the dire need for development of novel antipsychotic medications that have the ability to alleviate symptoms through attenuation of dysconnectivity. PMID:26793436

  6. Connectomics and graph theory analyses: Novel insights into network abnormalities in epilepsy.

    PubMed

    Gleichgerrcht, Ezequiel; Kocher, Madison; Bonilha, Leonardo

    2015-11-01

    The assessment of neural networks in epilepsy has become increasingly relevant in the context of translational research, given that localized forms of epilepsy are more likely to be related to abnormal function within specific brain networks, as opposed to isolated focal brain pathology. It is notable that variability in clinical outcomes from epilepsy treatment may be a reflection of individual patterns of network abnormalities. As such, network endophenotypes may be important biomarkers for the diagnosis and treatment of epilepsy. Despite its exceptional potential, measuring abnormal networks in translational research has been thus far constrained by methodologic limitations. Fortunately, recent advancements in neuroscience, particularly in the field of connectomics, permit a detailed assessment of network organization, dynamics, and function at an individual level. Data from the personal connectome can be assessed using principled forms of network analyses based on graph theory, which may disclose patterns of organization that are prone to abnormal dynamics and epileptogenesis. Although the field of connectomics is relatively new, there is already a rapidly growing body of evidence to suggest that it can elucidate several important and fundamental aspects of abnormal networks to epilepsy. In this article, we provide a review of the emerging evidence from connectomics research regarding neural network architecture, dynamics, and function related to epilepsy. We discuss how connectomics may bring together pathophysiologic hypotheses from conceptual and basic models of epilepsy and in vivo biomarkers for clinical translational research. By providing neural network information unique to each individual, the field of connectomics may help to elucidate variability in clinical outcomes and open opportunities for personalized medicine approaches to epilepsy. Connectomics involves complex and rich data from each subject, thus collaborative efforts to enable the

  7. Sensory-related neural activity regulates the structure of vascular networks in the cerebral cortex

    PubMed Central

    Lacoste, Baptiste; Comin, Cesar H.; Ben-Zvi, Ayal; Kaeser, Pascal S.; Xu, Xiaoyin; Costa, Luciano da F.; Gu, Chenghua

    2014-01-01

    SUMMARY Neurovascular interactions are essential for proper brain function. While the effect of neural activity on cerebral blood flow has been extensively studied, whether neural activity influences vascular patterning remains elusive. Here, we demonstrate that neural activity promotes the formation of vascular networks in the early postnatal mouse barrel cortex. Using a combination of genetics, imaging, and computational tools to allow simultaneous analysis of neuronal and vascular components, we found that vascular density and branching were decreased in the barrel cortex when sensory input was reduced by either a complete deafferentation, a genetic impairment of neurotransmitter release at thalamocortical synapses, or a selective reduction of sensory-related neural activity by whisker plucking. In contrast, enhancement of neural activity by whisker stimulation led to an increase in vascular density and branching. The finding that neural activity is necessary and sufficient to trigger alterations of vascular networks reveals a novel feature of neurovascular interactions. PMID:25155955

  8. Possible involvement of PPARγ-associated eNOS signaling activation in rosuvastatin-mediated prevention of nicotine-induced experimental vascular endothelial abnormalities.

    PubMed

    Kathuria, Sonam; Mahadevan, Nanjaian; Balakumar, Pitchai

    2013-02-01

    Nicotine exposure via cigarette smoking and tobacco chewing is associated with vascular complications. The present study investigated the effect of rosuvastatin in nicotine (2 mg/kg/day, i.p., 4 weeks)-induced vascular endothelial dysfunction (VED) in rats. The development of VED was assessed by employing isolated aortic ring preparation and estimating aortic and serum nitrite/nitrate concentration. Further, scanning electron microscopy and hematoxylin-eosin staining of thoracic aorta were performed to assess the vascular endothelial integrity. Moreover, oxidative stress was assessed by estimating aortic superoxide anion generation and serum thiobarbituric acid-reactive substances. The nicotine administration produced VED by markedly reducing acetylcholine-induced endothelium-dependent relaxation, impairing the integrity of vascular endothelium, decreasing aortic and serum nitrite/nitrate concentration, increasing oxidative stress, and inducing lipid alteration. However, treatment with rosuvastatin (10 mg/kg/day, i.p., 4 weeks) markedly attenuated nicotine-induced vascular endothelial abnormalities, oxidative stress, and lipid alteration. Interestingly, the co-administration of peroxisome proliferator-activated receptor γ (PPARγ) antagonist, GW9662 (1 mg/kg/day, i.p., 2 weeks) submaximally, significantly prevented rosuvastatin-induced improvement in vascular endothelial integrity, endothelium-dependent relaxation, and nitrite/nitrate concentration in rats administered nicotine. However, GW9662 co-administration did not affect rosuvastatin-associated vascular anti-oxidant and lipid-lowering effects. The incubation of aortic ring, isolated from rosuvastatin-treated nicotine-administered rats, with L-NAME (100 μM), an inhibitor of nitric oxide synthase (NOS), significantly attenuated rosuvastatin-induced improvement in acetylcholine-induced endothelium-dependent relaxation. Rosuvastatin prevents nicotine-induced vascular endothelial abnormalities by activating

  9. Investigating water transport through the xylem network in vascular plants.

    PubMed

    Kim, Hae Koo; Park, Joonghyuk; Hwang, Ildoo

    2014-04-01

    Our understanding of physical and physiological mechanisms depends on the development of advanced technologies and tools to prove or re-evaluate established theories, and test new hypotheses. Water flow in land plants is a fascinating phenomenon, a vital component of the water cycle, and essential for life on Earth. The cohesion-tension theory (CTT), formulated more than a century ago and based on the physical properties of water, laid the foundation for our understanding of water transport in vascular plants. Numerous experimental tools have since been developed to evaluate various aspects of the CTT, such as the existence of negative hydrostatic pressure. This review focuses on the evolution of the experimental methods used to study water transport in plants, and summarizes the different ways to investigate the diversity of the xylem network structure and sap flow dynamics in various species. As water transport is documented at different scales, from the level of single conduits to entire plants, it is critical that new results be subjected to systematic cross-validation and that findings based on different organs be integrated at the whole-plant level. We also discuss the functional trade-offs between optimizing hydraulic efficiency and maintaining the safety of the entire transport system. Furthermore, we evaluate future directions in sap flow research and highlight the importance of integrating the combined effects of various levels of hydraulic regulation.

  10. High compliance vascular grafts based on semi-interpenetrating networks

    PubMed Central

    Dempsey, David K.; Nezarati, Roya M.; Mackey, Calvin E.

    2014-01-01

    Current synthetic vascular grafts have poor patency rates in small diameter applications (<6 mm) due to intimal hyperplasia arising from a compliance mismatch between the graft and native vasculature. Enormous efforts have focused on improving biomechanical properties; however, polymeric grafts are often constrained by an inverse relationship between burst pressure and compliance. We have developed a new, semi-interpenetrating network (semi-IPN) approach to improve compliance without sacrificing burst pressure. The effects of heat treatment on graft morphology, fiber architecture, and resultant biomechanical properties are presented. In addition, biomechanical properties after equilibration at physiological temperature were investigated in relation to polyurethane microstructure to better predict in vivo performance. Compliance values as high as 9.2 ± 2.7 %/mmHg x 10−4 were observed for the semi-IPN graft while also maintaining high burst pressure, 1780 ± 230 mm Hg. The high compliance of these heat-treated poly(carbonate urethane) (PCU) and semi-IPN grafts is expected to improve long-term patency rates beyond even saphenous vein autografts by preventing intimal hyperplasia. The fundamental structure-property relationships gained from this work may also be utilized to advance biomedical device designs based on thermoplastic polyurethanes. PMID:25601822

  11. An automated computational framework for retinal vascular network labeling and branching order analysis.

    PubMed

    Huang, Yue; Zhang, Jun; Huang, Yunying

    2012-09-01

    Changes in retinal vascular morphology are well known as predictive clinical signs of many diseases such as hypertension, diabetes and so on. Computer-aid image processing and analysis for retinal vessels in fundus images are effective and efficient in clinical diagnosis instead of tedious manual labeling and measurement. An automated computational framework for retinal vascular network labeling and analysis is presented in this work. The framework includes 1) detecting and locating the optic disc; 2) tracking the vessel centerline from detected seed points and linking the breaks after tracing; 3) extracting all the retinal vascular trees and identifying all the significant points; and 4) classifying terminal points into starting points and ending points based on the information of optic disc location, and finally assigning branch order for each extracted vascular tree in the image. All the modules in the framework are fully automated. Based on the results, morphological analysis is then applied to achieve geometrical and topological features based on branching order for one individual vascular tree or for the vascular network through the retinal vascular network in the images. Validation and experiments on the public DRIVE database have demonstrated that the proposed framework is a novel approach to analyze and study the vascular network pattern, and may offer new insights to the diagnosis of retinopathy.

  12. Cases of limb-body wall complex: Early amnion rupture, vascular disruption, or abnormal splitting of the embryo?

    PubMed Central

    Crespo, Frank; Pinar, Halit; Kostadinov, Stefan

    2012-01-01

    We report two cases of limb-body wall complex (LBWC), also known as body stalk anomaly, a rare form of body wall defect incompatible with life. The first case was identified during a level II ultrasound examination performed at 7 wk gestational age. The delivery was by breech extraction at 39 wk and 4 days. The second case was delivered by spontaneous vaginal delivery at 35 wk and 5 days. Karyotype analysis was normal in both fetuses. The phenotype of LBWC is variable, but commonly identified features include: exencephaly, limb defects, and either facial clefts or thoraco-abdominoschisis. The exact etiology remains uncertain, as the disorder has been regarded as sporadic with low recurrence. Vascular disruption during early embryogenesis, early amnion rupture, abnormal splitting of the embryo, and failure of amnion fusion have been implicated in the pathogenesis of LBWC. A role for possible gene mutation and maternal use of alcohol, tobacco, or illicit drugs has also been suggested. Detailed ultrasonography along with biochemical screening may allow for early detection.

  13. Cases of limb-body wall complex: Early amnion rupture, vascular disruption, or abnormal splitting of the embryo?

    PubMed

    Crespo, Frank; Pinar, Halit; Kostadinov, Stefan

    2012-12-01

    We report two cases of limb-body wall complex (LBWC), also known as body stalk anomaly, a rare form of body wall defect incompatible with life. The first case was identified during a level II ultrasound examination performed at 7 wk gestational age. The delivery was by breech extraction at 39 wk and 4 days. The second case was delivered by spontaneous vaginal delivery at 35 wk and 5 days. Karyotype analysis was normal in both fetuses. The phenotype of LBWC is variable, but commonly identified features include: exencephaly, limb defects, and either facial clefts or thoraco-abdominoschisis. The exact etiology remains uncertain, as the disorder has been regarded as sporadic with low recurrence. Vascular disruption during early embryogenesis, early amnion rupture, abnormal splitting of the embryo, and failure of amnion fusion have been implicated in the pathogenesis of LBWC. A role for possible gene mutation and maternal use of alcohol, tobacco, or illicit drugs has also been suggested. Detailed ultrasonography along with biochemical screening may allow for early detection. PMID:27625829

  14. Cases of limb-body wall complex: Early amnion rupture, vascular disruption, or abnormal splitting of the embryo?

    PubMed

    Crespo, Frank; Pinar, Halit; Kostadinov, Stefan

    2012-12-01

    We report two cases of limb-body wall complex (LBWC), also known as body stalk anomaly, a rare form of body wall defect incompatible with life. The first case was identified during a level II ultrasound examination performed at 7 wk gestational age. The delivery was by breech extraction at 39 wk and 4 days. The second case was delivered by spontaneous vaginal delivery at 35 wk and 5 days. Karyotype analysis was normal in both fetuses. The phenotype of LBWC is variable, but commonly identified features include: exencephaly, limb defects, and either facial clefts or thoraco-abdominoschisis. The exact etiology remains uncertain, as the disorder has been regarded as sporadic with low recurrence. Vascular disruption during early embryogenesis, early amnion rupture, abnormal splitting of the embryo, and failure of amnion fusion have been implicated in the pathogenesis of LBWC. A role for possible gene mutation and maternal use of alcohol, tobacco, or illicit drugs has also been suggested. Detailed ultrasonography along with biochemical screening may allow for early detection.

  15. Dipeptidyl peptidase-4 inhibition by gemigliptin prevents abnormal vascular remodeling via NF-E2-related factor 2 activation.

    PubMed

    Choi, Seung Hee; Park, Sungmi; Oh, Chang Joo; Leem, Jaechan; Park, Keun-Gyu; Lee, In-Kyu

    2015-10-01

    Dipeptidyl peptidase-4 (DPP-4) inhibitors exert a potent anti-hyperglycemic effect and reduce cardiovascular risk in type 2 diabetic patients. Several studies have shown that DPP-4 inhibitors including sitagliptin have beneficial effects in atherosclerosis and cardiac infarction involving reactive oxygen species. Here, we show that gemigliptin can directly attenuate the abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) via enhanced NF-E2-related factor 2 (Nrf2) activity. Gemigliptin dramatically prevented ligation injury-induced neointimal hyperplasia in mouse carotid arteries. Likewise, the proliferation of primary VSMCs was significantly attenuated by gemigliptin in a dose-dependent manner consistent with a decrease in phospho-Rb, resulting in G1 cell cycle arrest. We found that gemigliptin enhanced Nrf2 activity not only by mRNA expression, but also by increasing Keap1 proteosomal degradation by p62, leading to the induction of Nrf2 target genes such as HO-1 and NQO1. The anti-proliferative role of gemigliptin disappeared with DPP-4 siRNA knockdown, indicating that the endogenous DPP-4 in VSMCs contributed to the effect of gemigliptin. In addition, gemigliptin diminished TNF-α-mediated cell adhesion molecules such as MCP-1 and VCAM-1 and reduced MMP2 activity in VSMCs. Taken together, our data indicate that gemigliptin exerts a preventative effect on the proliferation and migration of VSMCs via Nrf2. PMID:26187356

  16. Transdermal regulation of vascular network bioengineering using a photopolymerizable methacrylated gelatin hydrogel.

    PubMed

    Lin, Ruei-Zeng; Chen, Ying-Chieh; Moreno-Luna, Rafael; Khademhosseini, Ali; Melero-Martin, Juan M

    2013-09-01

    The search for hydrogel materials compatible with vascular morphogenesis is an active area of investigation in tissue engineering. One candidate material is methacrylated gelatin (GelMA), a UV-photocrosslinkable hydrogel that is synthesized by adding methacrylate groups to the amine-containing side-groups of gelatin. GelMA hydrogels containing human endothelial colony-forming cells (ECFCs) and mesenchymal stem cells (MSCs) can be photopolymerized ex vivo and then surgically transplanted in vivo as a means to generate vascular networks. However, the full clinical potential of GelMA will be best captured by enabling minimally invasive implantation and in situ polymerization. In this study, we demonstrated the feasibility of bioengineering human vascular networks inside GelMA constructs that were first subcutaneously injected into immunodeficient mice while in liquid form, and then rapidly crosslinked via transdermal exposure to UV light. These bioengineered vascular networks developed within 7 days, formed functional anastomoses with the host vasculature, and were uniformly distributed throughout the constructs. Most notably, we demonstrated that the vascularization process can be directly modulated by adjusting the initial exposure time to UV light (15-45 s range), with constructs displaying progressively less vascular density and smaller average lumen size as the degree of GelMA crosslinking was increased. Our studies support the use of GelMA in its injectable form, followed by in situ transdermal photopolymerization, as a preferable means to deliver cells in applications that require the formation of vascular networks in vivo.

  17. Transdermal regulation of vascular network bioengineering using a photopolymerizable methacrylated gelatin hydrogel

    PubMed Central

    Lin, Ruei-Zeng; Chen, Ying-Chieh; Moreno-Luna, Rafael; Khademhosseini, Ali; Melero-Martin, Juan M.

    2013-01-01

    The search for hydrogel materials compatible with vascular morphogenesis is an active area of investigation in tissue engineering. One candidate material is methacrylated gelatin (GelMA), a UV-photocrosslinkable hydrogel that is synthesized by adding methacrylate groups to the amine-containing side-groups of gelatin. GelMA hydrogels containing human endothelial colony-forming cells (ECFCs) and mesenchymal stem cells (MSCs) can be photopolymerized ex vivo and then surgically transplanted in vivo as a means to generate vascular networks. However, the full clinical potential of GelMA will be best captured by enabling minimally invasive implantation and in situ polymerization. In this study, we demonstrated the feasibility of bioengineering human vascular networks inside GelMA constructs that were first subcutaneously injected into immunodeficient mice while in liquid form, and then rapidly crosslinked via transdermal exposure to UV light. These bioengineered vascular networks developed within 7 days, formed functional anastomoses with the host vasculature, and were uniformly distributed throughout the constructs. Most notably, we demonstrated that the vascularization process can be directly modulated by adjusting the initial exposure time to UV light (15–45 s range), with constructs displaying progressively less vascular density and smaller average lumen size as the degree of GelMA crosslinking was increased. Our studies support the use of GelMA in its injectable form, followed by in situ transdermal photopolymerization, as a preferable means to deliver cells in applications that require the formation of vascular networks in vivo. PMID:23773819

  18. Rapid casting of patterned vascular networks for perfusable engineered 3D tissues

    PubMed Central

    Miller, Jordan S.; Stevens, Kelly R.; Yang, Michael T.; Baker, Brendon M.; Nguyen, Duc-Huy T.; Cohen, Daniel M.; Toro, Esteban; Chen, Alice A.; Galie, Peter A.; Yu, Xiang; Chaturvedi, Ritika; Bhatia, Sangeeta N.; Chen, Christopher S.

    2012-01-01

    In the absence of perfusable vascular networks, three-dimensional (3D) engineered tissues densely populated with cells quickly develop a necrotic core [1]. Yet the lack of a general approach to rapidly construct such networks remains a major challenge for 3D tissue culture [2–4]. Here, we 3D printed rigid filament networks of carbohydrate glass, and used them as a cytocompatible sacrificial template in engineered tissues containing living cells to generate cylindrical networks which could be lined with endothelial cells and perfused with blood under high-pressure pulsatile flow. Because this simple vascular casting approach allows independent control of network geometry, endothelialization, and extravascular tissue, it is compatible with a wide variety of cell types, synthetic and natural extracellular matrices (ECMs), and crosslinking strategies. We also demonstrated that the perfused vascular channels sustained the metabolic function of primary rat hepatocytes in engineered tissue constructs that otherwise exhibited suppressed function in their core. PMID:22751181

  19. A generative modeling approach to connectivity-Electrical conduction in vascular networks.

    PubMed

    Hald, Bjørn Olav

    2016-06-21

    The physiology of biological structures is inherently dynamic and emerges from the interaction and assembly of large collections of small entities. The extent of coupled entities complicates modeling and increases computational load. Here, microvascular networks are used to present a novel generative approach to connectivity based on the observation that biological organization is hierarchical and composed of a limited set of building blocks, i.e. a vascular network consists of blood vessels which in turn are composed by one or more cell types. Fast electrical communication is crucial to synchronize vessel tone across the vast distances within a network. We hypothesize that electrical conduction capacity is delimited by the size of vascular structures and connectivity of the network. Generation and simulation of series of dynamical models of electrical spread within vascular networks of different size and composition showed that (1) Conduction is enhanced in models harboring long and thin endothelial cells that couple preferentially along the longitudinal axis. (2) Conduction across a branch point depends on endothelial connectivity between branches. (3) Low connectivity sub-networks are more sensitive to electrical perturbations. In summary, the capacity for electrical signaling in microvascular networks is strongly shaped by the morphology and connectivity of vascular (particularly endothelial) cells. While the presented software can be used by itself or as a starting point for more sophisticated models of vascular dynamics, the generative approach can be applied to other biological systems, e.g. nervous tissue, the lymphatics, or the biliary system.

  20. Morphogenesis of 3D vascular networks is regulated by tensile forces.

    PubMed

    Rosenfeld, Dekel; Landau, Shira; Shandalov, Yulia; Raindel, Noa; Freiman, Alina; Shor, Erez; Blinder, Yaron; Vandenburgh, Herman H; Mooney, David J; Levenberg, Shulamit

    2016-03-22

    Understanding the forces controlling vascular network properties and morphology can enhance in vitro tissue vascularization and graft integration prospects. This work assessed the effect of uniaxial cell-induced and externally applied tensile forces on the morphology of vascular networks formed within fibroblast and endothelial cell-embedded 3D polymeric constructs. Force intensity correlated with network quality, as verified by inhibition of force and of angiogenesis-related regulators. Tensile forces during vessel formation resulted in parallel vessel orientation under static stretching and diagonal orientation under cyclic stretching, supported by angiogenic factors secreted in response to each stretch protocol. Implantation of scaffolds bearing network orientations matching those of host abdominal muscle tissue improved graft integration and the mechanical properties of the implantation site, a critical factor in repair of defects in this area. This study demonstrates the regulatory role of forces in angiogenesis and their capacities in vessel structure manipulation, which can be exploited to improve scaffolds for tissue repair.

  1. Base structure consisting of an endothelialized vascular-tree network and hepatocytes for whole liver engineering.

    PubMed

    Shirakigawa, Nana; Takei, Takayuki; Ijima, Hiroyuki

    2013-12-01

    Reconstructed liver has been desired as a liver substitute for transplantation. However, reconstruction of a whole liver has not been achieved because construction of a vascular network at an organ scale is very difficult. We focused on decellularized liver (DC-liver) as an artificial scaffold for the construction of a hierarchical vascular network. In this study, we obtained DC-liver and the tubular network structure in which both portal vein and hepatic vein systems remained intact. Furthermore, endothelialization of the tubular structure in DC-liver was achieved, which prevented blood leakage from the tubular structure. In addition, hepatocytes suspended in a collagen sol were injected from the surroundings using a syringe as a suitable procedure for liver cell inoculation. In summary, we developed a base structure consisting of an endothelialized vascular-tree network and hepatocytes for whole liver engineering.

  2. Morphogenesis of 3D vascular networks is regulated by tensile forces.

    PubMed

    Rosenfeld, Dekel; Landau, Shira; Shandalov, Yulia; Raindel, Noa; Freiman, Alina; Shor, Erez; Blinder, Yaron; Vandenburgh, Herman H; Mooney, David J; Levenberg, Shulamit

    2016-03-22

    Understanding the forces controlling vascular network properties and morphology can enhance in vitro tissue vascularization and graft integration prospects. This work assessed the effect of uniaxial cell-induced and externally applied tensile forces on the morphology of vascular networks formed within fibroblast and endothelial cell-embedded 3D polymeric constructs. Force intensity correlated with network quality, as verified by inhibition of force and of angiogenesis-related regulators. Tensile forces during vessel formation resulted in parallel vessel orientation under static stretching and diagonal orientation under cyclic stretching, supported by angiogenic factors secreted in response to each stretch protocol. Implantation of scaffolds bearing network orientations matching those of host abdominal muscle tissue improved graft integration and the mechanical properties of the implantation site, a critical factor in repair of defects in this area. This study demonstrates the regulatory role of forces in angiogenesis and their capacities in vessel structure manipulation, which can be exploited to improve scaffolds for tissue repair. PMID:26951667

  3. Morphogenesis of 3D vascular networks is regulated by tensile forces

    PubMed Central

    Rosenfeld, Dekel; Landau, Shira; Shandalov, Yulia; Raindel, Noa; Freiman, Alina; Shor, Erez; Blinder, Yaron; Vandenburgh, Herman H.; Mooney, David J.; Levenberg, Shulamit

    2016-01-01

    Understanding the forces controlling vascular network properties and morphology can enhance in vitro tissue vascularization and graft integration prospects. This work assessed the effect of uniaxial cell-induced and externally applied tensile forces on the morphology of vascular networks formed within fibroblast and endothelial cell-embedded 3D polymeric constructs. Force intensity correlated with network quality, as verified by inhibition of force and of angiogenesis-related regulators. Tensile forces during vessel formation resulted in parallel vessel orientation under static stretching and diagonal orientation under cyclic stretching, supported by angiogenic factors secreted in response to each stretch protocol. Implantation of scaffolds bearing network orientations matching those of host abdominal muscle tissue improved graft integration and the mechanical properties of the implantation site, a critical factor in repair of defects in this area. This study demonstrates the regulatory role of forces in angiogenesis and their capacities in vessel structure manipulation, which can be exploited to improve scaffolds for tissue repair. PMID:26951667

  4. Abnormality detection in retinal images using ant colony optimization and artificial neural networks - biomed 2010.

    PubMed

    Kavitha, Ganesan; Ramakrishnan, Swaminathan

    2010-01-01

    Optic disc and retinal vasculature are important anatomical structures in the retina of the eye and any changes observed in these structures provide vital information on severity of various diseases. Digital retinal images are shown to provide a meaningful way of documenting and assessing some of the key elements inside the eye including the optic nerve and the tiny retinal blood vessels. In this work, an attempt has been made to detect and differentiate abnormalities of the retina using Digital image processing together with Optimization based segmentation and Artificial Neural Network methods. The retinal fundus images were recorded using standard protocols. Ant Colony Optimization is employed to extract the most significant objects namely the optic disc and blood vessel. The features related to these objects are obtained and corresponding indices are also derived. Further, these features are subjected to classification using Radial Basis Function Neural Networks and compared with conventional training algorithms. Results show that the Ant Colony Optimization is efficient in extracting useful information from retinal images. The features derived are effective for classification of normal and abnormal images using Radial basis function networks compared to other methods. As Optic disc and blood vessels are significant markers of abnormality in retinal images, the method proposed appears to be useful for mass screening. In this paper, the objectives of the study, methodology and significant observations are presented. PMID:20467104

  5. Abnormality detection in retinal images using ant colony optimization and artificial neural networks - biomed 2010.

    PubMed

    Kavitha, Ganesan; Ramakrishnan, Swaminathan

    2010-01-01

    Optic disc and retinal vasculature are important anatomical structures in the retina of the eye and any changes observed in these structures provide vital information on severity of various diseases. Digital retinal images are shown to provide a meaningful way of documenting and assessing some of the key elements inside the eye including the optic nerve and the tiny retinal blood vessels. In this work, an attempt has been made to detect and differentiate abnormalities of the retina using Digital image processing together with Optimization based segmentation and Artificial Neural Network methods. The retinal fundus images were recorded using standard protocols. Ant Colony Optimization is employed to extract the most significant objects namely the optic disc and blood vessel. The features related to these objects are obtained and corresponding indices are also derived. Further, these features are subjected to classification using Radial Basis Function Neural Networks and compared with conventional training algorithms. Results show that the Ant Colony Optimization is efficient in extracting useful information from retinal images. The features derived are effective for classification of normal and abnormal images using Radial basis function networks compared to other methods. As Optic disc and blood vessels are significant markers of abnormality in retinal images, the method proposed appears to be useful for mass screening. In this paper, the objectives of the study, methodology and significant observations are presented.

  6. Identification of Abnormal System Noise Temperature Patterns in Deep Space Network Antennas Using Neural Network Trained Fuzzy Logic

    NASA Technical Reports Server (NTRS)

    Lu, Thomas; Pham, Timothy; Liao, Jason

    2011-01-01

    This paper presents the development of a fuzzy logic function trained by an artificial neural network to classify the system noise temperature (SNT) of antennas in the NASA Deep Space Network (DSN). The SNT data were classified into normal, marginal, and abnormal classes. The irregular SNT pattern was further correlated with link margin and weather data. A reasonably good correlation is detected among high SNT, low link margin and the effect of bad weather; however we also saw some unexpected non-correlations which merit further study in the future.

  7. 3D microtumors in vitro supported by perfused vascular networks.

    PubMed

    Sobrino, Agua; Phan, Duc T T; Datta, Rupsa; Wang, Xiaolin; Hachey, Stephanie J; Romero-López, Mónica; Gratton, Enrico; Lee, Abraham P; George, Steven C; Hughes, Christopher C W

    2016-01-01

    There is a growing interest in developing microphysiological systems that can be used to model both normal and pathological human organs in vitro. This "organs-on-chips" approach aims to capture key structural and physiological characteristics of the target tissue. Here we describe in vitro vascularized microtumors (VMTs). This "tumor-on-a-chip" platform incorporates human tumor and stromal cells that grow in a 3D extracellular matrix and that depend for survival on nutrient delivery through living, perfused microvessels. Both colorectal and breast cancer cells grow vigorously in the platform and respond to standard-of-care therapies, showing reduced growth and/or regression. Vascular-targeting agents with different mechanisms of action can also be distinguished, and we find that drugs targeting only VEGFRs (Apatinib and Vandetanib) are not effective, whereas drugs that target VEGFRs, PDGFR and Tie2 (Linifanib and Cabozantinib) do regress the vasculature. Tumors in the VMT show strong metabolic heterogeneity when imaged using NADH Fluorescent Lifetime Imaging Microscopy and, compared to their surrounding stroma, many show a higher free/bound NADH ratio consistent with their known preference for aerobic glycolysis. The VMT platform provides a unique model for studying vascularized solid tumors in vitro. PMID:27549930

  8. 3D microtumors in vitro supported by perfused vascular networks

    PubMed Central

    Sobrino, Agua; Phan, Duc T. T.; Datta, Rupsa; Wang, Xiaolin; Hachey, Stephanie J.; Romero-López, Mónica; Gratton, Enrico; Lee, Abraham P.; George, Steven C.; Hughes, Christopher C. W.

    2016-01-01

    There is a growing interest in developing microphysiological systems that can be used to model both normal and pathological human organs in vitro. This “organs-on-chips” approach aims to capture key structural and physiological characteristics of the target tissue. Here we describe in vitro vascularized microtumors (VMTs). This “tumor-on-a-chip” platform incorporates human tumor and stromal cells that grow in a 3D extracellular matrix and that depend for survival on nutrient delivery through living, perfused microvessels. Both colorectal and breast cancer cells grow vigorously in the platform and respond to standard-of-care therapies, showing reduced growth and/or regression. Vascular-targeting agents with different mechanisms of action can also be distinguished, and we find that drugs targeting only VEGFRs (Apatinib and Vandetanib) are not effective, whereas drugs that target VEGFRs, PDGFR and Tie2 (Linifanib and Cabozantinib) do regress the vasculature. Tumors in the VMT show strong metabolic heterogeneity when imaged using NADH Fluorescent Lifetime Imaging Microscopy and, compared to their surrounding stroma, many show a higher free/bound NADH ratio consistent with their known preference for aerobic glycolysis. The VMT platform provides a unique model for studying vascularized solid tumors in vitro. PMID:27549930

  9. Common and distinct structural network abnormalities in major depressive disorder and borderline personality disorder.

    PubMed

    Depping, Malte S; Wolf, Nadine D; Vasic, Nenad; Sambataro, Fabio; Thomann, Philipp A; Wolf, R Christian

    2016-02-01

    Major depressive disorder (MDD) and borderline personality disorder (BPD) show substantial overlap in both affective symptom expression and in regional brain volume reduction. To address the specificity of structural brain change for the respective diagnostic category, we investigated structural networks in MDD and BPD to identify shared and distinct patterns of abnormal brain volume associated with these phenotypically related disorders. Using magnetic resonance imaging at 3 T, we studied 22 females with MDD, 17 females with BPD and without comorbid posttraumatic stress disorder, and 22 age-matched female healthy controls. We used “source-based morphometry” (SBM) to investigate naturally grouping patterns of gray matter volume variation (i.e. “structural networks”) and the magnitude of their expression between groups. SBM identified three distinct structural networks which showed a significant group effect (p b 0.05, FDR-corrected). A bilateral frontostriatal network showed reduced volume in MDD compared to both controls and BPD patients. A medial temporal/medial frontal network was found to be significantly reduced in BPD compared to both controls and MDD patients. Decreased cingulate and lateral prefrontal volume was found in both MDD and BPD when compared to healthy individuals. In MDD significant relationships were found between depressive symptoms and a cingulate/lateral prefrontal structural pattern. In contrast, overall BPD symptoms and impulsivity scores were significantly associated with medial temporal/medial frontal network volume. The data suggest both distinct and common patterns of abnormal brain volume in MDD and BPD. Alterations of distinct structural networks differentially modulate clinical symptom expression in these disorders.

  10. Abnormal structural connectivity in the brain networks of children with hydrocephalus.

    PubMed

    Yuan, Weihong; Holland, Scott K; Shimony, Joshua S; Altaye, Mekibib; Mangano, Francesco T; Limbrick, David D; Jones, Blaise V; Nash, Tiffany; Rajagopal, Akila; Simpson, Sarah; Ragan, Dustin; McKinstry, Robert C

    2015-01-01

    Increased intracranial pressure and ventriculomegaly in children with hydrocephalus are known to have adverse effects on white matter structure. This study seeks to investigate the impact of hydrocephalus on topological features of brain networks in children. The goal was to investigate structural network connectivity, at both global and regional levels, in the brains in children with hydrocephalus using graph theory analysis and diffusion tensor tractography. Three groups of children were included in the study (29 normally developing controls, 9 preoperative hydrocephalus patients, and 17 postoperative hydrocephalus patients). Graph theory analysis was applied to calculate the global network measures including small-worldness, normalized clustering coefficients, normalized characteristic path length, global efficiency, and modularity. Abnormalities in regional network parameters, including nodal degree, local efficiency, clustering coefficient, and betweenness centrality, were also compared between the two patients groups (separately) and the controls using two tailed t-test at significance level of p < 0.05 (corrected for multiple comparison). Children with hydrocephalus in both the preoperative and postoperative groups were found to have significantly lower small-worldness and lower normalized clustering coefficient than controls. Children with hydrocephalus in the postoperative group were also found to have significantly lower normalized characteristic path length and lower modularity. At regional level, significant group differences (or differences at trend level) in regional network measures were found between hydrocephalus patients and the controls in a series of brain regions including the medial occipital gyrus, medial frontal gyrus, thalamus, cingulate gyrus, lingual gyrus, rectal gyrus, caudate, cuneus, and insular. Our data showed that structural connectivity analysis using graph theory and diffusion tensor tractography is sensitive to detect

  11. Functional organization of the vascular network of Physarum polycephalum

    NASA Astrophysics Data System (ADS)

    Baumgarten, Werner; Hauser, Marcus J. B.

    2013-04-01

    The plasmodium of the slime mould Physarum polycephalum forms a transportation network of veins, in which protoplasm is transported due to peristaltic pumping. This network forms a planar, weighted, undirected graph that, for the first time, can be extracted automatically from photographs or movies. Thus, data from real transportation networks have now become available for the investigation of network properties. We determine the local drag of the vein segments and use these data to calculate the transport efficiency. We unravel which veins form the backbone of the transportation network by using a centrality measure from graph theory. The principal vein segments lie on relatively ample cycles of veins, and the most important segments are those that belong simultaneously to two of these principal cycles. Each principal cycle contains a series of smaller cycles of veins of lower transport efficiency, thus reflecting the hierarchical and self-similar structure of the transportation network. Finally, we calculate accessibility maps that show how easily different nodes of the network may be reached from a given reference node.

  12. Positron Emission Tomography Reveals Abnormal Topological Organization in Functional Brain Network in Diabetic Patients

    PubMed Central

    Qiu, Xiangzhe; Zhang, Yanjun; Feng, Hongbo; Jiang, Donglang

    2016-01-01

    Recent studies have demonstrated alterations in the topological organization of structural brain networks in diabetes mellitus (DM). However, the DM-related changes in the topological properties in functional brain networks are unexplored so far. We therefore used fluoro-D-glucose positron emission tomography (FDG-PET) data to construct functional brain networks of 73 DM patients and 91 sex- and age-matched normal controls (NCs), followed by a graph theoretical analysis. We found that both DM patients and NCs had a small-world topology in functional brain network. In comparison to the NC group, the DM group was found to have significantly lower small-world index, lower normalized clustering coefficients and higher normalized characteristic path length. Moreover, for diabetic patients, the nodal centrality was significantly reduced in the right rectus, the right cuneus, the left middle occipital gyrus, and the left postcentral gyrus, and it was significantly increased in the orbitofrontal region of the left middle frontal gyrus, the left olfactory region, and the right paracentral lobule. Our results demonstrated that the diabetic brain was associated with disrupted topological organization in the functional PET network, thus providing functional evidence for the abnormalities of brain networks in DM. PMID:27303259

  13. Positron Emission Tomography Reveals Abnormal Topological Organization in Functional Brain Network in Diabetic Patients.

    PubMed

    Qiu, Xiangzhe; Zhang, Yanjun; Feng, Hongbo; Jiang, Donglang

    2016-01-01

    Recent studies have demonstrated alterations in the topological organization of structural brain networks in diabetes mellitus (DM). However, the DM-related changes in the topological properties in functional brain networks are unexplored so far. We therefore used fluoro-D-glucose positron emission tomography (FDG-PET) data to construct functional brain networks of 73 DM patients and 91 sex- and age-matched normal controls (NCs), followed by a graph theoretical analysis. We found that both DM patients and NCs had a small-world topology in functional brain network. In comparison to the NC group, the DM group was found to have significantly lower small-world index, lower normalized clustering coefficients and higher normalized characteristic path length. Moreover, for diabetic patients, the nodal centrality was significantly reduced in the right rectus, the right cuneus, the left middle occipital gyrus, and the left postcentral gyrus, and it was significantly increased in the orbitofrontal region of the left middle frontal gyrus, the left olfactory region, and the right paracentral lobule. Our results demonstrated that the diabetic brain was associated with disrupted topological organization in the functional PET network, thus providing functional evidence for the abnormalities of brain networks in DM. PMID:27303259

  14. Abnormal Connectional Fingerprint in Schizophrenia: A Novel Network Analysis of Diffusion Tensor Imaging Data

    PubMed Central

    Edwin Thanarajah, Sharmili; Han, Cheol E.; Rotarska-Jagiela, Anna; Singer, Wolf; Deichmann, Ralf; Maurer, Konrad; Kaiser, Marcus; Uhlhaas, Peter J.

    2016-01-01

    The graph theoretical analysis of structural magnetic resonance imaging (MRI) data has received a great deal of interest in recent years to characterize the organizational principles of brain networks and their alterations in psychiatric disorders, such as schizophrenia. However, the characterization of networks in clinical populations can be challenging, since the comparison of connectivity between groups is influenced by several factors, such as the overall number of connections and the structural abnormalities of the seed regions. To overcome these limitations, the current study employed the whole-brain analysis of connectional fingerprints in diffusion tensor imaging data obtained at 3 T of chronic schizophrenia patients (n = 16) and healthy, age-matched control participants (n = 17). Probabilistic tractography was performed to quantify the connectivity of 110 brain areas. The connectional fingerprint of a brain area represents the set of relative connection probabilities to all its target areas and is, hence, less affected by overall white and gray matter changes than absolute connectivity measures. After detecting brain regions with abnormal connectional fingerprints through similarity measures, we tested each of its relative connection probability between groups. We found altered connectional fingerprints in schizophrenia patients consistent with a dysconnectivity syndrome. While the medial frontal gyrus showed only reduced connectivity, the connectional fingerprints of the inferior frontal gyrus and the putamen mainly contained relatively increased connection probabilities to areas in the frontal, limbic, and subcortical areas. These findings are in line with previous studies that reported abnormalities in striatal–frontal circuits in the pathophysiology of schizophrenia, highlighting the potential utility of connectional fingerprints for the analysis of anatomical networks in the disorder. PMID:27445870

  15. Abnormal Connectional Fingerprint in Schizophrenia: A Novel Network Analysis of Diffusion Tensor Imaging Data.

    PubMed

    Edwin Thanarajah, Sharmili; Han, Cheol E; Rotarska-Jagiela, Anna; Singer, Wolf; Deichmann, Ralf; Maurer, Konrad; Kaiser, Marcus; Uhlhaas, Peter J

    2016-01-01

    The graph theoretical analysis of structural magnetic resonance imaging (MRI) data has received a great deal of interest in recent years to characterize the organizational principles of brain networks and their alterations in psychiatric disorders, such as schizophrenia. However, the characterization of networks in clinical populations can be challenging, since the comparison of connectivity between groups is influenced by several factors, such as the overall number of connections and the structural abnormalities of the seed regions. To overcome these limitations, the current study employed the whole-brain analysis of connectional fingerprints in diffusion tensor imaging data obtained at 3 T of chronic schizophrenia patients (n = 16) and healthy, age-matched control participants (n = 17). Probabilistic tractography was performed to quantify the connectivity of 110 brain areas. The connectional fingerprint of a brain area represents the set of relative connection probabilities to all its target areas and is, hence, less affected by overall white and gray matter changes than absolute connectivity measures. After detecting brain regions with abnormal connectional fingerprints through similarity measures, we tested each of its relative connection probability between groups. We found altered connectional fingerprints in schizophrenia patients consistent with a dysconnectivity syndrome. While the medial frontal gyrus showed only reduced connectivity, the connectional fingerprints of the inferior frontal gyrus and the putamen mainly contained relatively increased connection probabilities to areas in the frontal, limbic, and subcortical areas. These findings are in line with previous studies that reported abnormalities in striatal-frontal circuits in the pathophysiology of schizophrenia, highlighting the potential utility of connectional fingerprints for the analysis of anatomical networks in the disorder.

  16. Abnormal Connectional Fingerprint in Schizophrenia: A Novel Network Analysis of Diffusion Tensor Imaging Data.

    PubMed

    Edwin Thanarajah, Sharmili; Han, Cheol E; Rotarska-Jagiela, Anna; Singer, Wolf; Deichmann, Ralf; Maurer, Konrad; Kaiser, Marcus; Uhlhaas, Peter J

    2016-01-01

    The graph theoretical analysis of structural magnetic resonance imaging (MRI) data has received a great deal of interest in recent years to characterize the organizational principles of brain networks and their alterations in psychiatric disorders, such as schizophrenia. However, the characterization of networks in clinical populations can be challenging, since the comparison of connectivity between groups is influenced by several factors, such as the overall number of connections and the structural abnormalities of the seed regions. To overcome these limitations, the current study employed the whole-brain analysis of connectional fingerprints in diffusion tensor imaging data obtained at 3 T of chronic schizophrenia patients (n = 16) and healthy, age-matched control participants (n = 17). Probabilistic tractography was performed to quantify the connectivity of 110 brain areas. The connectional fingerprint of a brain area represents the set of relative connection probabilities to all its target areas and is, hence, less affected by overall white and gray matter changes than absolute connectivity measures. After detecting brain regions with abnormal connectional fingerprints through similarity measures, we tested each of its relative connection probability between groups. We found altered connectional fingerprints in schizophrenia patients consistent with a dysconnectivity syndrome. While the medial frontal gyrus showed only reduced connectivity, the connectional fingerprints of the inferior frontal gyrus and the putamen mainly contained relatively increased connection probabilities to areas in the frontal, limbic, and subcortical areas. These findings are in line with previous studies that reported abnormalities in striatal-frontal circuits in the pathophysiology of schizophrenia, highlighting the potential utility of connectional fingerprints for the analysis of anatomical networks in the disorder. PMID:27445870

  17. Regulation of blood flow in the retinal trilaminar vascular network.

    PubMed

    Kornfield, Tess E; Newman, Eric A

    2014-08-20

    Light stimulation evokes neuronal activity in the retina, resulting in the dilation of retinal blood vessels and increased blood flow. This response, named functional hyperemia, brings oxygen and nutrients to active neurons. However, it remains unclear which vessels mediate functional hyperemia. We have characterized blood flow regulation in the rat retina in vivo by measuring changes in retinal vessel diameter and red blood cell (RBC) flux evoked by a flickering light stimulus. We found that, in first- and second-order arterioles, flicker evoked large (7.5 and 5.0%), rapid (0.73 and 0.70 s), and consistent dilations. Flicker-evoked dilations in capillaries were smaller (2.0%) and tended to have a slower onset (0.97 s), whereas dilations in venules were smaller (1.0%) and slower (1.06 s) still. The proximity of pericyte somata did not predict capillary dilation amplitude. Expression of the contractile protein α-smooth muscle actin was high in arterioles and low in capillaries. Unexpectedly, we found that blood flow in the three vascular layers was differentially regulated. Flicker stimulation evoked far larger dilations and RBC flux increases in the intermediate layer capillaries than in the superficial and deep layer capillaries (2.6 vs 0.9 and 0.7% dilation; 25.7 vs 0.8 and 11.3% RBC flux increase). These results indicate that functional hyperemia in the retina is driven primarily by active dilation of arterioles. The dilation of intermediate layer capillaries is likely mediated by active mechanisms as well. The physiological consequences of differential regulation in the three vascular layers are discussed.

  18. Regulation of Blood Flow in the Retinal Trilaminar Vascular Network

    PubMed Central

    Kornfield, Tess E.

    2014-01-01

    Light stimulation evokes neuronal activity in the retina, resulting in the dilation of retinal blood vessels and increased blood flow. This response, named functional hyperemia, brings oxygen and nutrients to active neurons. However, it remains unclear which vessels mediate functional hyperemia. We have characterized blood flow regulation in the rat retina in vivo by measuring changes in retinal vessel diameter and red blood cell (RBC) flux evoked by a flickering light stimulus. We found that, in first- and second-order arterioles, flicker evoked large (7.5 and 5.0%), rapid (0.73 and 0.70 s), and consistent dilations. Flicker-evoked dilations in capillaries were smaller (2.0%) and tended to have a slower onset (0.97 s), whereas dilations in venules were smaller (1.0%) and slower (1.06 s) still. The proximity of pericyte somata did not predict capillary dilation amplitude. Expression of the contractile protein α-smooth muscle actin was high in arterioles and low in capillaries. Unexpectedly, we found that blood flow in the three vascular layers was differentially regulated. Flicker stimulation evoked far larger dilations and RBC flux increases in the intermediate layer capillaries than in the superficial and deep layer capillaries (2.6 vs 0.9 and 0.7% dilation; 25.7 vs 0.8 and 11.3% RBC flux increase). These results indicate that functional hyperemia in the retina is driven primarily by active dilation of arterioles. The dilation of intermediate layer capillaries is likely mediated by active mechanisms as well. The physiological consequences of differential regulation in the three vascular layers are discussed. PMID:25143628

  19. Metabolic and vascular determinants of impaired cognitive performance and abnormalities on brain magnetic resonance imaging in patients with type 2 diabetes

    PubMed Central

    Biessels, G. J.; de Valk, H.; Algra, A.; Rutten, G. E. H. M.; van der Grond, J.; Kappelle, L. J.

    2007-01-01

    Aims/hypothesis The determinants of cerebral complications of type 2 diabetes are unclear. The present study aimed to identify metabolic and vascular factors that are associated with impaired cognitive performance and abnormalities on brain MRI in patients with type 2 diabetes. Methods The study included 122 patients and 56 controls. Neuropsychological test scores were divided into five cognitive domains and expressed as standardised z values. Brain MRI scans were rated for white matter lesions (WML), cortical and subcortical atrophy, and infarcts. Data on glucose metabolism, vascular risk factors and micro- and macrovascular disease were collected. Results Patients with type 2 diabetes had more cortical (p < 0.001) and subcortical (p < 0.01) atrophy and deep WML (p = 0.02) than the control group and their cognitive performance was worse. In multivariate regression analyses within the type 2 diabetes group, hypertension (p < 0.05) and a history of vascular events (p < 0.01) were associated with worse cognitive performance, while statin use was associated (p < 0.05) with better performance. Retinopathy and brain infarcts on MRI were associated with more severe cortical atrophy (both p < 0.01) and statin use with less atrophy (p < 0.05). Insulin level and brain infarcts were associated with more severe WML and statin use with less severe WML (all p < 0.05). Conclusions/interpretation Type 2 diabetes is associated with modest impairments in cognition, as well as atrophy and vascular lesions on MRI. This ‘diabetic encephalopathy’ is a multifactorial condition, for which atherosclerotic (macroangiopathic) vascular disease is an important determinant. Chronic hyperglycaemia, hyperinsulinaemia and hypertension may play additional roles. Electronic supplementary material The online version of this article (doi:10.1007/s00125-007-0792-z) contains details of the Utrecht Diabetic Encephalopathy Study Group, which are available to

  20. Evolution of the VEGF-regulated vascular network from a neural guidance system.

    PubMed

    Ponnambalam, Sreenivasan; Alberghina, Mario

    2011-06-01

    The vascular network is closely linked to the neural system, and an interdependence is displayed in healthy and in pathophysiological responses. How has close apposition of two such functionally different systems occurred? Here, we present a hypothesis for the evolution of the vascular network from an ancestral neural guidance system. Biological cornerstones of this hypothesis are the vascular endothelial growth factor (VEGF) protein family and cognate receptors. The primary sequences of such proteins are conserved from invertebrates, such as worms and flies that lack discernible vascular systems compared to mammals, but all these systems have sophisticated neuronal wiring involving such molecules. Ancestral VEGFs and receptors (VEGFRs) could have been used to develop and maintain the nervous system in primitive eukaryotes. During evolution, the demands of increased morphological complexity required systems for transporting molecules and cells, i.e., biological conductive tubes. We propose that the VEGF-VEGFR axis was subverted by evolution to mediate the formation of biological tubes necessary for transport of fluids, e.g., blood. Increasingly, there is evidence that aberrant VEGF-mediated responses are also linked to neuronal dysfunctions ranging from motor neuron disease, stroke, Parkinson's disease, Alzheimer's disease, ischemic brain disease, epilepsy, multiple sclerosis, and neuronal repair after injury, as well as common vascular diseases (e.g., retinal disease). Manipulation and correction of the VEGF response in different neural tissues could be an effective strategy to treat different neurological diseases.

  1. Tracing behavior of endothelial cells promotes vascular network formation.

    PubMed

    Yasuda, Noriko; Sekine, Hidekazu; Bise, Ryoma; Okano, Teruo; Shimizu, Tatsuya

    2016-05-01

    The in vitro formation of network structures derived from endothelial cells in grafts before transplantation contributes to earlier engraftment. In a previous study, endothelial cells migrated to form a net-shaped structure in co-culture. However, the specific network formation behavior of endothelial cells during migration remains unclear. In this study, we demonstrated the tracing behavior and cell cycle of endothelial cells using Fucci-labeled (Fluorescent Ubiquitination-based Cell Cycle Indicator) endothelial cells. Here, we observed the co-culture of Fucci-labeled human umbilical vein endothelial cells (HUVECs) together with normal human dermal fibroblasts (NHDFs) using time-lapse imaging and analyzed by multicellular concurrent tracking. In the G0/G1 period, HUVECs migrate faster than in the S/G2/M period, because G0/G1 is the mobile phase and S/G2/M is the proliferation phase in the cell cycle. When HUVECs are co-cultured, they tend to move randomly until they find existing tracks that they then follow to form clusters. Extracellular matrix (ECM) staining showed that collagen IV, laminin and thrombospondin deposited in accordance with endothelial cell networks. Therefore the HUVECs may migrate on the secreted ECM and exhibit tracing behavior, where the HUVECs migrate toward each other. These results suggested that ECM and a cell phase contributed to form a network by accelerating cell migration.

  2. A neural network learned information measures for heart motion abnormality detection

    NASA Astrophysics Data System (ADS)

    Nambakhsh, M. S.; Punithakumar, Kumaradevan; Ben Ayed, Ismail; Goela, Aashish; Islam, Ali; Peters, Terry; Li, Shuo

    2011-03-01

    In this study, we propose an information theoretic neural network for normal/abnormal left ventricular motion classification which outperforms significantly other recent methods in the literature. The proposed framework consists of a supervised 3-layer artificial neural network (ANN) which uses hyperbolic tangent sigmoid and linear transfer functions for hidden and output layers, respectively. The ANN is fed by information theoretic measures of left ventricular wall motion such as Shannon's differential entropy (SDE), Rényi entropy and Fisher information, which measure global information of subjects distribution. Using 395×20 segmented LV cavities of short-axis magnetic resonance images (MRI) acquired from 48 subjects, the experimental results show that the proposed method outperforms Support Vector Machine (SVM) and thresholding based information theoretic classifiers. It yields a specificity equal to 90%, a sensitivity of 91%, and a remarkable Area Under Curve (AUC) for Receiver Operating Characteristic (ROC), equal to 93.2%.

  3. Abnormal functional architecture of amygdala-centered networks in adolescent posttraumatic stress disorder.

    PubMed

    Aghajani, Moji; Veer, Ilya M; van Hoof, Marie-José; Rombouts, Serge A R B; van der Wee, Nic J; Vermeiren, Robert R J M

    2016-03-01

    Posttraumatic stress disorder (PTSD) is a prevalent, debilitating, and difficult to treat psychiatric disorder. Very little is known of how PTSD affects neuroplasticity in the developing adolescent brain. Whereas multiple lines of research implicate amygdala-centered network dysfunction in the pathophysiology of adult PTSD, no study has yet examined the functional architecture of amygdala subregional networks in adolescent PTSD. Using intrinsic functional connectivity analysis, we investigated functional connectivity of the basolateral (BLA) and centromedial (CMA) amygdala in 19 sexually abused adolescents with PTSD relative to 23 matched controls. Additionally, we examined whether altered amygdala subregional connectivity coincides with abnormal grey matter volume of the amygdaloid complex. Our analysis revealed abnormal amygdalar connectivity and morphology in adolescent PTSD patients. More specifically, PTSD patients showed diminished right BLA connectivity with a cluster including dorsal and ventral portions of the anterior cingulate and medial prefrontal cortices (p < 0.05, corrected). In contrast, PTSD patients showed increased left CMA connectivity with a cluster including the orbitofrontal and subcallosal cortices (p < 0.05, corrected). Critically, these connectivity changes coincided with diminished grey matter volume within BLA and CMA subnuclei (p < 0.05, corrected), with CMA connectivity shifts additionally relating to more severe symptoms of PTSD. These findings provide unique insights into how perturbations in major amygdalar circuits could hamper fear regulation and drive excessive acquisition and expression of fear in PTSD. As such, they represent an important step toward characterizing the neurocircuitry of adolescent PTSD, thereby informing the development of reliable biomarkers and potential therapeutic targets.

  4. Abnormal Ventral and Dorsal Attention Network Activity during Single and Dual Target Detection in Schizophrenia

    PubMed Central

    Jimenez, Amy M.; Lee, Junghee; Wynn, Jonathan K.; Cohen, Mark S.; Engel, Stephen A.; Glahn, David C.; Nuechterlein, Keith H.; Reavis, Eric A.; Green, Michael F.

    2016-01-01

    Early visual perception and attention are impaired in schizophrenia, and these deficits can be observed on target detection tasks. These tasks activate distinct ventral and dorsal brain networks which support stimulus-driven and goal-directed attention, respectively. We used single and dual target rapid serial visual presentation (RSVP) tasks during fMRI with an ROI approach to examine regions within these networks associated with target detection and the attentional blink (AB) in 21 schizophrenia outpatients and 25 healthy controls. In both tasks, letters were targets and numbers were distractors. For the dual target task, the second target (T2) was presented at three different lags after the first target (T1) (lag1 = 100 ms, lag3 = 300 ms, lag7 = 700ms). For both single and dual target tasks, patients identified fewer targets than controls. For the dual target task, both groups showed the expected AB effect with poorer performance at lag 3 than at lags 1 or 7, and there was no group by lag interaction. During the single target task, patients showed abnormally increased deactivation of the temporo-parietal junction (TPJ), a key region of the ventral network. When attention demands were increased during the dual target task, patients showed overactivation of the posterior intraparietal cortex, a key dorsal network region, along with failure to deactivate TPJ. Results suggest inefficient and faulty suppression of salience-oriented processing regions, resulting in increased sensitivity to stimuli in general, and difficulty distinguishing targets from non-targets. PMID:27014135

  5. Abnormalities of functional brain networks in pathological gambling: a graph-theoretical approach

    PubMed Central

    Tschernegg, Melanie; Crone, Julia S.; Eigenberger, Tina; Schwartenbeck, Philipp; Fauth-Bühler, Mira; Lemènager, Tagrid; Mann, Karl; Thon, Natasha; Wurst, Friedrich M.; Kronbichler, Martin

    2013-01-01

    Functional neuroimaging studies of pathological gambling (PG) demonstrate alterations in frontal and subcortical regions of the mesolimbic reward system. However, most investigations were performed using tasks involving reward processing or executive functions. Little is known about brain network abnormalities during task-free resting state in PG. In the present study, graph-theoretical methods were used to investigate network properties of resting state functional magnetic resonance imaging data in PG. We compared 19 patients with PG to 19 healthy controls (HCs) using the Graph Analysis Toolbox (GAT). None of the examined global metrics differed between groups. At the nodal level, pathological gambler showed a reduced clustering coefficient in the left paracingulate cortex and the left juxtapositional lobe (supplementary motor area, SMA), reduced local efficiency in the left SMA, as well as an increased node betweenness for the left and right paracingulate cortex and the left SMA. At an uncorrected threshold level, the node betweenness in the left inferior frontal gyrus was decreased and increased in the caudate. Additionally, increased functional connectivity between fronto-striatal regions and within frontal regions has also been found for the gambling patients. These findings suggest that regions associated with the reward system demonstrate reduced segregation but enhanced integration while regions associated with executive functions demonstrate reduced integration. The present study makes evident that PG is also associated with abnormalities in the topological network structure of the brain during rest. Since alterations in PG cannot be explained by direct effects of abused substances on the brain, these findings will be of relevance for understanding functional connectivity in other addictive disorders. PMID:24098282

  6. The Effects of Antidepressants “Fluoxetine and Imipramine” on Vascular Abnormalities and Toll Like Receptor-4 Expression in Diabetic and Non-Diabetic Rats Exposed to Chronic Stress

    PubMed Central

    Habib, Mohamed; Shaker, Safaa; El-Gayar, Nesreen; Aboul-Fotouh, Sawsan

    2015-01-01

    Several studies reveal that diabetes doubles the odds of comorbid depression with evidence of a pro-inflammatory state underlying its vascular complications. Indeed, little information is available about vascular effects of antidepressant drugs in diabetes. Method: We investigated the effect of chronic administration of fluoxetine “FLU” and imipramine “IMIP” on behavioral, metabolic and vascular abnormalities in diabetic and non-diabetic rats exposed to chronic restraint stress (CRS). Results: Both diabetes and CRS induced depressive-like behavior which was more prominent in diabetic/depressed rats; this was reversed by chronic treatment with FLU and IMIP in a comparable manner. Diabetic and non-diabetic rats exposed to CRS exhibited abnormalities in glucose homeostasis, lipid profile and vascular function, manifested by decreased endothelium-dependent relaxation, increased systolic blood pressure and histopathological atherosclerotic changes. Vascular and metabolic dysfunctions were associated with significant increase in aortic expression of TLR-4, and pro-inflammatory cytokines (TNF-α and IL-1ß). FLU ameliorated these metabolic, vascular and inflammatory abnormalities, while IMIP induced either no change or even worsening of some parameters. Conclusion: FLU has favorable effect over IMIP on metabolic, vascular and inflammatory aberrations associated with DM and CRS in Wistar rats, clarifying the preference of FLU over IMIP in management of comorbid depression in diabetic subjects. PMID:25826421

  7. Abnormal topological organization of the white matter network in Mandarin speakers with congenital amusia.

    PubMed

    Zhao, Yanxin; Chen, Xizhuo; Zhong, Suyu; Cui, Zaixu; Gong, Gaolang; Dong, Qi; Nan, Yun

    2016-01-01

    Congenital amusia is a neurogenetic disorder that mainly affects the processing of musical pitch. Brain imaging evidence indicates that it is associated with abnormal structural and functional connections in the fronto-temporal region. However, a holistic understanding of the anatomical topology underlying amusia is still lacking. Here, we used probabilistic diffusion tensor imaging tractography and graph theory to examine whole brain white matter structural connectivity in 31 Mandarin-speaking amusics and 24 age- and IQ-matched controls. Amusics showed significantly reduced global connectivity, as indicated by the abnormally decreased clustering coefficient (Cp) and increased normalized shortest path length (λ) compared to the controls. Moreover, amusics exhibited enhanced nodal strength in the right inferior parietal lobule relative to controls. The co-existence of the lexical tone deficits was associated with even more deteriorated global network efficiency in amusics, as suggested by the significant correlation between the increments in normalized shortest path length (λ) and the insensitivity in lexical tone perception. Our study is the first to reveal reduced global connectivity efficiency in amusics as well as an increase in the global connectivity cost due to the co-existed lexical tone deficits. Taken together these results provide a holistic perspective on the anatomical substrates underlying congenital amusia. PMID:27211239

  8. Abnormal topological organization of the white matter network in Mandarin speakers with congenital amusia

    PubMed Central

    Zhao, Yanxin; Chen, Xizhuo; Zhong, Suyu; Cui, Zaixu; Gong, Gaolang; Dong, Qi; Nan, Yun

    2016-01-01

    Congenital amusia is a neurogenetic disorder that mainly affects the processing of musical pitch. Brain imaging evidence indicates that it is associated with abnormal structural and functional connections in the fronto-temporal region. However, a holistic understanding of the anatomical topology underlying amusia is still lacking. Here, we used probabilistic diffusion tensor imaging tractography and graph theory to examine whole brain white matter structural connectivity in 31 Mandarin-speaking amusics and 24 age- and IQ-matched controls. Amusics showed significantly reduced global connectivity, as indicated by the abnormally decreased clustering coefficient (Cp) and increased normalized shortest path length (λ) compared to the controls. Moreover, amusics exhibited enhanced nodal strength in the right inferior parietal lobule relative to controls. The co-existence of the lexical tone deficits was associated with even more deteriorated global network efficiency in amusics, as suggested by the significant correlation between the increments in normalized shortest path length (λ) and the insensitivity in lexical tone perception. Our study is the first to reveal reduced global connectivity efficiency in amusics as well as an increase in the global connectivity cost due to the co-existed lexical tone deficits. Taken together these results provide a holistic perspective on the anatomical substrates underlying congenital amusia. PMID:27211239

  9. Testing Foundations of Biological Scaling Theory Using Automated Measurements of Vascular Networks

    PubMed Central

    Newberry, Mitchell G; Ennis, Daniel B; Savage, Van M

    2015-01-01

    Scientists have long sought to understand how vascular networks supply blood and oxygen to cells throughout the body. Recent work focuses on principles that constrain how vessel size changes through branching generations from the aorta to capillaries and uses scaling exponents to quantify these changes. Prominent scaling theories predict that combinations of these exponents explain how metabolic, growth, and other biological rates vary with body size. Nevertheless, direct measurements of individual vessel segments have been limited because existing techniques for measuring vasculature are invasive, time consuming, and technically difficult. We developed software that extracts the length, radius, and connectivity of in vivo vessels from contrast-enhanced 3D Magnetic Resonance Angiography. Using data from 20 human subjects, we calculated scaling exponents by four methods—two derived from local properties of branching junctions and two from whole-network properties. Although these methods are often used interchangeably in the literature, we do not find general agreement between these methods, particularly for vessel lengths. Measurements for length of vessels also diverge from theoretical values, but those for radius show stronger agreement. Our results demonstrate that vascular network models cannot ignore certain complexities of real vascular systems and indicate the need to discover new principles regarding vessel lengths. PMID:26317654

  10. Peanut witches' broom (PnWB) phytoplasma-mediated leafy flower symptoms and abnormal vascular bundles development.

    PubMed

    Liu, Chi-Te; Huang, Hsin-Mei; Hong, Syuan-Fei; Kuo-Huang, Ling-Long; Yang, Chiao-Yin; Lin, Yen-Yu; Lin, Chan-Pin; Lin, Shih-Shun

    2015-01-01

    The peanut witches' broom (PnWB) phytoplasma causes virescence symptoms such as phyllody (leafy flower) in infected peanuts. However, the obligate nature of phytoplasma limits the study of host-pathogen interactions, and the detailed anatomy of PnWB-infected plants has yet to be reported. Here, we demonstrate that 4',6'-diamidino-2-phenylindole (DAPI) staining can be used to track PnWB infection. The DAPI-stained phytoplasma cells were observed in phloem/internal phloem tissues, and changes in vascular bundle morphology, including increasing pith rays and thinner cell walls in the xylem, were found. We also discerned the cell types comprising PnWB in infected sieve tube members. These results suggest that the presence of PnWB in phloem tissue facilitates the transmission of phytoplasma via sap-feeding insect vectors. In addition, PnWB in sieve tube members and changes in vascular bundle morphology might strongly promote the ability of phytoplasmas to assimilate nutrients. These data will help further an understanding of the obligate life cycle and host-pathogen interactions of phytoplasma.

  11. Peanut witches' broom (PnWB) phytoplasma-mediated leafy flower symptoms and abnormal vascular bundles development

    PubMed Central

    Liu, Chi-Te; Huang, Hsin-Mei; Hong, Syuan-Fei; Kuo-Huang, Ling-Long; Yang, Chiao-Yin; Lin, Yen-Yu; Lin, Chan-Pin; Lin, Shih-Shun

    2015-01-01

    The peanut witches' broom (PnWB) phytoplasma causes virescence symptoms such as phyllody (leafy flower) in infected peanuts. However, the obligate nature of phytoplasma limits the study of host-pathogen interactions, and the detailed anatomy of PnWB-infected plants has yet to be reported. Here, we demonstrate that 4′,6′-diamidino-2-phenylindole (DAPI) staining can be used to track PnWB infection. The DAPI-stained phytoplasma cells were observed in phloem/internal phloem tissues, and changes in vascular bundle morphology, including increasing pith rays and thinner cell walls in the xylem, were found. We also discerned the cell types comprising PnWB in infected sieve tube members. These results suggest that the presence of PnWB in phloem tissue facilitates the transmission of phytoplasma via sap-feeding insect vectors. In addition, PnWB in sieve tube members and changes in vascular bundle morphology might strongly promote the ability of phytoplasmas to assimilate nutrients. These data will help further an understanding of the obligate life cycle and host-pathogen interactions of phytoplasma. PMID:26492318

  12. Identification of inter-organ vascular network: vessels bridging between organs.

    PubMed

    Omae, Madoka; Takada, Norio; Yamamoto, Shohei; Nakajima, Hiroyuki; Sato, Thomas N

    2013-01-01

    Development and homeostasis of organs and whole body is critically dependent on the circulatory system. In particular, the circulatory system, the railways shuttling oxygen and nutrients among various organs, is indispensible for inter-organ humoral communication. Since the modern view of the anatomy and mechanics of the circulatory system was established in 17(th) century, it has been assumed that humoral factors are carried to and from organs via vascular branches of the central arteries and veins running along the body axis. Over the past few decades, major advances have been made in understanding molecular and cellular mechanisms underlying the vascularization of organs. However, very little is known about how each organ is linked by vasculature (i.e., inter-organ vascular networks). In fact, the exact anatomy of inter-organ vascular networks has remained obscure. Herein, we report the identification of four distinct vessels, V1(LP), V2(LP), V3(LP) and V4(LP), that bridge between two organs, liver and pancreas in developing zebrafish. We found that these inter-organ vessels can be classified into two types: direct and indirect types. The direct type vessels are those that bridge between two organs via single distinct vessel, to which V1(LP) and V2(LP) vessels belong. The indirect type bridges between two organs via separate branches that emanate from a stem vessel, and V3(LP) and V4(LP) vessels belong to this type. Our finding of V1(LP), V2(LP), V3(LP) and V4(LP) vessels provides the proof of the existence of inter-organ vascular networks. These and other yet-to-be-discovered inter-organ vascular networks may facilitate the direct exchange of humoral factors that are necessary for the coordinated growth, differentiation and homeostasis of the connected organs. It is also possible that the inter-organ vessels serve as tracks for their connected organs to follow during their growth to establish their relative positions and size differences.

  13. Long-lasting intestinal bleeding in an old patient with multiple mucosal vascular abnormalities and Glanzmann's thrombasthenia: 3-year pharmacological management.

    PubMed

    Coppola, A; De Stefano, V; Tufano, A; Nardone, G; Amoriello, A; Cerbone, A M; Di Minno, G

    2002-09-01

    A 75-year-old woman with Glanzmann's thrombasthenia was admitted because of persistent melaena. Endoscopic examination showed multiple angiodysplastic lesions, with active bleeding in small and large bowel. Electro-coagulation of some lesions, octreotide, conjugated oestrogens and selective embolization of jejunal vessels did not change transfusion requirements. After 8 month-transfusions, ethinylestradiol + norethisterone in association with octreotide was started, leading to no transfusion over the following 9 months. Bleeding recurred after withdrawing octreotide and substituting ethinylestradiol + norgestrel for the ethinylestradiol + norethisterone combination. Re-introduction of octreotide did not improve bleeding; however, a reduction of transfusion requirement was observed when the ethinylestradiol + norethisterone pill was re-administered. The association of octreotide and of an oestrogen-progesterone combination was helpful in the difficult management of recurrent bleeding in this patient with diffuse gastrointestinal vascular abnormalities and a severe condition predisposing to bleeding. PMID:12270009

  14. Long-lasting intestinal bleeding in an old patient with multiple mucosal vascular abnormalities and Glanzmann's thrombasthenia: 3-year pharmacological management.

    PubMed

    Coppola, A; De Stefano, V; Tufano, A; Nardone, G; Amoriello, A; Cerbone, A M; Di Minno, G

    2002-09-01

    A 75-year-old woman with Glanzmann's thrombasthenia was admitted because of persistent melaena. Endoscopic examination showed multiple angiodysplastic lesions, with active bleeding in small and large bowel. Electro-coagulation of some lesions, octreotide, conjugated oestrogens and selective embolization of jejunal vessels did not change transfusion requirements. After 8 month-transfusions, ethinylestradiol + norethisterone in association with octreotide was started, leading to no transfusion over the following 9 months. Bleeding recurred after withdrawing octreotide and substituting ethinylestradiol + norgestrel for the ethinylestradiol + norethisterone combination. Re-introduction of octreotide did not improve bleeding; however, a reduction of transfusion requirement was observed when the ethinylestradiol + norethisterone pill was re-administered. The association of octreotide and of an oestrogen-progesterone combination was helpful in the difficult management of recurrent bleeding in this patient with diffuse gastrointestinal vascular abnormalities and a severe condition predisposing to bleeding.

  15. Wholemount imaging reveals abnormalities of the aqueous outflow pathway and corneal vascularity in Foxc1 and Bmp4 heterozygous mice.

    PubMed

    van der Merwe, Elizabeth L; Kidson, Susan H

    2016-05-01

    Mutations in the FOXC1/Foxc1 gene in humans and mice and Bmp4 in mice are associated with congenital anterior segment dysgenesis (ASD) and the development of the aqueous outflow structures throughout the limbus. The aim of this study was to advance our understanding of anterior segment abnormalities in mouse models of ASD using a 3-D imaging approach. Holistic imaging information combined with quantitative measurements were carried out on PECAM-1 stained individual components of the aqueous outflow vessels and corneal vasculature of Foxc1(+/-) on the C57BL/6Jx129 and ICR backgrounds, Bmp4(+/-) ICR mice, and wildtype mice from each background. In both wildtype and heterozygotes, singular, bifurcated and plexus forms of Schlemm's canal were noted. Of note, missing portions of the canal were seen in the heterozygous groups but not in wildtype animals. In general, we found the number of collector channels to be reduced in both heterozygotes. Lastly, we found a significant increase in the complexity of the corneal arcades and their penetration into the cornea in heterozygotes as compared with wild types. In conclusion, our 3-D imaging studies have revealed a more complex arrangement of both the aqueous vessels and corneal arcades in Foxc1(+/-) and Bmp4(+/-) heterozygotes, and further advance our understanding of how such abnormalities could impact on IOP and the aetiology of glaucoma.

  16. Wholemount imaging reveals abnormalities of the aqueous outflow pathway and corneal vascularity in Foxc1 and Bmp4 heterozygous mice.

    PubMed

    van der Merwe, Elizabeth L; Kidson, Susan H

    2016-05-01

    Mutations in the FOXC1/Foxc1 gene in humans and mice and Bmp4 in mice are associated with congenital anterior segment dysgenesis (ASD) and the development of the aqueous outflow structures throughout the limbus. The aim of this study was to advance our understanding of anterior segment abnormalities in mouse models of ASD using a 3-D imaging approach. Holistic imaging information combined with quantitative measurements were carried out on PECAM-1 stained individual components of the aqueous outflow vessels and corneal vasculature of Foxc1(+/-) on the C57BL/6Jx129 and ICR backgrounds, Bmp4(+/-) ICR mice, and wildtype mice from each background. In both wildtype and heterozygotes, singular, bifurcated and plexus forms of Schlemm's canal were noted. Of note, missing portions of the canal were seen in the heterozygous groups but not in wildtype animals. In general, we found the number of collector channels to be reduced in both heterozygotes. Lastly, we found a significant increase in the complexity of the corneal arcades and their penetration into the cornea in heterozygotes as compared with wild types. In conclusion, our 3-D imaging studies have revealed a more complex arrangement of both the aqueous vessels and corneal arcades in Foxc1(+/-) and Bmp4(+/-) heterozygotes, and further advance our understanding of how such abnormalities could impact on IOP and the aetiology of glaucoma. PMID:27068508

  17. Abnormal peripheral circulation in type 2 diabetic patients with normal ankle-brachial index associates with coronary atherosclerosis, large artery stiffness, and peripheral vascular resistance.

    PubMed

    Tsuchiya, Masanobu; Suzuki, Eiji; Egawa, Katsuya; Nishio, Yoshihiko; Maegawa, Hiroshi; Morikawa, Shigehiro; Inubushi, Toshiro; Kashiwagi, Atsunori

    2005-12-01

    We tested the hypothesis that impaired peripheral circulation in diabetes arises from different aspects of vascular abnormalities even when accompanied by a normal ankle-brachial index (ABI>0.9). One hundred fourteen type 2 diabetic patients with normal ABI and 33 age-matched non-diabetic subjects consecutively admitted to our hospital were enrolled. The Agatston coronary artery calcium score (CACS), as a marker of coronary atherosclerosis, was obtained using electron-beam computed tomography. An automatic device was used to measure brachial-ankle pulse wave velocity (baPWV) as an index of arterial distensibility. Total flow volume and resistive index (RI), as a marker of peripheral vascular resistance, at the popliteal artery were evaluated using gated two-dimensional cine-mode phase-contrast magnetic resonance imaging. Diabetic patients had baPWV (P<0.001) and RI (P<0.001) higher than those in the non-diabetic subjects, indicating that those parameters are characteristically altered in diabetic patients. When diabetic patients were grouped into three subgroups according to their levels of total flow volume, those with the lowest range showed the highest log-transformed CACS (P<0.001), baPWV (P<0.001), and RI (P<0.001) among the groups. Total flow volume was negatively correlated with log-transformed CACS (P<0.001), baPWV (P<0.001), and RI (P<0.001). Waveform at the popliteal artery could be clearly separated into systolic and early and late diastolic blood flows, which were negatively correlated with log-transformed CACS (P<0.001), RI (P<0.001), and baPWV (P<0.001), respectively. These results suggest that impaired peripheral circulation in diabetes is attributable to coronary atherosclerosis, large artery stiffness, and peripheral vascular resistance even when ABI is normal.

  18. Generation of Multi-Scale Vascular Network System within 3D Hydrogel using 3D Bio-Printing Technology.

    PubMed

    Lee, Vivian K; Lanzi, Alison M; Haygan, Ngo; Yoo, Seung-Schik; Vincent, Peter A; Dai, Guohao

    2014-09-01

    Although 3D bio-printing technology has great potential in creating complex tissues with multiple cell types and matrices, maintaining the viability of thick tissue construct for tissue growth and maturation after the printing is challenging due to lack of vascular perfusion. Perfused capillary network can be a solution for this issue; however, construction of a complete capillary network at single cell level using the existing technology is nearly impossible due to limitations in time and spatial resolution of the dispensing technology. To address the vascularization issue, we developed a 3D printing method to construct larger (lumen size of ~1mm) fluidic vascular channels and to create adjacent capillary network through a natural maturation process, thus providing a feasible solution to connect the capillary network to the large perfused vascular channels. In our model, microvascular bed was formed in between two large fluidic vessels, and then connected to the vessels by angiogenic sprouting from the large channel edge. Our bio-printing technology has a great potential in engineering vascularized thick tissues and vascular niches, as the vascular channels are simultaneously created while cells and matrices are printed around the channels in desired 3D patterns. PMID:25484989

  19. Generation of Multi-Scale Vascular Network System within 3D Hydrogel using 3D Bio-Printing Technology.

    PubMed

    Lee, Vivian K; Lanzi, Alison M; Haygan, Ngo; Yoo, Seung-Schik; Vincent, Peter A; Dai, Guohao

    2014-09-01

    Although 3D bio-printing technology has great potential in creating complex tissues with multiple cell types and matrices, maintaining the viability of thick tissue construct for tissue growth and maturation after the printing is challenging due to lack of vascular perfusion. Perfused capillary network can be a solution for this issue; however, construction of a complete capillary network at single cell level using the existing technology is nearly impossible due to limitations in time and spatial resolution of the dispensing technology. To address the vascularization issue, we developed a 3D printing method to construct larger (lumen size of ~1mm) fluidic vascular channels and to create adjacent capillary network through a natural maturation process, thus providing a feasible solution to connect the capillary network to the large perfused vascular channels. In our model, microvascular bed was formed in between two large fluidic vessels, and then connected to the vessels by angiogenic sprouting from the large channel edge. Our bio-printing technology has a great potential in engineering vascularized thick tissues and vascular niches, as the vascular channels are simultaneously created while cells and matrices are printed around the channels in desired 3D patterns.

  20. Generation of Multi-Scale Vascular Network System within 3D Hydrogel using 3D Bio-Printing Technology

    PubMed Central

    Lee, Vivian K.; Lanzi, Alison M.; Haygan, Ngo; Yoo, Seung-Schik; Vincent, Peter A.; Dai, Guohao

    2014-01-01

    Although 3D bio-printing technology has great potential in creating complex tissues with multiple cell types and matrices, maintaining the viability of thick tissue construct for tissue growth and maturation after the printing is challenging due to lack of vascular perfusion. Perfused capillary network can be a solution for this issue; however, construction of a complete capillary network at single cell level using the existing technology is nearly impossible due to limitations in time and spatial resolution of the dispensing technology. To address the vascularization issue, we developed a 3D printing method to construct larger (lumen size of ~1mm) fluidic vascular channels and to create adjacent capillary network through a natural maturation process, thus providing a feasible solution to connect the capillary network to the large perfused vascular channels. In our model, microvascular bed was formed in between two large fluidic vessels, and then connected to the vessels by angiogenic sprouting from the large channel edge. Our bio-printing technology has a great potential in engineering vascularized thick tissues and vascular niches, as the vascular channels are simultaneously created while cells and matrices are printed around the channels in desired 3D patterns. PMID:25484989

  1. [Morphological changes of vascular network of the midpalatal suture and palate mucosa after rapid maxillary expansion].

    PubMed

    Hirose, T

    1989-01-01

    Rapid maxillary expansion has been utilized for years in the treatment of transverse maxillomandibular discrepancies. It is important to understand the changes of the vascular network in midpalatal suture following rapid maxillary expansion. The reason is because it is critical to maintain the blood supply and circulation for the osteogenesis and bone remodeling after the expansion. The purpose of this study was to examine the morphological changes in the vascular network of the palate regions following rapid maxillary expansion. A total of 30 dogs were divided into 6 groups of 5 dogs each, of which one group was used as a control. A skeleton type rapid maxillary expansion appliance was utilized in the 5 experimental groups. Transverse expansion was accomplished by activating the appliances 0.4 mm each day for 10 days, achieving a total of 4.0 mm of width increase. The animals were sacrificed and injected with acrylic resin through the maxillary artery at 3, 7, 14, 21 and 28 days. The thin sections were examined with a light microscope and fine vascular corrosion specimens were examined with a scanning electron microscope. The results were as follows: 1. Vascular network in the midpalatal suture. 1) The suture appeared as an interdigitating bony processes separated by a relatively narrow gap. The blood vessels were running in the direction from the posterior to anterior in the control. 2) 3 days after the expansion, the suture had separated. The hemorrhage which accompanied the expansion was not observed, though hyperemia and enlargement of the blood vessels were observed. The stretched blood vessels from the bone walls observed along the stretched fiber bundles were remarkable. A few new blood vessels were observed in various places in the bone walls. 3) 7 and 14 days after the expansion, the number of new blood vessels increased significantly and anastomosed. The tube-shaped new bone formation was observed in parts of the bone walls along the stretched fiber

  2. Abnormal activation of the motor cortical network in idiopathic scoliosis demonstrated by functional MRI.

    PubMed

    Domenech, Julio; García-Martí, G; Martí-Bonmatí, L; Barrios, C; Tormos, J M; Pascual-Leone, A

    2011-07-01

    The aetiology of idiopathic scoliosis (IS) remains unknown, but there is growing support for the possibility of an underlying neurological disorder. Functional magnetic resonance imaging (fMRI) can characterize the abnormal activation of the sensorimotor brain network in movement disorders and could provide further insights into the neuropathogenesis of IS. Twenty subjects were included in the study; 10 adolescents with IS (mean age of 15.2, 8 girls and 2 boys) and 10 age-matched healthy controls. The average Cobb angle of the primary curve in the IS patients was 35° (range 27°-55°). All participants underwent a block-design fMRI experiment in a 1.5-Tesla MRI scanner to explore cortical activation following a simple motor task. Rest periods alternated with activation periods during which participants were required to open and close their hand at an internally paced rate of approximately 1 Hz. Data were analyzed with Statistical Parametric Mapping (SPM5) including age, sex and laterality as nuisance variables to minimise the presence of bias in the results. Compared to controls, IS patients showed significant increases in blood oxygenation level dependent (BOLD) activity in contralateral supplementary motor area when performing the motor task with either hand. No significant differences were observed when testing between groups in the functional activation in the primary motor cortex, premotor cortex and somatosensory cortex. Additionally, the IS group showed a greater interhemispheric asymmetry index than the control group (0.30 vs. 0.13, p < 0.001). This study demonstrates an abnormal pattern of brain activation in secondary motor areas during movement execution in patients with IS. These findings support the hypothesis that a sensorimotor integration disorder underlies the pathogenesis of IS.

  3. Control of vascular network location in millimeter-sized 3D-tissues by micrometer-sized collagen coated cells.

    PubMed

    Liu, Chun-Yen; Matsusaki, Michiya; Akashi, Mitsuru

    2016-03-25

    Engineering three-dimensional (3D) vascularized constructs remains a central challenge because capillary network structures are important for sufficient oxygen and nutrient exchange to sustain the viability of engineered constructs. However, construction of 3D-tissues at single cell level has yet to be reported. Previously, we established a collagen coating method for fabricating a micrometer-sized collagen matrix on cell surfaces to control cell distance or cell densities inside tissues. In this study, a simple fabrication method is presented for constructing vascular networks in 3D-tissues over micrometer-sized or even millimeter-sized with controlled cell densities. From the results, well vascularized 3D network structures can be observed with a fluorescence label method mixing collagen coated cells and endothelia cells, indicating that constructed ECM rich tissues have the potential for vascularization, which opens up the possibility for various applications in pharmaceutical or tissue engineering fields.

  4. Oxygen Advection and Diffusion in a Three Dimensional Vascular Anatomical Network

    PubMed Central

    Fang, Qianqian; Sakadžić, Sava; Ruvinskaya, Lana; Devor, Anna; Dale, Anders M.; Boas, David A.

    2008-01-01

    There is an increasing need for quantitative and computationally affordable models for analyzing tissue metabolism and hemodynamics in microvascular networks. In this work, we develop a hybrid model to solve for the time-varying oxygen advection-diffusion equation in the vessels and tissue. To obtain a three-dimensional temporal evolution of tissue oxygen concentration for realistic complex vessel networks, we used a graph-based advection model combined with a finite-element based diffusion model and an implicit time-advancing scheme. We validated this algorithm for both static and dynamic conditions. We also applied it to a complex vascular network obtained from a rodent somatosensory cortex. Qualitative agreement was found with in-vivo experiments. PMID:18958033

  5. Preferential Effect of Synchrotron Microbeam Radiation Therapy on Intracerebral 9L Gliosarcoma Vascular Networks

    SciTech Connect

    Bouchet, Audrey; Lemasson, Benjamin; Le Duc, Geraldine; Maisin, Cecile; Braeuer-Krisch, Elke; Siegbahn, Erik Albert; Renaud, Luc; Khalil, Enam; Remy, Chantal; Poillot, Cathy; Bravin, Alberto; Laissue, Jean A.; Barbier, Emmanuel L.; Serduc, Raphael

    2010-12-01

    Purpose: Synchrotron microbeam radiation therapy (MRT) relies on spatial fractionation of the incident photon beam into parallel micron-wide beams. Our aim was to analyze the effects of MRT on normal brain and 9L gliosarcoma tissues, particularly on blood vessels. Methods and Materials: Responses to MRT (two arrays, one lateral, one anteroposterior (2 x 400 Gy), intersecting orthogonally in the tumor region) were studied during 6 weeks using MRI, immunohistochemistry, and vascular endothelial growth factor Western blot. Results: MRT increased the median survival time of irradiated rats (x3.25), significantly increased blood vessel permeability, and inhibited tumor growth; a cytotoxic effect on 9L cells was detected 5 days after irradiation. Significant decreases in tumoral blood volume fraction and vessel diameter were measured from 8 days after irradiation, due to loss of endothelial cells in tumors as detected by immunochemistry. Edema was observed in the normal brain exposed to both crossfired arrays about 6 weeks after irradiation. This edema was associated with changes in blood vessel morphology and an overexpression of vascular endothelial growth factor. Conversely, vascular parameters and vessel morphology in brain regions exposed to one of the two arrays were not damaged, and there was no loss of vascular endothelia. Conclusions: We show for the first time that preferential damage of MRT to tumor vessels versus preservation of radioresistant normal brain vessels contributes to the efficient palliation of 9L gliosarcomas in rats. Molecular pathways of repair mechanisms in normal and tumoral vascular networks after MRT may be essential for the improvement of such differential effects on the vasculature.

  6. Complete reversibility of physiological coronary vascular abnormalities in hypertrophied hearts produced by pressure overload in the rat.

    PubMed Central

    Isoyama, S; Ito, N; Kuroha, M; Takishima, T

    1989-01-01

    Using an experimental model of ascending aortic banding in the rat, we examined whether coronary circulation abnormalities in hypertrophied hearts are reversible after debanding. 4-wk banding produced significant increases in in vivo left ventricular (LV) pressure (194 +/- 13 vs. 114 +/- 9 mmHg in shamoperated controls) and LV dry wt/body wt (48 +/- 5% above controls). In isolated hearts perfused with Krebs-Henseleit buffer, coronary flow rate (CFR) was estimated under nonworking conditions. During maximal vasodilation after 1 min-ischemia, CFR at a coronary perfusion pressure (CPP) of 100 mmHg and CFR/myocardidial mass at CPPs of 100 and 150 mmHg decreased significantly (72 +/- 5%; 53 +/- 4 and 61 +/- 4% of controls). 1 or 4 wk after debanding, LV systolic pressures were similar to control values, and the degree of myocardial hypertrophy decreased to levels 23 +/- 6 (P less than 0.01) and 11 +/- 6% (P less than 0.01) above their control values, respectively. At 1 wk there was no significant increase in CFR/myocardial mass, compared to values in the banded group (67 +/- 8 vs. 53 +/- 4% of controls at 100 mmHg and 67 +/- 9 vs. 61 +/- 4% at 150 mmHg of CPP). At 4 wk, CFR and the ratio had increased toward normal. Thus, decreased coronary perfusion in hypertrophied hearts is completely reversible. Images PMID:2525568

  7. An integrated geometric modelling framework for patient-specific computational haemodynamic study on wide-ranged vascular network.

    PubMed

    Torii, Ryo; Oshima, Marie

    2012-01-01

    Patient-specific haemodynamic computations have been used as an effective tool in researches on cardiovascular disease associated with haemodynamics such as atherosclerosis and aneurysm. Recent development of computer resource has enabled 3D haemodynamic computations in wide-spread arterial network but there are still difficulties in modelling vascular geometry because of noise and limited resolution in medical images. In this paper, an integrated framework to model an arterial network tree for patient-specific computational haemodynamic study is developed. With this framework, 3D vascular geometry reconstruction of an arterial network and quantification of its geometric feature are aimed. The combination of 3D haemodynamic computation and vascular morphology quantification helps better understand the relationship between vascular morphology and haemodynamic force behind 'geometric risk factor' for cardiovascular diseases. The proposed method is applied to an intracranial arterial network to demonstrate its accuracy and effectiveness. The results are compared with the marching-cubes (MC) method. The comparison shows that the present modelling method can reconstruct a wide-ranged vascular network anatomically more accurate than the MC method, particularly in peripheral circulation where the image resolution is low in comparison to the vessel diameter, because of the recognition of an arterial network connectivity based on its centreline.

  8. Neonatal Brain Hemorrhage (NBH) of Prematurity: Translational Mechanisms of the Vascular-Neural Network

    PubMed Central

    Lekic, Tim; Klebe, Damon; Poblete, Roy; Krafft, Paul R.; Rolland, William B.; Tang, Jiping; Zhang, John H.

    2015-01-01

    Neonatal brain hemorrhage (NBH) of prematurity is an unfortunate consequence of preterm birth. Complications result in shunt dependence and long-term structural changes such as post-hemorrhagic hydrocephalus, periventricular leukomalacia, gliosis, and neurological dysfunction. Several animal models are available to study this condition, and many basic mechanisms, etiological factors, and outcome consequences, are becoming understood. NBH is an important clinical condition, of which treatment may potentially circumvent shunt complication, and improve functional recovery (cerebral palsy, and cognitive impairments). This review highlights key pathophysiological findings of the neonatal vascular-neural network in the context of molecular mechanisms targeting the post-hemorrhagic hydrocephalus affecting this vulnerable infant population. PMID:25620100

  9. Quantifying the bioadhesive properties of surface-modified polyurethane-urea nanoparticles in the vascular network.

    PubMed

    Melgar-Lesmes, Pedro; Morral-Ruíz, Genoveva; Solans, Conxita; García-Celma, María José

    2014-06-01

    Nanomedicine research is currently requiring new standard methods to quantify the biocompatibility and bioadhesivity of emerging biomaterials designed to be used in contact with blood or soft tissues. In this study, we used biotinylated polyurethane-urea nanoparticles as a model to examine the applicabitility of an adapted hemagglutination assay to quantify the bioadhesive potential of these nanoparticles to red blood cells and, in turn, to extrapolate this data to vascular endothelial cells. We demonstrated that biotinylated nanoparticles adsorb to human erythrocytes and preferentially gather in erythrocyte contact areas. Moreover, these nanoparticles promoted a higher percentage of pig and human erythrocyte agglutination than naked polyurethane-urea nanoparticles in a biotin concentration-dependent manner. Conversely, pegylated nanoparticles were used as a negative control of the technique thus showing decreasing hemagglutination values as compared to naked nanoparticles until a minimum threshold. Furthermore, hemagglutination assay demonstrated an excellent positive correlation with bioadhesion quantification in human endothelial cells and the endothelial layer of pig aorta thus validating the hemagglutination assay described here as a useful method for predicting nanoparticle bioadhesivity to vascular endothelium. Therefore, the methodology described here is a versatile and straightforward method that allows evaluating the bioadhesive features of surface-modified polyurethane-urea nanoparticles in contact with blood and the vascular network and appears as a powerful tool to better design any drug delivery systems or implantable devices for biomedical applications.

  10. Increased Lung Expression of Anti-Angiogenic Factors in Down Syndrome: Potential Role in Abnormal Lung Vascular Growth and the Risk for Pulmonary Hypertension

    PubMed Central

    Galambos, Csaba; Minic, Angela D.; Bush, Douglas; Nguyen, Dominique; Dodson, Blair; Seedorf, Gregory; Abman, Steven H.

    2016-01-01

    Background and Aims Infants with Down syndrome (DS) or Trisomy 21, are at high risk for developing pulmonary arterial hypertension (PAH), but mechanisms that increase susceptibility are poorly understood. Laboratory studies have shown that early disruption of angiogenesis during development impairs vascular and alveolar growth and causes PAH. Human chromosome 21 encodes known anti-angiogenic factors, including collagen18a1 (endostatin, ES), ß-amyloid peptide (BAP) and Down Syndrome Critical Region 1 (DSCR-1). Therefore, we hypothesized that fetal lungs from subjects with DS are characterized by early over-expression of anti-angiogenic factors and have abnormal lung vascular growth in utero. Methods Human fetal lung tissue from DS and non-DS subjects were obtained from a biorepository. Quantitative reverse transcriptase PCR (qRT-PCR) was performed to assay 84 angiogenesis-associated genes and individual qRT-PCR was performed for ES, amyloid protein precursor (APP) and DSCR1. Western blot analysis (WBA) was used to assay lung ES, APP and DSCR-1 protein contents. Lung vessel density and wall thickness were determined by morphometric analysis. Results The angiogenesis array identified up-regulation of three anti-angiogenic genes: COL18A1 (ES), COL4A3 (tumstatin) and TIMP3 (tissue inhibitor of metallopeptidase 3) in DS lungs. Single qRT-PCR and WBA showed striking elevations of ES and APP mRNA (p = 0.022 and p = 0.001) and protein (p = 0.040 and p = 0.002; respectively). Vessel density was reduced (p = 0.041) and vessel wall thickness was increased in DS lung tissue (p = 0.033) when compared to non-DS subjects. Conclusions We conclude that lung anti-angiogenic factors, including COL18A1 (ES), COL4A3, TIMP3 and APP are over-expressed and fetal lung vessel growth is decreased in subjects with DS. We speculate that increased fetal lung anti-angiogenic factor expression due to trisomy 21 impairs lung vascular growth and signaling, which impairs alveolarization and

  11. Nitrogen impacts on vascular plants in Britain: an analysis of two national observation networks

    NASA Astrophysics Data System (ADS)

    Henrys, P. A.; Stevens, C. J.; Smart, S. M.; Maskell, L. C.; Walker, K. J.; Preston, C. D.; Crowe, A.; Rowe, E.; Gowing, D. J.; Emmett, B. A.

    2011-07-01

    Large areas of the United Kingdom currently have nitrogen (N) deposition at rates which exceed the thresholds above which there is risk of damage to sensitive components of the ecosystem (critical loads), and are predicted to continue to do so. Previous studies have shown that this excess N can be very damaging to semi-natural ecosystems. However, such studies have focussed primarily on the relationship of species richness to nitrogen, possibly missing the risk that increased deposition can have on individual plant species. To address this gap in knowledge, we used data from two national observation networks over Great Britain: the vascular plant database and the Botanical Society of the British Isles local change network to examine the response of individual vascular plant species to nitrogen in acid grasslands, calcareous grasslands and heathlands. Presence absence records of individual species, along with mean Ellenberg scores, within 10 km hectads were modelled against N deposition whilst at the same time controlling for the effects of climate, land use and sulphur deposition using generalised additive models. Ellenberg N showed a significant increase with increasing N deposition in almost all habitats across both surveys. Many individual species showed strong relationships with N deposition and clear negative trends in species prevalence to increasing nitrogen were found in all habitats. Species that showed negative relationships to N showed signs of decline at low levels, far below the current critical load levels.

  12. Two-dimensional segmentation of the retinal vascular network from optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Rodrigues, Pedro; Guimarães, Pedro; Santos, Torcato; Simão, Sílvia; Miranda, Telmo; Serranho, Pedro; Bernardes, Rui

    2013-12-01

    The automatic segmentation of the retinal vascular network from ocular fundus images has been performed by several research groups. Although different approaches have been proposed for traditional imaging modalities, only a few have addressed this problem for optical coherence tomography (OCT). Furthermore, these approaches were focused on the optic nerve head region. Compared to color fundus photography and fluorescein angiography, two-dimensional ocular fundus reference images computed from three-dimensional OCT data present additional problems related to system lateral resolution, image contrast, and noise. Specifically, the combination of system lateral resolution and vessel diameter in the macular region renders the process particularly complex, which might partly explain the focus on the optic disc region. In this report, we describe a set of features computed from standard OCT data of the human macula that are used by a supervised-learning process (support vector machines) to automatically segment the vascular network. For a set of macular OCT scans of healthy subjects and diabetic patients, the proposed method achieves 98% accuracy, 99% specificity, and 83% sensitivity. This method was also tested on OCT data of the optic nerve head region achieving similar results.

  13. Vascular ring (image)

    MedlinePlus

    Vascular ring is a term used to describe a number of abnormal formations of the aorta, the large artery ... the pulmonary artery. The abnormal vessel(s) forms a ring, which encircles and may press down on the ...

  14. Small-World Brain Network and Dynamic Functional Distribution in Patients with Subcortical Vascular Cognitive Impairment

    PubMed Central

    Yu, Yongqiang; Zhou, Xia; Wang, Haibao; Hu, Xiaopeng; Zhu, Xiaoqun; Xu, Liyan; Zhang, Chao; Sun, Zhongwu

    2015-01-01

    To investigate the topological properties of the functional connectivity and their relationships with cognition impairment in subcortical vascular cognitive impairment (SVCI) patients, resting-state fMRI and graph theory approaches were employed in 23 SVCI patients and 20 healthy controls. Functional connectivity between 90 brain regions was estimated using bivariate correlation analysis and thresholded to construct a set of undirected graphs. Moreover, all of them were subjected to a battery of cognitive assessment, and the correlations between graph metrics and cognitive performance were further analyzed. Our results are as follows: functional brain networks of both SVCI patients and controls showed small-world attributes over a range of thresholds(0.15≤sparsity≤0.40). However, global topological organization of the functional brain networks in SVCI was significantly disrupted, as indicated by reduced global and local efficiency, clustering coefficients and increased characteristic path lengths relative to normal subjects. The decreased activity areas in SVCI predominantly targeted in the frontal-temporal lobes, while subcortical regions showed increased topological properties, which are suspected to compensate for the inefficiency of the functional network. We also demonstrated that altered brain network properties in SVCI are closely correlated with general cognitive and praxis dysfunction. The disruption of whole-brain topological organization of the functional connectome provides insight into the functional changes in the human brain in SVCI. PMID:26132397

  15. Annual Research Review: Growth connectomics – the organization and reorganization of brain networks during normal and abnormal development

    PubMed Central

    Vértes, Petra E; Bullmore, Edward T

    2015-01-01

    Background We first give a brief introduction to graph theoretical analysis and its application to the study of brain network topology or connectomics. Within this framework, we review the existing empirical data on developmental changes in brain network organization across a range of experimental modalities (including structural and functional MRI, diffusion tensor imaging, magnetoencephalography and electroencephalography in humans). Synthesis We discuss preliminary evidence and current hypotheses for how the emergence of network properties correlates with concomitant cognitive and behavioural changes associated with development. We highlight some of the technical and conceptual challenges to be addressed by future developments in this rapidly moving field. Given the parallels previously discovered between neural systems across species and over a range of spatial scales, we also review some recent advances in developmental network studies at the cellular scale. We highlight the opportunities presented by such studies and how they may complement neuroimaging in advancing our understanding of brain development. Finally, we note that many brain and mind disorders are thought to be neurodevelopmental in origin and that charting the trajectory of brain network changes associated with healthy development also sets the stage for understanding abnormal network development. Conclusions We therefore briefly review the clinical relevance of network metrics as potential diagnostic markers and some recent efforts in computational modelling of brain networks which might contribute to a more mechanistic understanding of neurodevelopmental disorders in future. PMID:25441756

  16. Interdisciplinary networks for the treatment of childhood pulmonary vascular disease: what pulmonary hypertension doctors can learn from pediatric oncologists.

    PubMed

    Hansmann, Georg

    2013-12-01

    The pathobiology of pulmonary arterial hypertension (PAH) is complex and multifactorial. None of the current therapies has been shown to be universally effective or able to reverse advanced pulmonary vascular disease, characterized by plexiform vascular lesions, or to prevent right ventricular failure in advanced PAH. It is thus unlikely that only one factor, pathway, or gene mutation will explain all forms and cases. Pediatric oncologists recognized a need for intensified, collaborative research within their field more than 40 years ago and implemented major clinical and translational networks worldwide to achieve evidence-based "tailored therapies." The similarities in the pathobiology (e.g., increased proliferation and resistance to apoptosis in vascular cells and perivascular inflammation) and the uncertainties in the proper treatment of both cancer and pulmonary hypertension (PH) have led to the idea of building interdisciplinary networks among PH centers to achieve rapid translation of basic research findings, optimal diagnostic algorithms, and significant, sustained treatment results. Such networks leading to patient registries, clinical trials, drug development, and innovative, effective therapies are urgently needed for the care of children with PH. This article reviews the current status, limitations, and recent developments in the field of pediatric PH. It is suggested that the oncologists' exemplary networks, concepts, and results in the treatment of acute lymphoblastic leukemia are applicable to future networks and innovative therapies for pediatric pulmonary hypertensive vascular disease and right ventricular dysfunction.

  17. Vascular neural network phenotypic transformation after traumatic injury: potential role in long-term sequelae.

    PubMed

    Badaut, J; Bix, G J

    2014-06-01

    The classical neurovascular unit (NVU), composed primarily of endothelium, astrocytes, and neurons, could be expanded to include smooth muscle and perivascular nerves present in both the up- and downstream feeding blood vessels (arteries and veins). The extended NVU, which can be defined as the vascular neural network (VNN), may represent a new physiological unit to consider for therapeutic development in stroke, traumatic brain injury, and other brain disorders (Zhang et al., Nat Rev Neurol 8(12):711-716, 2012). This review is focused on traumatic brain injury and resultant post-traumatic changes in cerebral blood flow, smooth muscle cells, matrix, blood-brain barrier structures and function, and the association of these changes with cognitive outcomes as described in clinical and experimental reports. We suggest that studies characterizing TBI outcomes should increase their focus on changes to the VNN, as this may yield meaningful therapeutic targets to resolve posttraumatic dysfunction.

  18. Abnormal Functional Activation and Connectivity in the Working Memory Network in Early-Onset Schizophrenia

    ERIC Educational Resources Information Center

    Kyriakopoulos, Marinos; Dima, Danai; Roiser, Jonathan P.; Corrigall, Richard; Barker, Gareth J.; Frangou, Sophia

    2012-01-01

    Objective: Disruption within the working memory (WM) neural network is considered an integral feature of schizophrenia. The WM network, and the dorsolateral prefrontal cortex (DLPFC) in particular, undergo significant remodeling in late adolescence. Potential interactions between developmental changes in the WM network and disease-related…

  19. Functional Brain Network Abnormalities during Verbal Working Memory Performance in Adolescents and Young Adults with Dyslexia

    ERIC Educational Resources Information Center

    Wolf, Robert Christian; Sambataro, Fabio; Lohr, Christina; Steinbrink, Claudia; Martin, Claudia; Vasic, Nenad

    2010-01-01

    Behavioral and functional neuroimaging studies indicate deficits in verbal working memory (WM) and frontoparietal dysfunction in individuals with dyslexia. Additionally, structural brain abnormalities in dyslexics suggest a dysconnectivity of brain regions associated with phonological processing. However, little is known about the functional…

  20. An image-based software tool for screening retinal fundus images using vascular morphology and network transport analysis

    NASA Astrophysics Data System (ADS)

    Clark, Richard D.; Dickrell, Daniel J.; Meadows, David L.

    2014-03-01

    As the number of digital retinal fundus images taken each year grows at an increasing rate, there exists a similarly increasing need for automatic eye disease detection through image-based analysis. A new method has been developed for classifying standard color fundus photographs into both healthy and diseased categories. This classification was based on the calculated network fluid conductance, a function of the geometry and connectivity of the vascular segments. To evaluate the network resistance, the retinal vasculature was first manually separated from the background to ensure an accurate representation of the geometry and connectivity. The arterial and venous networks were then semi-automatically separated into two separate binary images. The connectivity of the arterial network was then determined through a series of morphological image operations. The network comprised of segments of vasculature and points of bifurcation, with each segment having a characteristic geometric and fluid properties. Based on the connectivity and fluid resistance of each vascular segment, an arterial network flow conductance was calculated, which described the ease with which blood can pass through a vascular system. In this work, 27 eyes (13 healthy and 14 diabetic) from patients roughly 65 years in age were evaluated using this methodology. Healthy arterial networks exhibited an average fluid conductance of 419 ± 89 μm3/mPa-s while the average network fluid conductance of the diabetic set was 165 ± 87 μm3/mPa-s (p < 0.001). The results of this new image-based software demonstrated an ability to automatically, quantitatively and efficiently screen diseased eyes from color fundus imagery.

  1. Vascular risk factors, cerebrovascular reactivity, and the default-mode brain network

    PubMed Central

    Haight, Thaddeus J; Bryan, R Nick; Erus, Guray; Davatzikos, Christos; Jacobs, David R; D'Esposito, Mark; Lewis, Cora E; Launer, Lenore J

    2015-01-01

    Cumulating evidence from epidemiologic studies implicates cardiovascular health and cerebrovascular function in several brain diseases in late life. We examined vascular risk factors with respect to a cerebrovascular measure of brain functioning in subjects in mid-life, which could represent a marker of brain changes in later life. Breath-hold functional MRI (fMRI) was performed in 541 women and men (mean age 50.4 years) from the Coronary Artery Risk Development in Young Adults (CARDIA) Brain MRI sub-study. Cerebrovascular reactivity (CVR) was quantified as percentage change in blood-oxygen level dependent (BOLD) signal in activated voxels, which was mapped to a common brain template and log-transformed. Mean CVR was calculated for anatomic regions underlying the default-mode network (DMN) - a network implicated in AD and other brain disorders - in addition to areas considered to be relatively spared in the disease (e.g. occipital lobe), which were utilized as reference regions. Mean CVR was significantly reduced in the posterior cingulate/precuneus (β = -0.063, 95% CI: - 0.106, -0.020), anterior cingulate (β = -0.055, 95% CI: -0.101, -0.010), and medial frontal lobe (β = -0.050, 95% CI: -0.092, -0.008) relative to mean CVR in the occipital lobe, after adjustment for age, sex, race, education, and smoking status, in subjects with pre-hypertension/hypertension compared to normotensive subjects. By contrast, mean CVR was lower, but not significantly, in the inferior parietal lobe (β = -0.024, 95% CI: -0.062, 0.014) and the hippocampus (β = -0.006, 95% CI: -0.062, 0.050) relative to mean CVR in the occipital lobe. Similar results were observed in subjects with diabetes and dyslipidemia compared to those without these conditions, though the differences were non-significant. Reduced CVR may represent diminished vascular functionality for the DMN for individuals with prehypertension/ hypertension in mid-life, and may serve as a preclinical marker for brain

  2. Polymicrogyric Cortex may Predispose to Seizures via Abnormal Network Topology: An fMRI Connectomics Study.

    PubMed

    Sethi, Moksh; Pedersen, Mangor; Jackson, Graeme D

    2016-03-01

    Polymicrogyria is a significant malformation of cortical development with a high incidence of epilepsy and cognitive deficits. Graph theoretic analysis is a useful approach to studying network organization in brain disorders. In this study, we used task-free functional magnetic resonance imaging (fMRI) data from four patients with polymicrogyria and refractory epilepsy. Gray matter masks from structural MRI data were parcellated into 1,024 network nodes. Functional "connectomes" were obtained based on fMRI time series between the parcellated network nodes; network analysis was conducted using clustering coefficient, path length, node degree, and participation coefficient. These graph metrics were compared between nodes within polymicrogyric cortex and normal brain tissue in contralateral homologous cortical regions. Polymicrogyric nodes showed significantly increased clustering coefficient and characteristic path length. This is the first study using functional connectivity analysis in polymicrogyria--our results indicate a shift toward a regular network topology in polymicrogyric nodes. Regularized network topology has been demonstrated previously in patients with focal epilepsy and during focal seizures. Thus, we postulate that these network alterations predispose to seizures and may be relevant to cognitive deficits in patients with polymicrogyria.

  3. Polymicrogyric Cortex may Predispose to Seizures via Abnormal Network Topology: An fMRI Connectomics Study.

    PubMed

    Sethi, Moksh; Pedersen, Mangor; Jackson, Graeme D

    2016-03-01

    Polymicrogyria is a significant malformation of cortical development with a high incidence of epilepsy and cognitive deficits. Graph theoretic analysis is a useful approach to studying network organization in brain disorders. In this study, we used task-free functional magnetic resonance imaging (fMRI) data from four patients with polymicrogyria and refractory epilepsy. Gray matter masks from structural MRI data were parcellated into 1,024 network nodes. Functional "connectomes" were obtained based on fMRI time series between the parcellated network nodes; network analysis was conducted using clustering coefficient, path length, node degree, and participation coefficient. These graph metrics were compared between nodes within polymicrogyric cortex and normal brain tissue in contralateral homologous cortical regions. Polymicrogyric nodes showed significantly increased clustering coefficient and characteristic path length. This is the first study using functional connectivity analysis in polymicrogyria--our results indicate a shift toward a regular network topology in polymicrogyric nodes. Regularized network topology has been demonstrated previously in patients with focal epilepsy and during focal seizures. Thus, we postulate that these network alterations predispose to seizures and may be relevant to cognitive deficits in patients with polymicrogyria. PMID:26763051

  4. Detecting and mitigating abnormal events in large scale networks: budget constrained placement on smart grids

    SciTech Connect

    Santhi, Nandakishore; Pan, Feng

    2010-10-19

    Several scenarios exist in the modern interconnected world which call for an efficient network interdiction algorithm. Applications are varied, including various monitoring and load shedding applications on large smart energy grids, computer network security, preventing the spread of Internet worms and malware, policing international smuggling networks, and controlling the spread of diseases. In this paper we consider some natural network optimization questions related to the budget constrained interdiction problem over general graphs, specifically focusing on the sensor/switch placement problem for large-scale energy grids. Many of these questions turn out to be computationally hard to tackle. We present a particular form of the interdiction question which is practically relevant and which we show as computationally tractable. A polynomial-time algorithm will be presented for solving this problem.

  5. In-silico analysis on biofabricating vascular networks using kinetic Monte Carlo simulations.

    PubMed

    Sun, Yi; Yang, Xiaofeng; Wang, Qi

    2014-03-01

    We present a computational modeling approach to study the fusion of multicellular aggregate systems in a novel scaffold-less biofabrication process, known as 'bioprinting'. In this novel technology, live multicellular aggregates are used as fundamental building blocks to make tissues or organs (collectively known as the bio-constructs,) via the layer-by-layer deposition technique or other methods; the printed bio-constructs embedded in maturogens, consisting of nutrient-rich bio-compatible hydrogels, are then placed in bioreactors to undergo the cellular aggregate fusion process to form the desired functional bio-structures. Our approach reported here is an agent-based modeling method, which uses the kinetic Monte Carlo (KMC) algorithm to evolve the cellular system on a lattice. In this method, the cells and the hydrogel media, in which cells are embedded, are coarse-grained to material's points on a three-dimensional (3D) lattice, where the cell-cell and cell-medium interactions are quantified by adhesion and cohesion energies. In a multicellular aggregate system with a fixed number of cells and fixed amount of hydrogel media, where the effect of cell differentiation, proliferation and death are tactically neglected, the interaction energy is primarily dictated by the interfacial energy between cell and cell as well as between cell and medium particles on the lattice, respectively, based on the differential adhesion hypothesis. By using the transition state theory to track the time evolution of the multicellular system while minimizing the interfacial energy, KMC is shown to be an efficient time-dependent simulation tool to study the evolution of the multicellular aggregate system. In this study, numerical experiments are presented to simulate fusion and cell sorting during the biofabrication process of vascular networks, in which the bio-constructs are fabricated via engineering designs. The results predict the feasibility of fabricating the vascular structures

  6. Modeling Abnormal Priming in Alzheimer's Patients with a Free Association Network

    PubMed Central

    Borge-Holthoefer, Javier; Moreno, Yamir; Arenas, Alex

    2011-01-01

    Alzheimer's Disease irremediably alters the proficiency of word search and retrieval processes even at its early stages. Such disruption can sometimes be paradoxical in specific language tasks, for example semantic priming. Here we focus in the striking side-effect of hyperpriming in Alzheimer's Disease patients, which has been well-established in the literature for a long time. Previous studies have evidenced that modern network theory can become a powerful complementary tool to gain insight in cognitive phenomena. Here, we first show that network modeling is an appropriate approach to account for semantic priming in normal subjects. Then we turn to priming in degraded cognition: hyperpriming can be readily understood in the scope of a progressive degradation of the semantic network structure. We compare our simulation results with previous empirical observations in diseased patients finding a qualitative agreement. The network approach presented here can be used to accommodate current theories about impaired cognition, and towards a better understanding of lexical organization in healthy and diseased patients. PMID:21829639

  7. Abnormalities in fronto-striatal connectivity within language networks relate to differences in grey-matter heterogeneity in Asperger syndrome.

    PubMed

    Radulescu, Eugenia; Minati, Ludovico; Ganeshan, Balaji; Harrison, Neil A; Gray, Marcus A; Beacher, Felix D C C; Chatwin, Chris; Young, Rupert C D; Critchley, Hugo D

    2013-01-01

    Asperger syndrome (AS) is an Autism Spectrum Disorder (ASD) characterised by qualitative impairment in the development of emotional and social skills with relative preservation of general intellectual abilities, including verbal language. People with AS may nevertheless show atypical language, including rate and frequency of speech production. We previously observed that abnormalities in grey matter homogeneity (measured with texture analysis of structural MR images) in AS individuals when compared with controls are also correlated with the volume of caudate nucleus. Here, we tested a prediction that these distributed abnormalities in grey matter compromise the functional integrity of brain networks supporting verbal communication skills. We therefore measured the functional connectivity between caudate nucleus and cortex during a functional neuroimaging study of language generation (verbal fluency), applying psycho-physiological interaction (PPI) methods to test specifically for differences attributable to grey matter heterogeneity in AS participants. Furthermore, we used dynamic causal modelling (DCM) to characterise the causal directionality of these differences in interregional connectivity during word production. Our results revealed a diagnosis-dependent influence of grey matter heterogeneity on the functional connectivity of the caudate nuclei with right insula/inferior frontal gyrus and anterior cingulate, respectively with the left superior frontal gyrus and right precuneus. Moreover, causal modelling of interactions between inferior frontal gyri, caudate and precuneus, revealed a reliance on bottom-up (stimulus-driven) connections in AS participants that contrasted with a dominance of top-down (cognitive control) connections from prefrontal cortex observed in control participants. These results provide detailed support for previously hypothesised central disconnectivity in ASD and specify discrete brain network targets for diagnosis and therapy in ASD.

  8. Interconnection between biological abnormalities in borderline personality disorder: use of the Bayesian networks model.

    PubMed

    De la Fuente, José Manuel; Bengoetxea, Endika; Navarro, Felipe; Bobes, Julio; Alarcón, Renato Daniel

    2011-04-30

    There is agreement in that strengthening the sets of neurobiological data would reinforce the diagnostic objectivity of many psychiatric entities. This article attempts to use this approach in borderline personality disorder (BPD). Assuming that most of the biological findings in BPD reflect common underlying pathophysiological processes we hypothesized that most of the data involved in the findings would be statistically interconnected and interdependent, indicating biological consistency for this diagnosis. Prospectively obtained data on scalp and sleep electroencephalography (EEG), clinical neurologic soft signs, the dexamethasone suppression and thyrotropin-releasing hormone stimulation tests of 20 consecutive BPD patients were used to generate a Bayesian network model, an artificial intelligence paradigm that visually illustrates eventual associations (or inter-dependencies) between otherwise seemingly unrelated variables. The Bayesian network model identified relationships among most of the variables. EEG and TSH were the variables that influence most of the others, especially sleep parameters. Neurological soft signs were linked with EEG, TSH, and sleep parameters. The results suggest the possibility of using objective neurobiological variables to strengthen the validity of future diagnostic criteria and nosological characterization of BPD.

  9. Large-scale brain network abnormalities in Huntington's disease revealed by structural covariance.

    PubMed

    Minkova, Lora; Eickhoff, Simon B; Abdulkadir, Ahmed; Kaller, Christoph P; Peter, Jessica; Scheller, Elisa; Lahr, Jacob; Roos, Raymund A; Durr, Alexandra; Leavitt, Blair R; Tabrizi, Sarah J; Klöppel, Stefan

    2016-01-01

    Huntington's disease (HD) is a progressive neurodegenerative disorder that can be diagnosed with certainty decades before symptom onset. Studies using structural MRI have identified grey matter (GM) loss predominantly in the striatum, but also involving various cortical areas. So far, voxel-based morphometric studies have examined each brain region in isolation and are thus unable to assess the changes in the interrelation of brain regions. Here, we examined the structural covariance in GM volumes in pre-specified motor, working memory, cognitive flexibility, and social-affective networks in 99 patients with manifest HD (mHD), 106 presymptomatic gene mutation carriers (pre-HD), and 108 healthy controls (HC). After correction for global differences in brain volume, we found that increased GM volume in one region was associated with increased GM volume in another. When statistically comparing the groups, no differences between HC and pre-HD were observed, but increased positive correlations were evident for mHD, relative to pre-HD and HC. These findings could be explained by a HD-related neuronal loss heterogeneously affecting the examined network at the pre-HD stage, which starts to dominate structural covariance globally at the manifest stage. Follow-up analyses identified structural connections between frontoparietal motor regions to be linearly modified by disease burden score (DBS). Moderator effects of disease load burden became significant at a DBS level typically associated with the onset of unequivocal HD motor signs. Together with existing findings from functional connectivity analyses, our data indicates a critical role of these frontoparietal regions for the onset of HD motor signs.

  10. Neuropathological and neuromorphometric abnormalities in bipolar disorder: view from the medial prefrontal cortical network.

    PubMed

    Savitz, Jonathan B; Price, Joseph L; Drevets, Wayne C

    2014-05-01

    The question of whether BD is primarily a developmental disorder or a progressive, neurodegenerative disorder remains unresolved. Here, we review the morphometric postmortem and neuroimaging literature relevant to the neuropathology of bipolar disorder (BD). We focus on the medial prefrontal cortex (mPFC) network, a key system in the regulation of emotional, behavioral, endocrine, and innate immunological responses to stress. We draw four main conclusions: the mPFC is characterized by (1) a decrease in volume, (2) reductions in neuronal size, and/or changes in neuronal density, (3) reductions in glial cell density, and (4) changes in gene expression. These data suggest the presence of dendritic atrophy of neurons and the loss of oligodendroglial cells in BD, although some data additionally suggest a reduction in the cell counts of specific subpopulations of GABAergic interneurons. Based on the weight of the postmortem and neuroimaging literature discussed herein, we favor a complex hypothesis that BD primarily constitutes a developmental disorder, but that additional, progressive, histopathological processes also are associated with recurrent or chronic illness. Conceivably BD may be best conceptualized as a progressive neurodevelopmental disorder.

  11. Sertoli Cells Modulate Testicular Vascular Network Development, Structure, and Function to Influence Circulating Testosterone Concentrations in Adult Male Mice.

    PubMed

    Rebourcet, Diane; Wu, Junxi; Cruickshanks, Lyndsey; Smith, Sarah E; Milne, Laura; Fernando, Anuruddika; Wallace, Robert J; Gray, Calum D; Hadoke, Patrick W F; Mitchell, Rod T; O'Shaughnessy, Peter J; Smith, Lee B

    2016-06-01

    The testicular vasculature forms a complex network, providing oxygenation, micronutrients, and waste clearance from the testis. The vasculature is also instrumental to testis function because it is both the route by which gonadotropins are delivered to the testis and by which T is transported away to target organs. Whether Sertoli cells play a role in regulating the testicular vasculature in postnatal life has never been unequivocally demonstrated. In this study we used models of acute Sertoli cell ablation and acute germ cell ablation to address whether Sertoli cells actively influence vascular structure and function in the adult testis. Our findings suggest that Sertoli cells play a key role in supporting the structure of the testicular vasculature. Ablating Sertoli cells (and germ cells) or germ cells alone results in a similar reduction in testis size, yet only the specific loss of Sertoli cells leads to a reduction in total intratesticular vascular volume, the number of vascular branches, and the numbers of small microvessels; loss of germ cells alone has no effect on the testicular vasculature. These perturbations to the testicular vasculature leads to a reduction in fluid exchange between the vasculature and testicular interstitium, which reduces gonadotropin-stimulated circulating T concentrations, indicative of reduced Leydig cell stimulation and/or reduced secretion of T into the vasculature. These findings describe a new paradigm by which the transport of hormones and other factors into and out of the testis may be influenced by Sertoli cells and highlights these cells as potential targets for enhancing this endocrine relationship.

  12. PlexinD1 is required for proper patterning of the periocular vascular network and for the establishment of corneal avascularity during avian ocular development.

    PubMed

    Kwiatkowski, Sam C; Ojeda, Ana F; Lwigale, Peter Y

    2016-03-01

    The anterior eye is comprised of an avascular cornea surrounded by a dense periocular vascular network and therefore serves as an excellent model for angiogenesis. Although signaling through PlexinD1 underlies various vascular patterning events during embryonic development, its role during the formation of the periocular vascular network is yet to be determined. Our recent study showed that PlexinD1 mRNA is expressed by periocular angioblasts and blood vessels during ocular vasculogenesis in patterns that suggest its involvement with Sema3 ligands that are concurrently expressed in the anterior eye. In this study, we used in vivo knockdown experiments to determine the role of PlexinD1 during vascular patterning in the anterior eye of the developing avian embryos. Knockdown of PlexinD1 in the anterior eye caused mispatterning of the vascular network in the presumptive iris, which was accompanied by lose of vascular integrity and profuse hemorrhaging in the anterior chamber. We also observed ectopic vascularization of the cornea in PlexinD1 knockdown eyes, which coincided with the formation of the limbal vasculature in controls. Finally we show that Sema3E and Sema3C transcripts are expressed in ocular tissue that is devoid of vasculature. These results indicate that PlexinD1 plays a critical role during vascular patterning in the iris and limbus, and is essential for the establishment of corneal avascularity during development. We conclude that PlexinD1 is involved in vascular response to antiangiogenic Sema3 signaling that guides the formation of the iris and limbal blood vessels by inhibiting VEGF signaling. PMID:26783882

  13. Abnormal Activation of the Social Brain Network in Children with Autism Spectrum Disorder: An fMRI Study

    PubMed Central

    Kim, Sun-Young; Choi, Uk-Su; Park, Sung-Yeon; Oh, Se-Hong; Yoon, Hyo-Woon; Koh, Yun-Joo; Im, Woo-Young; Park, Jee-In; Song, Dong-Ho

    2015-01-01

    Objective The aim of this study is to investigate abnormal findings of social brain network in Korean children with autism spectrum disorder (ASD) compared with typically developing children (TDC). Methods Functional magnetic resonance imaging (fMRI) was performed to examine brain activations during the processing of emotional faces (happy, fearful, and neutral) in 17 children with ASD, 24 TDC. Results When emotional face stimuli were given to children with ASD, various areas of the social brain relevant to social cognition showed reduced activation. Specifically, ASD children exhibited less activation in the right amygdala (AMY), right superior temporal sulcus (STS) and right inferior frontal gyrus (IFG) than TDC group when fearful faces were shown. Activation of left insular cortex and right IFG in response to happy faces was less in the ASD group. Similar findings were also found in left superior insular gyrus and right insula in case of neutral stimulation. Conclusion These findings suggest that children with ASD have different processing of social and emotional experience at the neural level. In other words, the deficit of social cognition in ASD could be explained by the deterioration of the capacity for visual analysis of emotional faces, the subsequent inner imitation through mirror neuron system (MNS), and the ability to transmit it to the limbic system and to process the transmitted emotion. PMID:25670944

  14. Plectin reinforces vascular integrity by mediating crosstalk between the vimentin and the actin networks

    PubMed Central

    Osmanagic-Myers, Selma; Rus, Stefanie; Wolfram, Michael; Brunner, Daniela; Goldmann, Wolfgang H.; Bonakdar, Navid; Fischer, Irmgard; Reipert, Siegfried; Zuzuarregui, Aurora; Walko, Gernot; Wiche, Gerhard

    2015-01-01

    ABSTRACT Mutations in the cytoskeletal linker protein plectin result in multisystemic diseases affecting skin and muscle with indications of additional vascular system involvement. To study the mechanisms underlying vascular disorders, we established plectin-deficient endothelial cell and mouse models. We show that apart from perturbing the vimentin cytoskeleton of endothelial cells, plectin deficiency leads to severe distortions of adherens junctions (AJs), as well as tight junctions, accompanied by an upregulation of actin stress fibres and increased cellular contractility. Plectin-deficient endothelial cell layers were more leaky and showed reduced mechanical resilience in fluid-shear stress and mechanical stretch experiments. We suggest that the distorted AJs and upregulated actin stress fibres in plectin-deficient cells are rooted in perturbations of the vimentin cytoskeleton, as similar phenotypes could be mimicked in wild-type cells by disruption of vimentin filaments. In vivo studies in endothelium-restricted conditional plectin-knockout mice revealed significant distortions of AJs in stress-prone aortic arch regions and increased pulmonary vascular leakage. Our study opens a new perspective on cytoskeleton-controlled vascular permeability, where a plectin-organized vimentin scaffold keeps actomyosin contractility ‘in-check’ and maintains AJ homeostasis. PMID:26519478

  15. Network Meta-analysis of Randomized Trials on the Safety of Vascular Closure Devices for Femoral Arterial Puncture Site Haemostasis.

    PubMed

    Jiang, Jun; Zou, Junjie; Ma, Hao; Jiao, Yuanyong; Yang, Hongyu; Zhang, Xiwei; Miao, Yi

    2015-09-08

    The safety of vascular closure devices (VCDs) is still debated. The emergence of more related randomized controlled trials (RCTs) and newer VCDs makes it necessary to further evaluate the safety of VCDs. Relevant RCTs were identified by searching PubMed, EMBASE, Google Scholar and the Cochrane Central Register of Controlled Trials electronic databases updated in December 2014. Traditional and network meta-analyses were conducted to evaluate the rate of combined adverse vascular events (CAVEs) and haematomas by calculating the risk ratios and 95% confidence intervals. Forty RCTs including 16868 patients were included. Traditional meta-analysis demonstrated that there was no significant difference in the rate of CAVEs between all the VCDs and manual compression (MC). Subgroup analysis showed that FemoSeal and VCDs reported after the year 2005 reduced CAVEs. Moreover, the use of VCDs reduced the risk of haematomas compared with MC. Network meta-analysis showed that AngioSeal, which might be the best VCD among all the included VCDs, was associated with reduced rates of both CAVE and haematomas compared with MC. In conclusion, the use of VCDs is associated with a decreased risk of haematomas, and FemoSeal and AngioSeal appears to be better than MC for reducing the rate of CAVEs.

  16. Inner Ear Conductive Hearing Loss and Unilateral Pulsatile Tinnitus Associated with a Dural Arteriovenous Fistula: Case Based Review and Analysis of Relationship between Intracranial Vascular Abnormalities and Inner Ear Fluids

    PubMed Central

    Cassandro, Ettore; Cassandro, Claudia; Sequino, Giuliano; Scarpa, Alfonso; Petrolo, Claudio; Chiarella, Giuseppe

    2015-01-01

    While pulsatile tinnitus (PT) and dural arteriovenous fistula (DAVF) are not rarely associated, the finding of a conductive hearing loss (CHL) in this clinical picture is unusual. Starting from a case of CHL and PT, diagnosed to be due to a DAVF, we analyzed relationship between intracranial vascular abnormalities and inner ear fluids. DAVF was treated with endovascular embolization. Following this, there was a dramatic recovery of PT and of CHL, confirming their cause-effect link with DAVF. We critically evaluated the papers reporting this association. This is the first case of CHL associated with PT and DAVF. We describe the most significant experiences and theories reported in literature, with a personal analysis about the possible relationship between vascular intracranial system and labyrinthine fluids. In conclusion, we believe that this association may be a challenge for otolaryngologists. So we suggest to consider the possibility of a DAVF or other AVMs when PT is associated with CHL, without alterations of tympanic membrane and middle ear tests. PMID:26693371

  17. Causal biological network database: a comprehensive platform of causal biological network models focused on the pulmonary and vascular systems

    PubMed Central

    Boué, Stéphanie; Talikka, Marja; Westra, Jurjen Willem; Hayes, William; Di Fabio, Anselmo; Park, Jennifer; Schlage, Walter K.; Sewer, Alain; Fields, Brett; Ansari, Sam; Martin, Florian; Veljkovic, Emilija; Kenney, Renee; Peitsch, Manuel C.; Hoeng, Julia

    2015-01-01

    With the wealth of publications and data available, powerful and transparent computational approaches are required to represent measured data and scientific knowledge in a computable and searchable format. We developed a set of biological network models, scripted in the Biological Expression Language, that reflect causal signaling pathways across a wide range of biological processes, including cell fate, cell stress, cell proliferation, inflammation, tissue repair and angiogenesis in the pulmonary and cardiovascular context. This comprehensive collection of networks is now freely available to the scientific community in a centralized web-based repository, the Causal Biological Network database, which is composed of over 120 manually curated and well annotated biological network models and can be accessed at http://causalbionet.com. The website accesses a MongoDB, which stores all versions of the networks as JSON objects and allows users to search for genes, proteins, biological processes, small molecules and keywords in the network descriptions to retrieve biological networks of interest. The content of the networks can be visualized and browsed. Nodes and edges can be filtered and all supporting evidence for the edges can be browsed and is linked to the original articles in PubMed. Moreover, networks may be downloaded for further visualization and evaluation. Database URL: http://causalbionet.com PMID:25887162

  18. Causal biological network database: a comprehensive platform of causal biological network models focused on the pulmonary and vascular systems.

    PubMed

    Boué, Stéphanie; Talikka, Marja; Westra, Jurjen Willem; Hayes, William; Di Fabio, Anselmo; Park, Jennifer; Schlage, Walter K; Sewer, Alain; Fields, Brett; Ansari, Sam; Martin, Florian; Veljkovic, Emilija; Kenney, Renee; Peitsch, Manuel C; Hoeng, Julia

    2015-01-01

    With the wealth of publications and data available, powerful and transparent computational approaches are required to represent measured data and scientific knowledge in a computable and searchable format. We developed a set of biological network models, scripted in the Biological Expression Language, that reflect causal signaling pathways across a wide range of biological processes, including cell fate, cell stress, cell proliferation, inflammation, tissue repair and angiogenesis in the pulmonary and cardiovascular context. This comprehensive collection of networks is now freely available to the scientific community in a centralized web-based repository, the Causal Biological Network database, which is composed of over 120 manually curated and well annotated biological network models and can be accessed at http://causalbionet.com. The website accesses a MongoDB, which stores all versions of the networks as JSON objects and allows users to search for genes, proteins, biological processes, small molecules and keywords in the network descriptions to retrieve biological networks of interest. The content of the networks can be visualized and browsed. Nodes and edges can be filtered and all supporting evidence for the edges can be browsed and is linked to the original articles in PubMed. Moreover, networks may be downloaded for further visualization and evaluation. Database URL: http://causalbionet.com

  19. Symplasmic networks in secondary vascular tissues: parenchyma distribution and activity supporting long-distance transport.

    PubMed

    Spicer, Rachel

    2014-04-01

    Stems that develop secondary vascular tissue (i.e. xylem and phloem derived from the vascular cambium) have unique demands on transport owing to their mass and longevity. Transport of water and assimilates must occur over long distances, while the increasing physical separation of xylem and phloem requires radial transport. Developing secondary tissue is itself a strong sink positioned between xylem and phloem along the entire length of the stem, and the integrity of these transport tissues must be maintained and protected for years if not decades. Parenchyma cells form an interconnected three-dimensional lattice throughout secondary xylem and phloem and perform critical roles in all of these tasks, yet our understanding of their physiology, the nature of their symplasmic connections, and their activity at the symplast-apoplast interface is very limited. This review highlights key historical work as well as current research on the structure and function of parenchyma in secondary vascular tissue in the hopes of spurring renewed interest in this area, which has important implications for whole-plant transport processes and resource partitioning.

  20. Asymmetries arising from the space-filling nature of vascular networks.

    PubMed

    Hunt, David; Savage, Van M

    2016-06-01

    Cardiovascular networks span the body by branching across many generations of vessels. The resulting structure delivers blood over long distances to supply all cells with oxygen via the relatively short-range process of diffusion at the capillary level. The structural features of the network that accomplish this density and ubiquity of capillaries are often called space-filling. There are multiple strategies to fill a space, but some strategies do not lead to biologically adaptive structures by requiring too much construction material or space, delivering resources too slowly, or using too much power to move blood through the system. We empirically measure the structure of real networks (18 humans and 1 mouse) and compare these observations with predictions of model networks that are space-filling and constrained by a few guiding biological principles. We devise a numerical method that enables the investigation of space-filling strategies and determination of which biological principles influence network structure. Optimization for only a single principle creates unrealistic networks that represent an extreme limit of the possible structures that could be observed in nature. We first study these extreme limits for two competing principles, minimal total material and minimal path lengths. We combine these two principles and enforce various thresholds for balance in the network hierarchy, which provides a novel approach that highlights the tradeoffs faced by biological networks and yields predictions that better match our empirical data. PMID:27415278

  1. Asymmetries arising from the space-filling nature of vascular networks

    NASA Astrophysics Data System (ADS)

    Hunt, David; Savage, Van

    Cardiovascular networks span the body by branching across many generations of vessels. The structural features of the network that accomplish this density and ubiquity of capillaries are often called space-filling. Some strategies do not lead to biologically adaptive structures, requiring too much construction material or space, delivering resources too slowly, or using too much power to move blood through the system. We empirically measure the structure of real networks to compare with predictions of model networks that are space-filling and constrained by a few guiding biological principles. We devise a numerical method that enables the investigation of space-filling strategies and determination of which biological principles influence network structure. Optimization for only a single principle creates unrealistic networks that represent an extreme limit of the possible structures that could be observed in nature. We first study these extreme limits for two competing principles, minimal total material and minimal path lengths. We combine these two principles and enforce various thresholds for balance in the network hierarchy, which provides a novel approach that highlights the trade-offs faced by biological networks and yields predictions that better match empirical data.

  2. Asymmetries arising from the space-filling nature of vascular networks.

    PubMed

    Hunt, David; Savage, Van M

    2016-06-01

    Cardiovascular networks span the body by branching across many generations of vessels. The resulting structure delivers blood over long distances to supply all cells with oxygen via the relatively short-range process of diffusion at the capillary level. The structural features of the network that accomplish this density and ubiquity of capillaries are often called space-filling. There are multiple strategies to fill a space, but some strategies do not lead to biologically adaptive structures by requiring too much construction material or space, delivering resources too slowly, or using too much power to move blood through the system. We empirically measure the structure of real networks (18 humans and 1 mouse) and compare these observations with predictions of model networks that are space-filling and constrained by a few guiding biological principles. We devise a numerical method that enables the investigation of space-filling strategies and determination of which biological principles influence network structure. Optimization for only a single principle creates unrealistic networks that represent an extreme limit of the possible structures that could be observed in nature. We first study these extreme limits for two competing principles, minimal total material and minimal path lengths. We combine these two principles and enforce various thresholds for balance in the network hierarchy, which provides a novel approach that highlights the tradeoffs faced by biological networks and yields predictions that better match our empirical data.

  3. Asymmetries arising from the space-filling nature of vascular networks

    NASA Astrophysics Data System (ADS)

    Hunt, David; Savage, Van M.

    2016-06-01

    Cardiovascular networks span the body by branching across many generations of vessels. The resulting structure delivers blood over long distances to supply all cells with oxygen via the relatively short-range process of diffusion at the capillary level. The structural features of the network that accomplish this density and ubiquity of capillaries are often called space-filling. There are multiple strategies to fill a space, but some strategies do not lead to biologically adaptive structures by requiring too much construction material or space, delivering resources too slowly, or using too much power to move blood through the system. We empirically measure the structure of real networks (18 humans and 1 mouse) and compare these observations with predictions of model networks that are space-filling and constrained by a few guiding biological principles. We devise a numerical method that enables the investigation of space-filling strategies and determination of which biological principles influence network structure. Optimization for only a single principle creates unrealistic networks that represent an extreme limit of the possible structures that could be observed in nature. We first study these extreme limits for two competing principles, minimal total material and minimal path lengths. We combine these two principles and enforce various thresholds for balance in the network hierarchy, which provides a novel approach that highlights the tradeoffs faced by biological networks and yields predictions that better match our empirical data.

  4. 2-Arachidonylglyceryl ether and abnormal cannabidiol-induced vascular smooth muscle relaxation in rabbit pulmonary arteries via receptor-pertussis toxin sensitive G proteins-ERK1/2 signaling.

    PubMed

    Su, Judy Y; Vo, Anhkiet C

    2007-03-22

    The receptor(s) used by cannabinoids to relax vascular smooth muscle is unknown. Here, we investigated the effects of 2-arachidonylglyceryl ether (2-AG ether), a metabolically stable endocannabinoid, and abnormal cannabidiol (abn-CBD) on relaxation of permeabilized pulmonary arterial strips monitored with force, and on extracellular signal-regulated mitogen-activated protein kinases (ERK1/2) phosphorylation in permeabilized vascular smooth muscle cells using immunoblotting. We found that 2-AG ether and abn-CBD caused relaxation and increased phosphorylation of ERK1/2. 2-AG ether effects were completely abolished by N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251), and N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716A), and partially blocked by (-)-1.3-dimethoxy-2-(3-3,4-trans-p-menthadien-(1,8)-yl)-orcinol (O-1918). In contrast, abn-CBD effects were completely abolished by O-1918, and only partially blocked by AM251, and SR141716A. Both 2-AG ether and abn-CBD effects were partially blocked by pertussis toxin, an inhibitor of Gi/o proteins. PD98059, an inhibitor of mitogen activated protein kinase kinase (MEK), completely abolished the relaxation, but only partially blocked the increased phosphorylation of ERK1/2 by 2-AG ether. In contrast, abn-CBD-induced relaxation was partially blocked and the increased phosphorylation of ERK1/2 was abolished by PD98059. These findings suggest that 2-AG ether and abn-CBD-induced vascular smooth muscle relaxation are mediated by the cannabinoid CB1 receptor, and the abn-CBD receptor, respectively, and are modulated by cross-talk between the receptors. These responses occur mainly by coupling to pertussis toxin sensitive G proteins, but also, in part independent of these G proteins, which have been classically thought to initiate MEK/ERK1/2 signaling to relax vascular smooth muscle.

  5. Suppression of vascular network formation by chronic hypoxia and prolyl-hydroxylase 2 (phd2) deficiency during vertebrate development.

    PubMed

    Metikala, Sanjeeva; Neuhaus, Herbert; Hollemann, Thomas

    2016-04-01

    In the adult, new vessels and red blood cells form in response to hypoxia. Here, the oxygen-sensing system (PHD-HIF) has recently been put into focus, since the prolyl-hydroxylase domain proteins (PHD) and hypoxia-inducible factors (HIF) are considered as potential therapeutic targets to treat ischemia, cancers or age-related macula degeneration. While the oxygen-sensing system (PHD-HIF) has been studied intensively in this respect, only little is known from developing vertebrate embryos since mutations within this pathway led to an early decease of embryos due to placental defects. During vertebrate embryogenesis, a progenitor cell called hemangioblast is assumed to give rise to blood cells and blood vessels in a process called hematopoiesis and vasculogenesis, respectively. Xenopus provides an ideal experimental system to address these processes in vivo, as its development does not depend on a functional placenta and thus allows analyzing the role of oxygen directly. To this end, we adopted a computer-controlled four-channel system, which allowed us to culture Xenopus embryos under defined oxygen concentrations. Our data show that the development of vascular structures and blood cells is strongly impaired under hypoxia, while general development is less compromised. Interestingly, suppression of Phd2 function using specific antisense morpholinos or a chemical inhibitor resulted in mostly overlapping vascular defects; nevertheless, blood cell was formed almost normally. Our results provide the first evidence that oxygen via Phd2 has a decisive influence on the formation of the vascular network during vertebrate embryogenesis. These findings may be considered in certain potential treatment concepts. PMID:26678600

  6. Sertoli Cells Modulate Testicular Vascular Network Development, Structure, and Function to Influence Circulating Testosterone Concentrations in Adult Male Mice

    PubMed Central

    Rebourcet, Diane; Wu, Junxi; Cruickshanks, Lyndsey; Smith, Sarah E.; Milne, Laura; Fernando, Anuruddika; Wallace, Robert J.; Gray, Calum D.; Hadoke, Patrick W. F.; Mitchell, Rod T.; O'Shaughnessy, Peter J.

    2016-01-01

    The testicular vasculature forms a complex network, providing oxygenation, micronutrients, and waste clearance from the testis. The vasculature is also instrumental to testis function because it is both the route by which gonadotropins are delivered to the testis and by which T is transported away to target organs. Whether Sertoli cells play a role in regulating the testicular vasculature in postnatal life has never been unequivocally demonstrated. In this study we used models of acute Sertoli cell ablation and acute germ cell ablation to address whether Sertoli cells actively influence vascular structure and function in the adult testis. Our findings suggest that Sertoli cells play a key role in supporting the structure of the testicular vasculature. Ablating Sertoli cells (and germ cells) or germ cells alone results in a similar reduction in testis size, yet only the specific loss of Sertoli cells leads to a reduction in total intratesticular vascular volume, the number of vascular branches, and the numbers of small microvessels; loss of germ cells alone has no effect on the testicular vasculature. These perturbations to the testicular vasculature leads to a reduction in fluid exchange between the vasculature and testicular interstitium, which reduces gonadotropin-stimulated circulating T concentrations, indicative of reduced Leydig cell stimulation and/or reduced secretion of T into the vasculature. These findings describe a new paradigm by which the transport of hormones and other factors into and out of the testis may be influenced by Sertoli cells and highlights these cells as potential targets for enhancing this endocrine relationship. PMID:27145015

  7. [Bone metabolism and cardiovascular function update. Inter-communication between bone marrow hematopoiesis and skeletal/vascular network].

    PubMed

    Katayama, Yoshio

    2014-07-01

    The hematopoiesis takes place in the bone marrow. Because bone marrow is the "marrow" of the bone, bone marrow does not exist without bone. The specialized microenvironment for hematopoietic stem cells (HSCs) to be appropriately functional is called "niche" . In the recent ten years since the bone-forming osteoblast was identified as a HSC niche, the entire mesenchymal lineage cells from mesenchymal stem cells to end-terminal osteocytes have been recognized as niche cells or niche-modulators. Among these, mesenchymal stem/progenitor cells are located at perivascular area. The very recent study showed the difference between arteriolar and sinusoidal niches. It is likely that the vascular network and the bone tissue are connected by the mesenchymal lineage cells as a complex of bone forming system, and HSCs utilize this complex as a series of niche.

  8. Particle-based simulation of ellipse-shaped particle aggregation as a model for vascular network formation

    NASA Astrophysics Data System (ADS)

    Palachanis, Dimitrios; Szabó, András; Merks, Roeland M. H.

    2015-12-01

    Computational modeling is helpful for elucidating the cellular mechanisms driving biological morphogenesis. Previous simulation studies of blood vessel growth based on the cellular Potts model proposed that elongated, adhesive or mutually attractive endothelial cells suffice for the formation of blood vessel sprouts and vascular networks. Because each mathematical representation of a model introduces potential artifacts, it is important that model results are reproduced using alternative modeling paradigms. Here, we present a lattice-free, particle-based simulation of the cell elongation model of vasculogenesis. The new, particle-based simulations confirm the results obtained from the previous cellular Potts simulations. Furthermore, our current findings suggest that the emergence of order is possible with the application of a high enough attractive force or, alternatively, a longer attraction radius. The methodology will be applicable to a range of problems in morphogenesis and noisy particle aggregation in which cell shape is a key determining factor.

  9. Vascular networks due to dynamically arrested crystalline ordering of elongated cells

    NASA Astrophysics Data System (ADS)

    Palm, Margriet M.; Merks, Roeland M. H.

    2013-01-01

    Recent experimental and theoretical studies suggest that crystallization and glass-like solidification are useful analogies for understanding cell ordering in confluent biological tissues. It remains unexplored how cellular ordering contributes to pattern formation during morphogenesis. With a computational model we show that a system of elongated, cohering biological cells can get dynamically arrested in a network pattern. Our model provides an explanation for the formation of cellular networks in culture systems that exclude intercellular interaction via chemotaxis or mechanical traction.

  10. Decreased C-reactive protein induces abnormal vascular structure in a rat model of liver dysfunction induced by bile duct ligation

    PubMed Central

    Jun, Ji Hye; Choi, Jong Ho; Bae, Si Hyun; Oh, Seh Hoon; Kim, Gi Jin

    2016-01-01

    Background/Aims Chronic liver disease leads to liver fibrosis, and although the liver does have a certain regenerative capacity, this disease is associated with dysfunction of the liver vessels. C-reactive protein (CRP) is produced in the liver and circulated from there for metabolism. CRP was recently shown to inhibit angiogenesis by inducing endothelial cell dysfunction. The objective of this study was to determine the effect of CRP levels on angiogenesis in a rat model of liver dysfunction induced by bile duct ligation (BDL). Methods The diameter of the hepatic vein was analyzed in rat liver tissues using hematoxylin and eosin (H&E) staining. The expression levels of angiogenic factors, albumin, and CRP were analyzed by real-time PCR and Western blotting. A tube formation assay was performed to confirm the effect of CRP on angiogenesis in human umbilical vein endothelial cells (HUVECs) treated with lithocholic acid (LCA) and siRNA-CRP. Results The diameter of the hepatic portal vein increased significantly with the progression of cirrhosis. The expression levels of angiogenic factors were increased in the cirrhotic liver. In contrast, the expression levels of albumin and CRP were significantly lower in the liver tissue obtained from the BDL rat model than in the normal liver. The CRP level was correlated with the expression of albumin in hepatocytes treated with LCA and siRNA-CRP. Tube formation was significantly decreased in HUVECs when they were treated with LCA or a combination of LCA and siRNA-CRP. Conclusion CRP seems to be involved in the abnormal formation of vessels in hepatic disease, and so it could be a useful diagnostic marker for hepatic disease. PMID:27729629

  11. Vascular progenitor cells isolated from human embryonic stem cells give rise to endothelial and smooth muscle like cells and form vascular networks in vivo.

    PubMed

    Ferreira, Lino S; Gerecht, Sharon; Shieh, Hester F; Watson, Nicki; Rupnick, Maria A; Dallabrida, Susan M; Vunjak-Novakovic, Gordana; Langer, Robert

    2007-08-01

    We report that human embryonic stem cells contain a population of vascular progenitor cells that have the ability to differentiate into endothelial-like and smooth muscle (SM)-like cells. Vascular progenitor cells were isolated from EBs grown in suspension for 10 days and were characterized by expression of the endothelial/hematopoietic marker CD34 (CD34+ cells). When these cells are subsequently cultured in EGM-2 (endothelial growth medium) supplemented with vascular endothelial growth factor-165 (50 ng/mL), they give rise to endothelial-like cells characterized by a cobblestone cell morphology, expression of endothelial markers (platelet endothelial cell-adhesion molecule-1, CD34, KDR/Flk-1, vascular endothelial cadherin, von Willebrand factor), incorporation of acetylated low-density lipoprotein, and formation of capillary-like structures when placed in Matrigel. In contrast, when CD34+ cells are cultured in EGM-2 supplemented with platelet-derived growth factor-BB (50 ng/mL), they give rise to SM-like cells characterized by spindle-shape morphology, expression of SM cell markers (alpha-SM actin, SM myosin heavy chain, calponin, caldesmon, SM alpha-22), and the ability to contract and relax in response to common pharmacological agents such as carbachol and atropine but rarely form capillary-like structures when placed in Matrigel. Implantation studies in nude mice show that both cell types contribute to the formation of human microvasculature. Some microvessels contained mouse blood cells, which indicates functional integration with host vasculature. Therefore, the vascular progenitors isolated from human embryonic stem cells using methods established in the present study could provide a means to examine the mechanisms of endothelial and SM cell development, and they could also provide a potential source of cells for vascular tissue engineering.

  12. Simultaneous submicrometric 3D imaging of the micro-vascular network and the neuronal system in a mouse spinal cord

    PubMed Central

    Fratini, Michela; Bukreeva, Inna; Campi, Gaetano; Brun, Francesco; Tromba, Giuliana; Modregger, Peter; Bucci, Domenico; Battaglia, Giuseppe; Spanò, Raffaele; Mastrogiacomo, Maddalena; Requardt, Herwig; Giove, Federico; Bravin, Alberto; Cedola, Alessia

    2015-01-01

    Faults in vascular (VN) and neuronal networks of spinal cord are responsible for serious neurodegenerative pathologies. Because of inadequate investigation tools, the lacking knowledge of the complete fine structure of VN and neuronal system represents a crucial problem. Conventional 2D imaging yields incomplete spatial coverage leading to possible data misinterpretation, whereas standard 3D computed tomography imaging achieves insufficient resolution and contrast. We show that X-ray high-resolution phase-contrast tomography allows the simultaneous visualization of three-dimensional VN and neuronal systems of ex-vivo mouse spinal cord at scales spanning from millimeters to hundreds of nanometers, with nor contrast agent nor sectioning and neither destructive sample-preparation. We image both the 3D distribution of micro-capillary network and the micrometric nerve fibers, axon-bundles and neuron soma. Our approach is very suitable for pre-clinical investigation of neurodegenerative pathologies and spinal-cord-injuries, in particular to resolve the entangled relationship between VN and neuronal system. PMID:25686728

  13. Simultaneous submicrometric 3D imaging of the micro-vascular network and the neuronal system in a mouse spinal cord

    NASA Astrophysics Data System (ADS)

    Fratini, Michela; Bukreeva, Inna; Campi, Gaetano; Brun, Francesco; Tromba, Giuliana; Modregger, Peter; Bucci, Domenico; Battaglia, Giuseppe; Spanò, Raffaele; Mastrogiacomo, Maddalena; Requardt, Herwig; Giove, Federico; Bravin, Alberto; Cedola, Alessia

    2015-02-01

    Faults in vascular (VN) and neuronal networks of spinal cord are responsible for serious neurodegenerative pathologies. Because of inadequate investigation tools, the lacking knowledge of the complete fine structure of VN and neuronal system represents a crucial problem. Conventional 2D imaging yields incomplete spatial coverage leading to possible data misinterpretation, whereas standard 3D computed tomography imaging achieves insufficient resolution and contrast. We show that X-ray high-resolution phase-contrast tomography allows the simultaneous visualization of three-dimensional VN and neuronal systems of ex-vivo mouse spinal cord at scales spanning from millimeters to hundreds of nanometers, with nor contrast agent nor sectioning and neither destructive sample-preparation. We image both the 3D distribution of micro-capillary network and the micrometric nerve fibers, axon-bundles and neuron soma. Our approach is very suitable for pre-clinical investigation of neurodegenerative pathologies and spinal-cord-injuries, in particular to resolve the entangled relationship between VN and neuronal system.

  14. Meiotic abnormalities

    SciTech Connect

    1993-12-31

    Chapter 19, describes meiotic abnormalities. These include nondisjunction of autosomes and sex chromosomes, genetic and environmental causes of nondisjunction, misdivision of the centromere, chromosomally abnormal human sperm, male infertility, parental age, and origin of diploid gametes. 57 refs., 2 figs., 1 tab.

  15. Automated method for the identification and analysis of vascular tree structures in retinal vessel network

    NASA Astrophysics Data System (ADS)

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

    2011-03-01

    Structural analysis of retinal vessel network has so far served in the diagnosis of retinopathies and systemic diseases. The retinopathies are known to affect the morphologic properties of retinal vessels such as course, shape, caliber, and tortuosity. Whether the arteries and the veins respond to these changes together or in tandem has always been a topic of discussion. However the diseases such as diabetic retinopathy and retinopathy of prematurity have been diagnosed with the morphologic changes specific either to arteries or to veins. Thus a method describing the separation of retinal vessel trees imaged in a two dimensional color fundus image may assist in artery-vein classification and quantitative assessment of morphologic changes particular to arteries or veins. We propose a method based on mathematical morphology and graph search to identify and label the retinal vessel trees, which provides a structural mapping of vessel network in terms of each individual primary vessel, its branches and spatial positions of branching and cross-over points. The method was evaluated on a dataset of 15 fundus images resulting into an accuracy of 92.87 % correctly assigned vessel pixels when compared with the manual labeling of separated vessel trees. Accordingly, the structural mapping method performs well and we are currently investigating its potential in evaluating the characteristic properties specific to arteries or veins.

  16. DWI and complex brain network analysis predicts vascular cognitive impairment in spontaneous hypertensive rats undergoing executive function tests

    PubMed Central

    López-Gil, Xavier; Amat-Roldan, Iván; Tudela, Raúl; Castañé, Anna; Prats-Galino, Alberto; Planas, Anna M.; Farr, Tracy D.; Soria, Guadalupe

    2014-01-01

    The identification of biomarkers of vascular cognitive impairment is urgent for its early diagnosis. The aim of this study was to detect and monitor changes in brain structure and connectivity, and to correlate them with the decline in executive function. We examined the feasibility of early diagnostic magnetic resonance imaging (MRI) to predict cognitive impairment before onset in an animal model of chronic hypertension: Spontaneously Hypertensive Rats. Cognitive performance was tested in an operant conditioning paradigm that evaluated learning, memory, and behavioral flexibility skills. Behavioral tests were coupled with longitudinal diffusion weighted imaging acquired with 126 diffusion gradient directions and 0.3 mm3 isometric resolution at 10, 14, 18, 22, 26, and 40 weeks after birth. Diffusion weighted imaging was analyzed in two different ways, by regional characterization of diffusion tensor imaging (DTI) indices, and by assessing changes in structural brain network organization based on Q-Ball tractography. Already at the first evaluated times, DTI scalar maps revealed significant differences in many regions, suggesting loss of integrity in white and gray matter of spontaneously hypertensive rats when compared to normotensive control rats. In addition, graph theory analysis of the structural brain network demonstrated a significant decrease of hierarchical modularity, global and local efficacy, with predictive value as shown by regional three-fold cross validation study. Moreover, these decreases were significantly correlated with the behavioral performance deficits observed at subsequent time points, suggesting that the diffusion weighted imaging and connectivity studies can unravel neuroimaging alterations even overt signs of cognitive impairment become apparent. PMID:25100993

  17. Default mode network and frontolimbic gray matter abnormalities in patients with borderline personality disorder: A voxel-based meta-analysis

    PubMed Central

    Yang, Xun; Hu, Liyuan; Zeng, Jianguang; Tan, Ying; Cheng, Bochao

    2016-01-01

    Specific frontolimbic abnormalities are hypothesized to underlie the etiology of borderline personality disorder (BPD). However, findings from neuroimaging studies were inconsistent. In the current study, we aimed to provide a complete overview of cerebral microstructural alterations in gray matter (GM) of BPD patients. A total of 11 studies were enrolled, comprising 275 BPD patients and 290 healthy controls (HCs). A meta-analysis was conduct to quantitatively estimate regional GM abnormalities in BPD patients using the seed-based d mapping (SDM). Meta-regression was also conducted. Compared with HCs, the BPD patients exhibited increased GM mainly in bilateral supplementary motor area extending to right posterior cingulated cortex (PCC) and bilateral primary motor cortex, right middle frontal gyrus (MFG), and the bilateral precuneus extending to bilateral PCC. Decreased GM was identified in bilateral middle temporal gyri, right inferior frontal gyrus extending to right insular, left hippocampus and left superior frontal gyrus extending to left medial orbitofrontal cortex. The mean age of BPD patients were found nagativly associated with GM alterations in right MFG. Our findings suggested that BPD patients have significantly GM abnormalities in the default mode network and frontolimbic circuit. Our results provided further evidences in elucidating the underline neural mechanisms of BPD. PMID:27694955

  18. Vascular Lesions.

    PubMed

    Jahnke, Marla N

    2016-08-01

    Vascular lesions in childhood are comprised of vascular tumors and vascular malformations. Vascular tumors encompass neoplasms of the vascular system, of which infantile hemangiomas (IHs) are the most common. Vascular malformations, on the other hand, consist of lesions due to anomalous development of the vascular system, including the capillary, venous, arterial, and lymphatic systems. Capillary malformations represent the most frequent type of vascular malformation. IHs and vascular malformations tend to follow relatively predictable growth patterns in that IHs grow then involute during early childhood, whereas vascular malformations tend to exhibit little change. Both vascular tumors and vascular malformations can demonstrate a wide range of severity and potential associated complications necessitating specialist intervention when appropriate. Evaluation and treatment of the most common types of vascular lesions are discussed in this article. [Pediatr Ann. 2016;45(8):e299-e305.]. PMID:27517358

  19. Craniofacial Abnormalities

    MedlinePlus

    ... of the skull and face. Craniofacial abnormalities are birth defects of the face or head. Some, like cleft ... palate, are among the most common of all birth defects. Others are very rare. Most of them affect ...

  20. Chromosome Abnormalities

    MedlinePlus

    ... decade, newer techniques have been developed that allow scientists and doctors to screen for chromosomal abnormalities without using a microscope. These newer methods compare the patient's DNA to a normal DNA ...

  1. Walking abnormalities

    MedlinePlus

    ... include: Arthritis of the leg or foot joints Conversion disorder (a psychological disorder) Foot problems (such as a ... injuries. For an abnormal gait that occurs with conversion disorder, counseling and support from family members are strongly ...

  2. Nail abnormalities

    MedlinePlus

    Beau's lines; Fingernail abnormalities; Spoon nails; Onycholysis; Leukonychia; Koilonychia; Brittle nails ... Just like the skin, the fingernails tell a lot about your health: ... the fingernail. These lines can occur after illness, injury to ...

  3. Maintenance of xylem Network Transport Capacity: A Review of Embolism Repair in Vascular Plants

    PubMed Central

    Brodersen, Craig R.; McElrone, Andrew J.

    2013-01-01

    Maintenance of long distance water transport in xylem is essential to plant health and productivity. Both biotic and abiotic environmental conditions lead to embolism formation within the xylem resulting in lost transport capacity and ultimately death. Plants exhibit a variety of strategies to either prevent or restore hydraulic capacity through cavitation resistance with specialized anatomy, replacement of compromised conduits with new growth, and a metabolically active embolism repair mechanism. In recent years, mounting evidence suggests that metabolically active cells surrounding the xylem conduits in some, but not all, species are capable of restoring hydraulic conductivity. This review summarizes our current understanding of the osmotically driven embolism repair mechanism, the known genetic and anatomical components related to embolism repair, rehydration pathways through the xylem, and the role of capacitance. Anatomical differences between functional plant groups may be one of the limiting factors that allow some plants to refill while others do not, but further investigations are necessary to fully understand this dynamic process. Finally, xylem networks should no longer be considered an assemblage of dead, empty conduits, but instead a metabolically active tissue finely tuned to respond to ever changing environmental cues. PMID:23630539

  4. Vascular Cures

    MedlinePlus

    ... Malformation Atherosclerosis Buerger's Disease Carotid Artery Disease Chronic Venous Insufficiency Congenital Vascular Malformation Critical Limb Ischemia (CLI) Deep Vein Thrombosis (DVT) Diabetes and Vascular Disease Fibromuscular Dysplasia High ...

  5. Enlarged parietal foramina: a rare finding in a female Greek skull with unusual multiple Wormian bones and a rich parietal vascular network.

    PubMed

    Piagkou, Maria; Skotsimara, Georgia; Repousi, Elpida; Paraskevas, George; Natsis, Konstantinos

    2013-06-01

    Enlarged parietal foramina (>5 mm) is an extremely rare developmental defect of the parietal bone, which is distinguished from the normal small parietal foramina, as genes associated with this entity have been identified, suggesting that it is hereditary in nature. We describe a dry skull of a 35-year-old female, with enlarged parietal foramina symmetrically situated bilaterally, oval in shape, measuring 4.5 × 9.3 mm (right) and 4.9 × 9.2 mm (left) in size. The foramina coexisted with multiple Wormian bones in several sites of the skull. On the inner parietal bone surface, the anterior, posterior and lateral foramina's rims carried grooves, which were continuous with the middle meningeal vessels' branches, indicating that a rich vascular network existed around the foramina. These vascular grooves also notched the external table at the margin of the foramina, which suggests a potential communication between the meningeal and the scalp vessels. In addition, this vascular variation should be taken into consideration when performing surgical interventions in the area, because the large vascular supply to the foramina is a possible source of extensive bleeding. Moreover, the interaction of intracranial and extracranial veins and the fact that the blood flows in them in both directions, as they are valveless, could represent a possible pathway for infections to spread in the cranial cavity.

  6. Neurofilament light polypeptide gene N98S mutation in mice leads to neurofilament network abnormalities and a Charcot-Marie-Tooth Type 2E phenotype.

    PubMed

    Adebola, Adijat A; Di Castri, Theo; He, Chui-Zhen; Salvatierra, Laura A; Zhao, Jian; Brown, Kristy; Lin, Chyuan-Sheng; Worman, Howard J; Liem, Ronald K H

    2015-04-15

    Charcot-Marie-Tooth disease (CMT) is the most commonly inherited neurological disorder with a prevalence of 1 in 2500 people worldwide. Patients suffer from degeneration of the peripheral nerves that control sensory information of the foot/leg and hand/arm. Multiple mutations in the neurofilament light polypeptide gene, NEFL, cause CMT2E. Previous studies in transfected cells showed that expression of disease-associated neurofilament light chain variants results in abnormal intermediate filament networks associated with defects in axonal transport. We have now generated knock-in mice with two different point mutations in Nefl: P8R that has been reported in multiple families with variable age of onset and N98S that has been described as an early-onset, sporadic mutation in multiple individuals. Nefl(P8R/+) and Nefl(P8R/P8R) mice were indistinguishable from Nefl(+/+) in terms of behavioral phenotype. In contrast, Nefl(N98S/+) mice had a noticeable tremor, and most animals showed a hindlimb clasping phenotype. Immunohistochemical analysis revealed multiple inclusions in the cell bodies and proximal axons of spinal cord neurons, disorganized processes in the cerebellum and abnormal processes in the cerebral cortex and pons. Abnormal processes were observed as early as post-natal day 7. Electron microscopic analysis of sciatic nerves showed a reduction in the number of neurofilaments, an increase in the number of microtubules and a decrease in the axonal diameters. The Nefl(N98S/+) mice provide an excellent model to study the pathogenesis of CMT2E and should prove useful for testing potential therapies.

  7. A voxel-based morphometry (VBM) analysis of regional grey and white matter volume abnormalities within the speech production network of children who stutter

    PubMed Central

    Beal, Deryk S.; Gracco, Vincent L.; Brettschneider, Jane; Kroll, Robert M.; De Nil, Luc F.

    2012-01-01

    It is well documented that neuroanatomical differences exist between adults who stutter and their fluently speaking peers. Specifically, adults who stutter have been found to have more grey matter volume (GMV) in speech relevant regions including inferior frontal gyrus, insula and superior temporal gyrus (Beal et al., 2007; Song et al., 2007). Despite stuttering having its onset in childhood only one study has investigated the neuroanatomical differences between children who do and do not stutter. Chang et al. (2008) reported children who stutter had less GMV in the bilateral inferior frontal gyri and middle temporal gyrus relative to fluently speaking children. Thus it appears that children who stutter present with unique neuroanatomical abnormalities as compared to those of adults who stutter. In order to better understand the neuroanatomical correlates of stuttering earlier in its development, near the time of onset, we used voxel-based morphometry to examine volumetric differences between 11 children who stutter and 11 fluent children. Children who stutter had less GMV in the bilateral inferior frontal gyri and left putamen but more GMV in right Rolandic operculum and superior temporal gyrus relative to fluent children. Children who stutter also had less white matter volume bilaterally in the forceps minor of the corpus callosum. We discuss our findings of widespread anatomic abnormalities throughout the cortical network for speech motor control within the context of the speech motor skill limitations identified in people who stutter (Namasivayam and van Lieshout, 2008; Smits-Bandstra et al., 2006). PMID:23140891

  8. Cocaine addiction related reproducible brain regions of abnormal default-mode network functional connectivity: a group ICA study with different model orders.

    PubMed

    Ding, Xiaoyu; Lee, Seong-Whan

    2013-08-26

    Model order selection in group independent component analysis (ICA) has a significant effect on the obtained components. This study investigated the reproducible brain regions of abnormal default-mode network (DMN) functional connectivity related with cocaine addiction through different model order settings in group ICA. Resting-state fMRI data from 24 cocaine addicts and 24 healthy controls were temporally concatenated and processed by group ICA using model orders of 10, 20, 30, 40, and 50, respectively. For each model order, the group ICA approach was repeated 100 times using the ICASSO toolbox and after clustering the obtained components, centrotype-based anterior and posterior DMN components were selected for further analysis. Individual DMN components were obtained through back-reconstruction and converted to z-score maps. A whole brain mixed effects factorial ANOVA was performed to explore the differences in resting-state DMN functional connectivity between cocaine addicts and healthy controls. The hippocampus, which showed decreased functional connectivity in cocaine addicts for all the tested model orders, might be considered as a reproducible abnormal region in DMN associated with cocaine addiction. This finding suggests that using group ICA to examine the functional connectivity of the hippocampus in the resting-state DMN may provide an additional insight potentially relevant for cocaine-related diagnoses and treatments. PMID:23707901

  9. Ultrastructure of blood and lymphatic vascular networks in three-dimensional cultured tissues fabricated by extracellular matrix nanofilm-based cell accumulation technique.

    PubMed

    Asano, Yoshiya; Nishiguchi, Akihiro; Matsusaki, Michiya; Okano, Daisuke; Saito, Erina; Akashi, Mitsuru; Shimoda, Hiroshi

    2014-06-01

    Cell accumulation technique is an extracellular matrix (ECM) nanofilm-based tissue-constructing method that enables formation of multilayered hybrid culture tissues. In this method, ECM-nanofilm is constructed using layer-by-layer assembly of fibronectin and gelatin on culture cells. The ECM-nanofilm promotes cell-to-cell interaction; then the three-dimensional (3D) multilayered tissue can be constructed with morphological change of the cells mimicking living tissues. By using this method, we have successfully produced tubular networks of human umbilical venous endothelial cells (HUVECs) and human dermal lymphatic endothelial cells (HDLECs) in 3D multilayered normal human dermal fibroblasts (NHDFs). This study demonstrated morphological characteristics of the vascular networks in the engineered tissues by using light and electron microscopy. In light microscopy, HUVECs and HDLECs formed luminal structures such as native blood and lymphatic capillaries, respectively. Electron microscopy showed distinct ultrastructural aspects of the vasculature of HUVECs or HDLECs with intermediated NHDFs and abundant ECM. The vasculature constructed by HUVECs exhibited structures similar to native blood capillaries, involving overlapping endothelial connections with adherens junctions, abundant vesicles in the endothelial cells and basement membrane-like structure. The detection of laminin around HUVEC-constructed vessels supported the presence of perivascular basal lamina. The vasculature constructed by HDLECs showed some ultrastructural characteristics similar to those of native lymphatic capillaries such as irregular vascular shape, loose adhesive connection and gap formation between endothelial cells. In conclusion, our novel vascular network models fabricated by the cell accumulation technique provide highly organized blood and lymphatic capillary networks mimicking the vasculatures in vivo.

  10. Theory of mind mediates the prospective relationship between abnormal social brain network morphology and chronic behavior problems after pediatric traumatic brain injury.

    PubMed

    Ryan, Nicholas P; Catroppa, Cathy; Beare, Richard; Silk, Timothy J; Crossley, Louise; Beauchamp, Miriam H; Yeates, Keith Owen; Anderson, Vicki A

    2016-04-01

    Childhood and adolescence coincide with rapid maturation and synaptic reorganization of distributed neural networks that underlie complex cognitive-affective behaviors. These regions, referred to collectively as the 'social brain network' (SBN) are commonly vulnerable to disruption from pediatric traumatic brain injury (TBI); however, the mechanisms that link morphological changes in the SBN to behavior problems in this population remain unclear. In 98 children and adolescents with mild to severe TBI, we acquired 3D T1-weighted MRIs at 2-8 weeks post-injury. For comparison, 33 typically developing controls of similar age, sex and education were scanned. All participants were assessed on measures of Theory of Mind (ToM) at 6 months post-injury and parents provided ratings of behavior problems at 24-months post-injury. Severe TBI was associated with volumetric reductions in the overall SBN package, as well as regional gray matter structural change in multiple component regions of the SBN. When compared with TD controls and children with milder injuries, the severe TBI group had significantly poorer ToM, which was associated with more frequent behavior problems and abnormal SBN morphology. Mediation analysis indicated that impaired theory of mind mediated the prospective relationship between abnormal SBN morphology and more frequent chronic behavior problems. Our findings suggest that sub-acute alterations in SBN morphology indirectly contribute to long-term behavior problems via their influence on ToM. Volumetric change in the SBN and its putative hub regions may represent useful imaging biomarkers for prediction of post-acute social cognitive impairment, which may in turn elevate risk for chronic behavior problems.

  11. Theory of mind mediates the prospective relationship between abnormal social brain network morphology and chronic behavior problems after pediatric traumatic brain injury.

    PubMed

    Ryan, Nicholas P; Catroppa, Cathy; Beare, Richard; Silk, Timothy J; Crossley, Louise; Beauchamp, Miriam H; Yeates, Keith Owen; Anderson, Vicki A

    2016-04-01

    Childhood and adolescence coincide with rapid maturation and synaptic reorganization of distributed neural networks that underlie complex cognitive-affective behaviors. These regions, referred to collectively as the 'social brain network' (SBN) are commonly vulnerable to disruption from pediatric traumatic brain injury (TBI); however, the mechanisms that link morphological changes in the SBN to behavior problems in this population remain unclear. In 98 children and adolescents with mild to severe TBI, we acquired 3D T1-weighted MRIs at 2-8 weeks post-injury. For comparison, 33 typically developing controls of similar age, sex and education were scanned. All participants were assessed on measures of Theory of Mind (ToM) at 6 months post-injury and parents provided ratings of behavior problems at 24-months post-injury. Severe TBI was associated with volumetric reductions in the overall SBN package, as well as regional gray matter structural change in multiple component regions of the SBN. When compared with TD controls and children with milder injuries, the severe TBI group had significantly poorer ToM, which was associated with more frequent behavior problems and abnormal SBN morphology. Mediation analysis indicated that impaired theory of mind mediated the prospective relationship between abnormal SBN morphology and more frequent chronic behavior problems. Our findings suggest that sub-acute alterations in SBN morphology indirectly contribute to long-term behavior problems via their influence on ToM. Volumetric change in the SBN and its putative hub regions may represent useful imaging biomarkers for prediction of post-acute social cognitive impairment, which may in turn elevate risk for chronic behavior problems. PMID:26796967

  12. [Vascular parkinsonism].

    PubMed

    Marxreiter, F; Winkler, J

    2016-07-01

    Parkinsonism may result from cerebral vascular disorders that feature white matter lesions and small vessel pathology. Vascular Parkinsonism typically presents as lower body Parkinsonism with predominant gait impairment. Urinary incontinence and cognitive decline are additional features of the disease. There is a considerable overlap between vascular Parkinsonism and vascular dementia. We review the clinical characteristics of vascular Parkinsonism and discuss the current treatment approaches, as well as the role of brain imaging for the diagnostic workup. . PMID:27299942

  13. p73 is required for endothelial cell differentiation, migration and the formation of vascular networks regulating VEGF and TGFβ signaling

    PubMed Central

    Fernandez-Alonso, R; Martin-Lopez, M; Gonzalez-Cano, L; Garcia, S; Castrillo, F; Diez-Prieto, I; Fernandez-Corona, A; Lorenzo-Marcos, M E; Li, X; Claesson-Welsh, L; Marques, M M; Marin, M C

    2015-01-01

    Vasculogenesis, the establishment of the vascular plexus and angiogenesis, branching of new vessels from the preexisting vasculature, involves coordinated endothelial differentiation, proliferation and migration. Disturbances in these coordinated processes may accompany diseases such as cancer. We hypothesized that the p53 family member p73, which regulates cell differentiation in several contexts, may be important in vascular development. We demonstrate that p73 deficiency perturbed vascular development in the mouse retina, decreasing vascular branching, density and stability. Furthermore, p73 deficiency could affect non endothelial cells (ECs) resulting in reduced in vivo proangiogenic milieu. Moreover, p73 functional inhibition, as well as p73 deficiency, hindered vessel sprouting, tubulogenesis and the assembly of vascular structures in mouse embryonic stem cell and induced pluripotent stem cell cultures. Therefore, p73 is necessary for EC biology and vasculogenesis and, in particular, that DNp73 regulates EC migration and tube formation capacity by regulation of expression of pro-angiogenic factors such as transforming growth factor-β and vascular endothelial growth factors. DNp73 expression is upregulated in the tumor environment, resulting in enhanced angiogenic potential of B16-F10 melanoma cells. Our results demonstrate, by the first time, that differential p73-isoform regulation is necessary for physiological vasculogenesis and angiogenesis and DNp73 overexpression becomes a positive advantage for tumor progression due to its pro-angiogenic capacity. PMID:25571973

  14. p73 is required for endothelial cell differentiation, migration and the formation of vascular networks regulating VEGF and TGFβ signaling.

    PubMed

    Fernandez-Alonso, R; Martin-Lopez, M; Gonzalez-Cano, L; Garcia, S; Castrillo, F; Diez-Prieto, I; Fernandez-Corona, A; Lorenzo-Marcos, M E; Li, X; Claesson-Welsh, L; Marques, M M; Marin, M C

    2015-08-01

    Vasculogenesis, the establishment of the vascular plexus and angiogenesis, branching of new vessels from the preexisting vasculature, involves coordinated endothelial differentiation, proliferation and migration. Disturbances in these coordinated processes may accompany diseases such as cancer. We hypothesized that the p53 family member p73, which regulates cell differentiation in several contexts, may be important in vascular development. We demonstrate that p73 deficiency perturbed vascular development in the mouse retina, decreasing vascular branching, density and stability. Furthermore, p73 deficiency could affect non endothelial cells (ECs) resulting in reduced in vivo proangiogenic milieu. Moreover, p73 functional inhibition, as well as p73 deficiency, hindered vessel sprouting, tubulogenesis and the assembly of vascular structures in mouse embryonic stem cell and induced pluripotent stem cell cultures. Therefore, p73 is necessary for EC biology and vasculogenesis and, in particular, that DNp73 regulates EC migration and tube formation capacity by regulation of expression of pro-angiogenic factors such as transforming growth factor-β and vascular endothelial growth factors. DNp73 expression is upregulated in the tumor environment, resulting in enhanced angiogenic potential of B16-F10 melanoma cells. Our results demonstrate, by the first time, that differential p73-isoform regulation is necessary for physiological vasculogenesis and angiogenesis and DNp73 overexpression becomes a positive advantage for tumor progression due to its pro-angiogenic capacity.

  15. Abnormal Brain Activation in Neurofibromatosis Type 1: A Link between Visual Processing and the Default Mode Network

    PubMed Central

    Violante, Inês R.; Ribeiro, Maria J.; Cunha, Gil; Bernardino, Inês; Duarte, João V.; Ramos, Fabiana; Saraiva, Jorge; Silva, Eduardo; Castelo-Branco, Miguel

    2012-01-01

    Neurofibromatosis type 1 (NF1) is one of the most common single gene disorders affecting the human nervous system with a high incidence of cognitive deficits, particularly visuospatial. Nevertheless, neurophysiological alterations in low-level visual processing that could be relevant to explain the cognitive phenotype are poorly understood. Here we used functional magnetic resonance imaging (fMRI) to study early cortical visual pathways in children and adults with NF1. We employed two distinct stimulus types differing in contrast and spatial and temporal frequencies to evoke relatively different activation of the magnocellular (M) and parvocellular (P) pathways. Hemodynamic responses were investigated in retinotopically-defined regions V1, V2 and V3 and then over the acquired cortical volume. Relative to matched control subjects, patients with NF1 showed deficient activation of the low-level visual cortex to both stimulus types. Importantly, this finding was observed for children and adults with NF1, indicating that low-level visual processing deficits do not ameliorate with age. Moreover, only during M-biased stimulation patients with NF1 failed to deactivate or even activated anterior and posterior midline regions of the default mode network. The observation that the magnocellular visual pathway is impaired in NF1 in early visual processing and is specifically associated with a deficient deactivation of the default mode network may provide a neural explanation for high-order cognitive deficits present in NF1, particularly visuospatial and attentional. A link between magnocellular and default mode network processing may generalize to neuropsychiatric disorders where such deficits have been separately identified. PMID:22723888

  16. Structural vascular disease in Africans: Performance of ethnic-specific waist circumference cut points using logistic regression and neural network analyses: The SABPA study.

    PubMed

    Botha, J; de Ridder, J H; Potgieter, J C; Steyn, H S; Malan, L

    2013-10-01

    A recently proposed model for waist circumference cut points (RPWC), driven by increased blood pressure, was demonstrated in an African population. We therefore aimed to validate the RPWC by comparing the RPWC and the Joint Statement Consensus (JSC) models via Logistic Regression (LR) and Neural Networks (NN) analyses. Urban African gender groups (N=171) were stratified according to the JSC and RPWC cut point models. Ultrasound carotid intima media thickness (CIMT), blood pressure (BP) and fasting bloods (glucose, high density lipoprotein (HDL) and triglycerides) were obtained in a well-controlled setting. The RPWC male model (LR ROC AUC: 0.71, NN ROC AUC: 0.71) was practically equal to the JSC model (LR ROC AUC: 0.71, NN ROC AUC: 0.69) to predict structural vascular -disease. Similarly, the female RPWC model (LR ROC AUC: 0.84, NN ROC AUC: 0.82) and JSC model (LR ROC AUC: 0.82, NN ROC AUC: 0.81) equally predicted CIMT as surrogate marker for structural vascular disease. Odds ratios supported validity where prediction of CIMT revealed -clinical -significance, well over 1, for both the JSC and RPWC models in African males and females (OR 3.75-13.98). In conclusion, the proposed RPWC model was substantially validated utilizing linear and non-linear analyses. We therefore propose ethnic-specific WC cut points (African males, ≥90 cm; -females, ≥98 cm) to predict a surrogate marker for structural vascular disease.

  17. A voxel-based morphometry (VBM) analysis of regional grey and white matter volume abnormalities within the speech production network of children who stutter.

    PubMed

    Beal, Deryk S; Gracco, Vincent L; Brettschneider, Jane; Kroll, Robert M; De Nil, Luc F

    2013-09-01

    It is well documented that neuroanatomical differences exist between adults who stutter and their fluently speaking peers. Specifically, adults who stutter have been found to have more grey matter volume (GMV) in speech relevant regions including inferior frontal gyrus, insula and superior temporal gyrus (Beal et al., 2007; Song et al., 2007). Despite stuttering having its onset in childhood only one study has investigated the neuroanatomical differences between children who do and do not stutter. Chang et al. (2008) reported children who stutter had less GMV in the bilateral inferior frontal gyri and middle temporal gyrus relative to fluently speaking children. Thus it appears that children who stutter present with unique neuroanatomical abnormalities as compared to those of adults who stutter. In order to better understand the neuroanatomical correlates of stuttering earlier in its development, near the time of onset, we used voxel-based morphometry to examine volumetric differences between 11 children who stutter and 11 fluent children. Children who stutter had less GMV in the bilateral inferior frontal gyri and left putamen but more GMV in right Rolandic operculum and superior temporal gyrus relative to fluent children. Children who stutter also had less white matter volume bilaterally in the forceps minor of the corpus callosum. We discuss our findings of widespread anatomic abnormalities throughout the cortical network for speech motor control within the context of the speech motor skill limitations identified in people who stutter (Namasivayam and van Lieshout, 2008; Smits-Bandstra et al., 2006).

  18. Vascular ring

    MedlinePlus

    ... with aberrant subclavian and left ligamentum ateriosus; Congenital heart defect - vascular ring; Birth defect heart - vascular ring ... accounts for less than 1% of all congenital heart problems. The condition occurs as often in males ...

  19. Radiologic atlas of pulmonary abnormalities in children

    SciTech Connect

    Singleton, E.B.; Wagner, M.L.; Dutton, R.V.

    1988-01-01

    This book is an atlas about thoracic abnormalities in infants and children. The authors include computed tomographic, digital subtraction angiographic, ultrasonographic, and a few magnetic resonance (MR) images. They recognize and discuss how changes in the medical treatment of premature infants and the management of infection and pediatric tumors have altered some of the appearances and considerations in these diseases. Oriented toward all aspects of pulmonary abnormalities, the book starts with radiographic techniques and then discusses the normal chest, the newborn, infections, tumors, and pulmonary vascular diseases. There is comprehensive treatment of mediastinal abnormalities and a discussion of airway abnormalities.

  20. Anatomical Network Comparison of Human Upper and Lower, Newborn and Adult, and Normal and Abnormal Limbs, with Notes on Development, Pathology and Limb Serial Homology vs. Homoplasy

    PubMed Central

    Diogo, Rui; Esteve-Altava, Borja; Smith, Christopher; Boughner, Julia C.; Rasskin-Gutman, Diego

    2015-01-01

    How do the various anatomical parts (modules) of the animal body evolve into very different integrated forms (integration) yet still function properly without decreasing the individual’s survival? This long-standing question remains unanswered for multiple reasons, including lack of consensus about conceptual definitions and approaches, as well as a reasonable bias toward the study of hard tissues over soft tissues. A major difficulty concerns the non-trivial technical hurdles of addressing this problem, specifically the lack of quantitative tools to quantify and compare variation across multiple disparate anatomical parts and tissue types. In this paper we apply for the first time a powerful new quantitative tool, Anatomical Network Analysis (AnNA), to examine and compare in detail the musculoskeletal modularity and integration of normal and abnormal human upper and lower limbs. In contrast to other morphological methods, the strength of AnNA is that it allows efficient and direct empirical comparisons among body parts with even vastly different architectures (e.g. upper and lower limbs) and diverse or complex tissue composition (e.g. bones, cartilages and muscles), by quantifying the spatial organization of these parts—their topological patterns relative to each other—using tools borrowed from network theory. Our results reveal similarities between the skeletal networks of the normal newborn/adult upper limb vs. lower limb, with exception to the shoulder vs. pelvis. However, when muscles are included, the overall musculoskeletal network organization of the upper limb is strikingly different from that of the lower limb, particularly that of the more proximal structures of each limb. Importantly, the obtained data provide further evidence to be added to the vast amount of paleontological, gross anatomical, developmental, molecular and embryological data recently obtained that contradicts the long-standing dogma that the upper and lower limbs are serial

  1. Anatomical Network Comparison of Human Upper and Lower, Newborn and Adult, and Normal and Abnormal Limbs, with Notes on Development, Pathology and Limb Serial Homology vs. Homoplasy.

    PubMed

    Diogo, Rui; Esteve-Altava, Borja; Smith, Christopher; Boughner, Julia C; Rasskin-Gutman, Diego

    2015-01-01

    How do the various anatomical parts (modules) of the animal body evolve into very different integrated forms (integration) yet still function properly without decreasing the individual's survival? This long-standing question remains unanswered for multiple reasons, including lack of consensus about conceptual definitions and approaches, as well as a reasonable bias toward the study of hard tissues over soft tissues. A major difficulty concerns the non-trivial technical hurdles of addressing this problem, specifically the lack of quantitative tools to quantify and compare variation across multiple disparate anatomical parts and tissue types. In this paper we apply for the first time a powerful new quantitative tool, Anatomical Network Analysis (AnNA), to examine and compare in detail the musculoskeletal modularity and integration of normal and abnormal human upper and lower limbs. In contrast to other morphological methods, the strength of AnNA is that it allows efficient and direct empirical comparisons among body parts with even vastly different architectures (e.g. upper and lower limbs) and diverse or complex tissue composition (e.g. bones, cartilages and muscles), by quantifying the spatial organization of these parts-their topological patterns relative to each other-using tools borrowed from network theory. Our results reveal similarities between the skeletal networks of the normal newborn/adult upper limb vs. lower limb, with exception to the shoulder vs. pelvis. However, when muscles are included, the overall musculoskeletal network organization of the upper limb is strikingly different from that of the lower limb, particularly that of the more proximal structures of each limb. Importantly, the obtained data provide further evidence to be added to the vast amount of paleontological, gross anatomical, developmental, molecular and embryological data recently obtained that contradicts the long-standing dogma that the upper and lower limbs are serial homologues

  2. Disrupted ERK signaling during cortical development leads to abnormal progenitor proliferation, neuronal and network excitability and behavior, modeling human neuro-cardio-facial-cutaneous and related syndromes.

    PubMed

    Pucilowska, Joanna; Puzerey, Pavel A; Karlo, J Colleen; Galán, Roberto F; Landreth, Gary E

    2012-06-20

    Genetic disorders arising from copy number variations in the ERK (extracellular signal-regulated kinase) MAP (mitogen-activated protein) kinases or mutations in their upstream regulators that result in neuro-cardio-facial-cutaneous syndromes are associated with developmental abnormalities, cognitive deficits, and autism. We developed murine models of these disorders by deleting the ERKs at the beginning of neurogenesis and report disrupted cortical progenitor generation and proliferation, which leads to altered cytoarchitecture of the postnatal brain in a gene-dose-dependent manner. We show that these changes are due to ERK-dependent dysregulation of cyclin D1 and p27(Kip1), resulting in cell cycle elongation, favoring neurogenic over self-renewing divisions. The precocious neurogenesis causes premature progenitor pool depletion, altering the number and distribution of pyramidal neurons. Importantly, loss of ERK2 alters the intrinsic excitability of cortical neurons and contributes to perturbations in global network activity. These changes are associated with elevated anxiety and impaired working and hippocampal-dependent memory in these mice. This study provides a novel mechanistic insight into the basis of cortical malformation which may provide a potential link to cognitive deficits in individuals with altered ERK activity.

  3. Short-Term Environmental Enrichment Enhances Adult Neurogenesis, Vascular Network and Dendritic Complexity in the Hippocampus of Type 1 Diabetic Mice

    PubMed Central

    Beauquis, Juan; Roig, Paulina; De Nicola, Alejandro F.; Saravia, Flavia

    2010-01-01

    Background Several brain disturbances have been described in association to type 1 diabetes in humans. In animal models, hippocampal pathological changes were reported together with cognitive deficits. The exposure to a variety of environmental stimuli during a certain period of time is able to prevent brain alterations and to improve learning and memory in conditions like stress, aging and neurodegenerative processes. Methodology/Principal Findings We explored the modulation of hippocampal alterations in streptozotocin-induced type 1 diabetic mice by environmental enrichment. In diabetic mice housed in standard conditions we found a reduction of adult neurogenesis in the dentate gyrus, decreased dendritic complexity in CA1 neurons and a smaller vascular fractional area in the dentate gyrus, compared with control animals in the same housing condition. A short exposure -10 days- to an enriched environment was able to enhance proliferation, survival and dendritic arborization of newborn neurons, to recover dendritic tree length and spine density of pyramidal CA1 neurons and to increase the vascular network of the dentate gyrus in diabetic animals. Conclusions/Significance The environmental complexity seems to constitute a strong stimulator competent to rescue the diabetic brain from neurodegenerative progression. PMID:21085588

  4. Evidence for novel age-dependent network structures as a putative primo vascular network in the dura mater of the rat brain.

    PubMed

    Lee, Ho-Sung; Kang, Dai-In; Yoon, Seung Zhoo; Ryu, Yeon Hee; Lee, Inhyung; Kim, Hoon-Gi; Lee, Byung-Cheon; Lee, Ki Bog

    2015-07-01

    With chromium-hematoxylin staining, we found evidence for the existence of novel age-dependent network structures in the dura mater of rat brains. Under stereomicroscopy, we noticed that chromium-hematoxylin-stained threadlike structures, which were barely observable in 1-week-old rats, were networked in specific areas of the brain, for example, the lateral lobes and the cerebella, in 4-week-old rats. In 7-week-old rats, those structures were found to have become larger and better networked. With phase contrast microscopy, we found that in 1-week-old rats, chromium-hematoxylin-stained granules were scattered in the same areas of the brain in which the network structures would later be observed in the 4- and 7-week-old rats. Such age-dependent network structures were examined by using optical and transmission electron microscopy, and the following results were obtained. The scattered granules fused into networks with increasing age. Cross-sections of the age-dependent network structures demonstrated heavily-stained basophilic substructures. Transmission electron microscopy revealed the basophilic substructures to be clusters with high electron densities consisting of nanosized particles. We report these data as evidence for the existence of age-dependent network structures in the dura mater, we discuss their putative functions of age-dependent network structures beyond the general concept of the dura mater as a supporting matrix.

  5. Evidence for novel age-dependent network structures as a putative primo vascular network in the dura mater of the rat brain

    PubMed Central

    Lee, Ho-Sung; Kang, Dai-In; Yoon, Seung Zhoo; Ryu, Yeon Hee; Lee, Inhyung; Kim, Hoon-Gi; Lee, Byung-Cheon; Lee, Ki Bog

    2015-01-01

    With chromium-hematoxylin staining, we found evidence for the existence of novel age-dependent network structures in the dura mater of rat brains. Under stereomicroscopy, we noticed that chromium-hematoxylin-stained threadlike structures, which were barely observable in 1-week-old rats, were networked in specific areas of the brain, for example, the lateral lobes and the cerebella, in 4-week-old rats. In 7-week-old rats, those structures were found to have become larger and better networked. With phase contrast microscopy, we found that in 1-week-old rats, chromium-hematoxylin-stained granules were scattered in the same areas of the brain in which the network structures would later be observed in the 4- and 7-week-old rats. Such age-dependent network structures were examined by using optical and transmission electron microscopy, and the following results were obtained. The scattered granules fused into networks with increasing age. Cross-sections of the age-dependent network structures demonstrated heavily-stained basophilic substructures. Transmission electron microscopy revealed the basophilic substructures to be clusters with high electron densities consisting of nanosized particles. We report these data as evidence for the existence of age-dependent network structures in the dura mater, we discuss their putative functions of age-dependent network structures beyond the general concept of the dura mater as a supporting matrix. PMID:26330833

  6. Vascular pattern formation in plants.

    PubMed

    Scarpella, Enrico; Helariutta, Ykä

    2010-01-01

    Reticulate tissue systems exist in most multicellular organisms, and the principles underlying the formation of cellular networks have fascinated philosophers, mathematicians, and biologists for centuries. In particular, the beautiful and varied arrangements of vascular tissues in plants have intrigued mankind since antiquity, yet the organizing signals have remained elusive. Plant vascular tissues form systems of interconnected cell files throughout the plant body. Vascular cells are aligned with one another along continuous lines, and vascular tissues differentiate at reproducible positions within organ environments. However, neither the precise path of vascular differentiation nor the exact geometry of vascular networks is fixed or immutable. Several recent advances converge to reconcile the seemingly conflicting predictability and plasticity of vascular tissue patterns. A control mechanism in which an apical-basal flow of signal establishes a basic coordinate system for body axis formation and vascular strand differentiation, and in which a superimposed level of radial organizing cues elaborates cell patterns, would generate a reproducible tissue configuration in the context of an underlying robust, self-organizing structure, and account for the simultaneous regularity and flexibility of vascular tissue patterns.

  7. Exogenous vascular endothelial growth factor induces malformed and hyperfused vessels during embryonic neovascularization.

    PubMed Central

    Drake, C J; Little, C D

    1995-01-01

    Vascular endothelial growth factor (VEGF) is a potent and specific endothelial mitogen that is able to induce angiogenesis in vivo [Leung, D. W., Cachianes, G., Kuang, W.-J., Goeddel, D. V. & Ferrara, N. (1989) Science 246 1306-1309]. To determine if VEGF also influences the behavior of primordial endothelial cells, we used an in vivo vascular assay based on the de novo formation of vessels. Japanese quail embryos injected with nanomolar quantities of the 165-residue form of VEGF at the onset of vasculogenesis exhibited profoundly altered vessel development. In fact, the overall patterning of the vascular network was abnormal in all VEGF-injected embryos. The malformations were attributable to two specific endothelial cell activities: (i) inappropriate neovascularization in normally avascular areas and (ii) the unregulated, excessive fusion of vessels. In the first instance, supernumerary vessels directly linked the inflow channel of the heart to the aortic outflow channel. The second aberrant activity led to the formation of vessels with abnormally large lumens. Ultimately, unregulated vessel fusion generated massive vascular sacs that obliterated the identity of individual vessels. These observations show that exogenous VEGF has an impact on the behavior of primordial endothelial cells engaged in vasculogenesis, and they strongly suggest that endogenous VEGF is important in vascular patterning and regulation of vessel size (lumen formation). Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:7543999

  8. Fibulin-4 E57K Knock-in Mice Recapitulate Cutaneous, Vascular and Skeletal Defects of Recessive Cutis Laxa 1B with both Elastic Fiber and Collagen Fibril Abnormalities.

    PubMed

    Igoucheva, Olga; Alexeev, Vitali; Halabi, Carmen M; Adams, Sheila M; Stoilov, Ivan; Sasaki, Takako; Arita, Machiko; Donahue, Adele; Mecham, Robert P; Birk, David E; Chu, Mon-Li

    2015-08-28

    Fibulin-4 is an extracellular matrix protein essential for elastic fiber formation. Frameshift and missense mutations in the fibulin-4 gene (EFEMP2/FBLN4) cause autosomal recessive cutis laxa (ARCL) 1B, characterized by loose skin, aortic aneurysm, arterial tortuosity, lung emphysema, and skeletal abnormalities. Homozygous missense mutations in FBLN4 are a prevalent cause of ARCL 1B. Here we generated a knock-in mouse strain bearing a recurrent fibulin-4 E57K homozygous missense mutation. The mutant mice survived into adulthood and displayed abnormalities in multiple organ systems, including loose skin, bent forelimb, aortic aneurysm, tortuous artery, and pulmonary emphysema. Biochemical studies of dermal fibroblasts showed that fibulin-4 E57K mutant protein was produced but was prone to dimer formation and inefficiently secreted, thereby triggering an endoplasmic reticulum stress response. Immunohistochemistry detected a low level of fibulin-4 E57K protein in the knock-in skin along with altered expression of selected elastic fiber components. Processing of a precursor to mature lysyl oxidase, an enzyme involved in cross-linking of elastin and collagen, was compromised. The knock-in skin had a reduced level of desmosine, an elastin-specific cross-link compound, and ultrastructurally abnormal elastic fibers. Surprisingly, structurally aberrant collagen fibrils and altered organization into fibers were characteristics of the knock-in dermis and forelimb tendons. Type I collagen extracted from the knock-in skin had decreased amounts of covalent intermolecular cross-links, which could contribute to the collagen fibril abnormalities. Our studies provide the first evidence that fibulin-4 plays a role in regulating collagen fibril assembly and offer a preclinical platform for developing treatments for ARCL 1B.

  9. Measuring Vascular Permeability In Vivo.

    PubMed

    Meijer, Eelco F J; Baish, James W; Padera, Timothy P; Fukumura, Dai

    2016-01-01

    Over the past decades, in vivo vascular permeability measurements have provided significant insight into vascular functions in physiological and pathophysiological conditions such as the response to pro- and anti-angiogenic signaling, abnormality of tumor vasculature and its normalization, and delivery and efficacy of therapeutic agents. Different approaches for vascular permeability measurements have been established. Here, we describe and discuss a conventional 2D imaging method to measure vascular permeability, which was originally documented by Gerlowski and Jain in 1986 (Microvasc Res 31:288-305, 1986) and further developed by Yuan et al. in the early 1990s (Microvasc Res 45:269-289, 1993; Cancer Res 54:352-3356, 1994), and our recently developed 3D imaging method, which advances the approach originally described by Brown et al. in 2001 (Nat Med 7:864-868, 2001). PMID:27581015

  10. Vascular Diseases

    MedlinePlus

    ... heart and blood vessels, such as diabetes or high cholesterol Smoking Obesity Losing weight, eating healthy foods, being active and not smoking can help vascular disease. Other treatments include medicines and surgery.

  11. Overgrowth syndromes with vascular anomalies.

    PubMed

    Blei, Francine

    2015-04-01

    Overgrowth syndromes with vascular anomalies encompass entities with a vascular anomaly as the predominant feature vs those syndromes with predominant somatic overgrowth and a vascular anomaly as a more minor component. The focus of this article is to categorize these syndromes phenotypically, including updated clinical criteria, radiologic features, evaluation, management issues, pathophysiology, and genetic information. A literature review was conducted in PubMed using key words "overgrowth syndromes and vascular anomalies" as well as specific literature reviews for each entity and supportive genetic information (e.g., somatic mosaicism). Additional searches in OMIM and Gene Reviews were conducted for each syndrome. Disease entities were categorized by predominant clinical features, known genetic information, and putative affected signaling pathway. Overgrowth syndromes with vascular anomalies are a heterogeneous group of disorders, often with variable clinical expression, due to germline or somatic mutations. Overgrowth can be focal (e.g., macrocephaly) or generalized, often asymmetrically (and/or mosaically) distributed. All germ layers may be affected, and the abnormalities may be progressive. Patients with overgrowth syndromes may be at an increased risk for malignancies. Practitioners should be attentive to patients having syndromes with overgrowth and vascular defects. These patients require proactive evaluation, referral to appropriate specialists, and in some cases, early monitoring for potential malignancies. Progress in identifying vascular anomaly-related overgrowth syndromes and their genetic etiology has been robust in the past decade and is contributing to genetically based prenatal diagnosis and new therapies targeting the putative causative genetic mutations. PMID:25937473

  12. Overgrowth syndromes with vascular anomalies.

    PubMed

    Blei, Francine

    2015-04-01

    Overgrowth syndromes with vascular anomalies encompass entities with a vascular anomaly as the predominant feature vs those syndromes with predominant somatic overgrowth and a vascular anomaly as a more minor component. The focus of this article is to categorize these syndromes phenotypically, including updated clinical criteria, radiologic features, evaluation, management issues, pathophysiology, and genetic information. A literature review was conducted in PubMed using key words "overgrowth syndromes and vascular anomalies" as well as specific literature reviews for each entity and supportive genetic information (e.g., somatic mosaicism). Additional searches in OMIM and Gene Reviews were conducted for each syndrome. Disease entities were categorized by predominant clinical features, known genetic information, and putative affected signaling pathway. Overgrowth syndromes with vascular anomalies are a heterogeneous group of disorders, often with variable clinical expression, due to germline or somatic mutations. Overgrowth can be focal (e.g., macrocephaly) or generalized, often asymmetrically (and/or mosaically) distributed. All germ layers may be affected, and the abnormalities may be progressive. Patients with overgrowth syndromes may be at an increased risk for malignancies. Practitioners should be attentive to patients having syndromes with overgrowth and vascular defects. These patients require proactive evaluation, referral to appropriate specialists, and in some cases, early monitoring for potential malignancies. Progress in identifying vascular anomaly-related overgrowth syndromes and their genetic etiology has been robust in the past decade and is contributing to genetically based prenatal diagnosis and new therapies targeting the putative causative genetic mutations.

  13. [Emotion Disorders and Abnormal Perspiration].

    PubMed

    Umeda, Satoshi

    2016-08-01

    This article reviewed the relationship between emotional disorders and abnormal perspiration. First, I focused on local brain areas related to emotional processing, and summarized the functions of the emotional network involving those local areas. Functional disorders followed by the damage in the amygdala, orbitofrontal cortex, and insular cortex were reviewed, including related abnormal perspiration. I then addressed the mechanisms of how autonomic disorders influence emotional processing. Finally, possible future directions for integrated understanding of the connection between neural activities and bodily reactions were discussed. PMID:27503817

  14. [Emotion Disorders and Abnormal Perspiration].

    PubMed

    Umeda, Satoshi

    2016-08-01

    This article reviewed the relationship between emotional disorders and abnormal perspiration. First, I focused on local brain areas related to emotional processing, and summarized the functions of the emotional network involving those local areas. Functional disorders followed by the damage in the amygdala, orbitofrontal cortex, and insular cortex were reviewed, including related abnormal perspiration. I then addressed the mechanisms of how autonomic disorders influence emotional processing. Finally, possible future directions for integrated understanding of the connection between neural activities and bodily reactions were discussed.

  15. Social media in vascular surgery.

    PubMed

    Indes, Jeffrey E; Gates, Lindsay; Mitchell, Erica L; Muhs, Bart E

    2013-04-01

    There has been a tremendous growth in the use of social media to expand the visibility of various specialties in medicine. The purpose of this paper is to describe the latest updates on some current applications of social media in the practice of vascular surgery as well as existing limitations of use. This investigation demonstrates that the use of social networking sites appears to have a positive impact on vascular practice, as is evident through the incorporation of this technology at the Cleveland Clinic and by the Society for Vascular Surgery into their approach to patient care and physician communication. Overall, integration of social networking technology has current and future potential to be used to promote goals, patient awareness, recruitment for clinical trials, and professionalism within the specialty of vascular surgery. PMID:23321344

  16. [Vascular dementia].

    PubMed

    Peters, N; Dichgans, M

    2010-10-01

    Vascular dementia (VaD) constitutes the second most frequent cause of dementia following Alzheimer's disease (AD). In contrast to AD, VaD encompasses a variety of conditions and dementia mechanisms including multiple and strategic infarcts, widespread white matter lesions and hemorrhages. The diagnosis of VaD is based on the patient history, the clinical evaluation and neuroimaging. Treatment of VaD should account for the underlying vascular condition and is directed towards the control of vascular risk factors and stroke prevention. The need for early diagnosis and preventive treatment has promoted the concept of vascular cognitive impairment (VCI). Harmonization standards for the description and study of VCI have recently been published. A common and distinct subtype of VaD is subcortical ischemic vascular dementia (SIVD) which is related to cerebral small vessel disease. SIVD is clinically characterized by impairment of executive functions and processing speed with relatively preserved memory. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a genetic variant of SIVD, represents an important differential diagnosis and may serve as a model of SIVD.

  17. Characterization of vascular tree architecture using the Tokunaga taxonomy

    NASA Astrophysics Data System (ADS)

    Galarreta-Valverde, Miguel A.; Zoghbi, Jihan M.; Pereira, Fabricio; Beregi, Jean-Paul; Mekkaoui, Choukri; Jackowski, Marcel P.

    2015-03-01

    The diagnosis of cardiovascular disease is usually assisted by resonance angiography (MRA) or computed tomography angiography (CTA) imaging. The identification of abnormal vascular architecture from angiographic three-dimensional images is therefore crucial to the diagnosis of cardiovascular disease. Automated detection and quantification of vascular structure and architecture thus holds significant clinical value. In this work, we employ a Lindenmayer system to represent vascular trees from angiographic images and describe a quantitative measure based on the Tokunaga taxonomy to differentiate vascular architectures. Synthetic vessel architectures with varying bifurcation patterns were compared and results showed that this architectural measure is proportional to the level of branching. In real MRA images, this measure was able to differentiate between normal and abnormal intracerebral vasculature containing an aneurysm. Hence, this methodology not only allows for compact representation of vascular architectures but also provides a quantitative metric of bifurcation complexity, which has the potential to characterize different types of vascular abnormalities.

  18. VESGEN Software for Mapping and Quantification of Vascular Regulators

    NASA Technical Reports Server (NTRS)

    Parsons-Wingerter, Patricia A.; Vickerman, Mary B.; Keith, Patricia A.

    2012-01-01

    VESsel GENeration (VESGEN) Analysis is an automated software that maps and quantifies effects of vascular regulators on vascular morphology by analyzing important vessel parameters. Quantification parameters include vessel diameter, length, branch points, density, and fractal dimension. For vascular trees, measurements are reported as dependent functions of vessel branching generation. VESGEN maps and quantifies vascular morphological events according to fractal-based vascular branching generation. It also relies on careful imaging of branching and networked vascular form. It was developed as a plug-in for ImageJ (National Institutes of Health, USA). VESGEN uses image-processing concepts of 8-neighbor pixel connectivity, skeleton, and distance map to analyze 2D, black-and-white (binary) images of vascular trees, networks, and tree-network composites. VESGEN maps typically 5 to 12 (or more) generations of vascular branching, starting from a single parent vessel. These generations are tracked and measured for critical vascular parameters that include vessel diameter, length, density and number, and tortuosity per branching generation. The effects of vascular therapeutics and regulators on vascular morphology and branching tested in human clinical or laboratory animal experimental studies are quantified by comparing vascular parameters with control groups. VESGEN provides a user interface to both guide and allow control over the users vascular analysis process. An option is provided to select a morphological tissue type of vascular trees, network or tree-network composites, which determines the general collections of algorithms, intermediate images, and output images and measurements that will be produced.

  19. Vascular emergencies.

    PubMed

    Semashko, D C

    1997-01-01

    This article reviews the initial assessment and emergent management of several common as well as uncommon vascular emergencies. Aortic dissection, aneurysms, and arterial occlusive disease are familiar but challenging clinical entities. Less frequently encountered conditions are also discussed including an aortic enteric fistula, mesenteric venous thrombosis, phlegmasia alba dolens, and subclavian vein thrombosis.

  20. Hemorheological abnormalities in human arterial hypertension

    NASA Astrophysics Data System (ADS)

    Lo Presti, Rosalia; Hopps, Eugenia; Caimi, Gregorio

    2014-05-01

    Blood rheology is impaired in hypertensive patients. The alteration involves blood and plasma viscosity, and the erythrocyte behaviour is often abnormal. The hemorheological pattern appears to be related to some pathophysiological mechanisms of hypertension and to organ damage, in particular left ventricular hypertrophy and myocardial ischemia. Abnormalities have been observed in erythrocyte membrane fluidity, explored by fluorescence spectroscopy and electron spin resonance. This may be relevant for red cell flow in microvessels and oxygen delivery to tissues. Although blood viscosity is not a direct target of antihypertensive therapy, the rheological properties of blood play a role in the pathophysiology of arterial hypertension and its vascular complications.

  1. Blood Vessel Maturation in Health and Disease and its Implications for Vascularization of Engineered Tissues.

    PubMed

    Sun, Xuetao; Evren, Sevan; Nunes, Sara S

    2015-01-01

    Engineered blood vessels have often been found to be immature and unstable. Similarly, numerous pathologies such as diabetic retinopathy and cancer are characterized by highly abnormal, defective, hypervascular networks, consisting of immature, leaky, and irregular vessels with a marked loss of perivascular cell coverage. An emerging therapeutic concept in treatment of such vascular diseases and their management is the potential to normalize blood vessels by strengthening the cellular components that form the vascular network. Vessel normalization is characterized by the reduction in the number and size of immature vessels, a decrease in interstitial fluid pressure, and increase in perivascular cell coverage. Understanding the molecular and cellular defects associated with abnormal blood vessels will allow us to find appropriate treatment options that can promote normal blood vessel development. These, in turn, can be applied to improve vessel maturation in engineered tissues. In this review, we describe the major perivascular abnormalities associated with various human diseases and engineered vasculatures and the major advances in obtaining mature vasculatures for translational applications.

  2. The Society for Vascular Surgery Vascular Quality Initiative.

    PubMed

    Cronenwett, Jack L; Kraiss, Larry W; Cambria, Richard P

    2012-05-01

    The Society for Vascular Surgery (SVS) Vascular Quality Initiative (VQI) is designed to improve the quality, safety, effectiveness, and cost of vascular health care. It uses the structure of a Patient Safety Organization to permit collection of patient-identified information but protect benchmarked comparisons from legal discovery. The SVS VQI is uniquely organized as a distributed network of regional quality groups to facilitate local translation of registry data into practice change while maintaining the power of a national registry. Detailed data specific to each commonly performed open and endovascular procedure are collected, both in-hospital and at ≥ 1 year of follow-up. Quality measures are reported to physicians and hospitals, which allow anonymous risk-adjusted benchmarking within regions or nationally. All specialties that perform vascular procedures are included, and international participation is encouraged. This review describes the current status of the SVS VQI.

  3. Neurobiology of Vascular Dementia

    PubMed Central

    Enciu, Ana-Maria; Constantinescu, Stefan N.; Popescu, Laurenţiu M.; Mureşanu, Dafin F.; Popescu, Bogdan O.

    2011-01-01

    Vascular dementia is, in its current conceptual form, a distinct type of dementia with a spectrum of specific clinical and pathophysiological features. However, in a very large majority of cases, these alterations occur in an already aged brain, characterized by a milieu of cellular and molecular events common for different neurodegenerative diseases. The cell signaling defects and molecular dyshomeostasis might lead to neuronal malfunction prior to the death of neurons and the alteration of neuronal networks. In the present paper, we explore some of the molecular mechanisms underlying brain malfunction triggered by cerebrovascular disease and risk factors. We suggest that, in the age of genetic investigation and molecular diagnosis, the concept of vascular dementia needs a new approach. PMID:21876809

  4. Network of vascular diseases, death and biochemical characteristics in a set of 4,197 patients with type 1 diabetes (The FinnDiane Study)

    PubMed Central

    Mäkinen, Ville-Petteri; Forsblom, Carol; Thorn, Lena M; Wadén, Johan; Kaski, Kimmo; Ala-Korpela, Mika; Groop, Per-Henrik

    2009-01-01

    Background Cardiovascular disease is the main cause of premature death in patients with type 1 diabetes. Patients with diabetic kidney disease have an increased risk of heart attack or stroke. Accurate knowledge of the complex inter-dependencies between the risk factors is critical for pinpointing the best targets for research and treatment. Therefore, the aim of this study was to describe the association patterns between clinical and biochemical features of diabetic complications. Methods Medical records and serum and urine samples of 4,197 patients with type 1 diabetes were collected from health care centers in Finland. At baseline, the mean diabetes duration was 22 years, 52% were male, 23% had kidney disease (urine albumin excretion over 300 mg/24 h or end-stage renal disease) and 8% had a history of macrovascular events. All-cause mortality was evaluated after an average of 6.5 years of follow-up (25,714 patient years). The dataset comprised 28 clinical and 25 biochemical variables that were regarded as the nodes of a network to assess their mutual relationships. Results The networks contained cliques that were densely inter-connected (r > 0.6), including cliques for high-density lipoprotein (HDL) markers, for triglycerides and cholesterol, for urinary excretion and for indices of body mass. The links between the cliques showed biologically relevant interactions: an inverse relationship between HDL cholesterol and the triglyceride clique (r < -0.3, P < 10-16), a connection between triglycerides and body mass via C-reactive protein (r > 0.3, P < 10-16) and intermediate-density cholesterol as the connector between lipoprotein metabolism and albuminuria (r > 0.3, P < 10-16). Aging and macrovascular disease were linked to death via working ability and retinopathy. Diabetic kidney disease, serum creatinine and potassium, retinopathy and blood pressure were inter-connected. Blood pressure correlations indicated accelerated vascular aging in individuals with kidney

  5. Heath monitoring of a glass transfer robot in the mass production line of liquid crystal display using abnormal operating sounds based on wavelet packet transform and artificial neural network

    NASA Astrophysics Data System (ADS)

    Kim, Eui-Youl; Lee, Young-Joon; Lee, Sang-Kwon

    2012-07-01

    This paper presents the fault detect method of a moving transfer robot in the mass production line of liquid crystal display (LCD) manufacturers based on the wavelet packet transform (WPT) for feature extraction and the artificial neural network (ANN) for fault classification. Most of fault detection methods in a mechanical system have been researched based on the vibration signal. Unlike the existing methodologies, this study aims to minimize the uncertainty of a field engineer's decision making process for determining whether a fault is present or not based on the human auditory perception by developing a fault diagnosis system that uses the abnormal operating sound radiated from a moving transfer robot as a source signal. Abnormal operating sound radiated from a moving transfer robot has been used for this work instead of other source signals such as vibration, acoustic emission, electrical signal, etc. Its advantage as a source signal makes it possible to monitor the status of multiple faults by using only a microphone despite a relatively low sensitivity. In the application of ANN, since it is important to minimize the error of trained ANN in terms of the accuracy of fault diagnosis logic, in the paper, the number of input and target data samples was increased through a regeneration process based on statistical properties, and then the uncorrelated nodes in the input vector were also removed to improve the orthogonality of the input vector based on the entropy based feature selection method. Consequently, it can be concluded that the abnormal operating sound is sufficiently useful as a source signal for the fault diagnosis of mechanical components as well as other source signals.

  6. Tooth - abnormal shape

    MedlinePlus

    Hutchinson incisors; Abnormal tooth shape; Peg teeth; Mulberry teeth; Conical teeth ... The appearance of normal teeth varies, especially the molars. ... conditions. Specific diseases can affect tooth shape, tooth ...

  7. A multidisciplinary network for the care of abnormal fatigue and chronic fatigue syndrome in the provinces of East and West Flanders in Belgium.

    PubMed

    Tobback, E; Mariman, A; Heytens, S; Declercq, T; Bouwen, A; Spooren, D; Snoeck, P; Van Dessel, K; D'Hooghe, S; Rimbaut, S; Vogelaers, D

    2014-10-01

    The organization of care for patients with the chronic fatigue syndrome (CFS) in tertiary care referral centres from 2002 onwards, was negatively evaluated by the Belgian Health Care Knowledge Centre on the endpoint of socio-professional reintegration. Subsequently, the federal health authorities asked for the elaboration of a new and innovative model of stepped care, aiming at improved integration of diagnosis and treatment into primary care and between levels of health care for patients with CFS. The reference centre of the University Hospital Ghent took the initiative of recruiting partners in the Belgian provinces of East and West Flanders to guarantee the care for patients with medically unexplained symptoms, in particular abnormal fatigue and CFS. A new and innovative care model, in which general practitioners play a central role, emphasizes the importance of early recognition of the patient 'at risk', correct diagnosis and timely referral. Early detection and intervention is essential in order to avoid or minimize illness progression towards chronicity, to safeguard opportunities for significant health improvement as well as to enhance successful socio-professional reintegration. This approach covers both the large sample of patients developing somatic complaints without obvious disease in an early phase as well as the more limited group of patients with chronic illness, including CFS. Cognitive behavioural therapy and graded exposure/exercise therapy are the evidence based main components of therapy in the latter. A biopsychosocial model underlies the proposed path of care.

  8. Structurally abnormal human autosomes

    SciTech Connect

    1993-12-31

    Chapter 25, discusses structurally abnormal human autosomes. This discussion includes: structurally abnormal chromosomes, chromosomal polymorphisms, pericentric inversions, paracentric inversions, deletions or partial monosomies, cri du chat (cat cry) syndrome, ring chromosomes, insertions, duplication or pure partial trisomy and mosaicism. 71 refs., 8 figs.

  9. Vascular Normalization as a Therapeutic Strategy for Malignant and Nonmalignant Disease

    PubMed Central

    Goel, Shom; Wong, Andus Hon-Kit; Jain, Rakesh K.

    2012-01-01

    Pathological angiogenesis—driven by an imbalance of pro- and antiangiogenic signaling—is a hallmark of many diseases, both malignant and benign. Unlike in the healthy adult in which angiogenesis is tightly regulated, such diseases are characterized by uncontrolled new vessel formation, resulting in a microvascular network characterized by vessel immaturity, with profound structural and functional abnormalities. The consequence of these abnormalities is further modification of the microenvironment, often serving to fuel disease progression and attenuate response to conventional therapies. In this article, we present the “vascular normalization” hypothesis, which states that antiangiogenic therapy, by restoring the balance between pro- and antiangiogenic signaling, can induce a more structurally and functionally normal vasculature in a variety of diseases. We present the preclinical and clinical evidence supporting this concept and discuss how it has contributed to successful treatment of both solid tumors and several benign conditions. PMID:22393532

  10. Morphological abnormalities among lampreys

    USGS Publications Warehouse

    Manion, Patrick J.

    1967-01-01

    The experimental control of the sea lamprey (Petromyzon marinus) in the Great Lakes has required the collection of thousands of lampreys. Representatives of each life stage of the four species of the Lake Superior basin were examined for structural abnormalities. The most common aberration was the presence of additional tails. The accessory tails were always postanal and smaller than the normal tail. The point of origin varied; the extra tails occurred on dorsal, ventral, or lateral surfaces. Some of the extra tails were misshaped and curled, but others were normal in shape and pigment pattern. Other abnormalities in larval sea lampreys were malformed or twisted tails and bodies. The cause of the structural abnormalities is unknown. The presence of extra caudal fins could be genetically controlled, or be due to partial amputation or injury followed by abnormal regeneration. Few if any lampreys with structural abnormalities live to sexual maturity.

  11. NASAs VESGEN: Systems Analysis of Vascular Phenotypes from Stress and Other Signaling Pathways Using GeneLab.

    NASA Technical Reports Server (NTRS)

    Parsons-Wingerter, Patricia A.; Weitzel, Alexander; Vyas, Ruchi J.; Murray, Matthew C.; Wyatt, Sarah E.

    2016-01-01

    One fundamental requirement shared by humans with all higher terrestrial life forms, including insect wings, higher land plants and other vertebrates, is a complex, fractally branching vascular system. NASA's VESsel GENeration Analysis (VESGEN) software maps and quantifies vascular trees, networks, and tree-network composites according to weighted physiological rules such as vessel connectivity, tapering and bifurcational branching. According to fluid dynamics, successful vascular transport requires a complex distributed system of highly regulated laminar flow. Microvascular branching rules within vertebrates, dicot leaves and the other organisms therefore display many similarities. One unifying perspective is that vascular patterning offers a useful readout that necessarily integrates complex molecular signaling pathways. VESGEN has elucidated changes in vascular pattern resulting from inflammatory, stress response, developmental and other signaling within numerous tissues and major model organisms studied for Space Biology. For a new VESGEN systems approach, we analyzed differential gene expression in leaves of Arabidopsis thaliana reported by GeneLab (GLDS-7) for spaceflight. Vascular-related changes in leaf gene expression were identified that can potentially be phenocopied by mutants in ground-based experiments. To link transcriptional, protein and other molecular change with phenotype, alterations in the Euclidean and dynamic dimensions (x,y,t) of vascular patterns for Arabidopsis leaves and other model species are being co-localized with signaling patterns of single molecular expression analyzed as information dimensions (i,j,k,...). Previously, Drosophila microarray data returned from space suggested significant changes in genes related to wing venation development that include EGF, Notch, Hedghog, Wingless and Dpp signaling. Phenotypes of increasingly abnormal ectopic wing venation in the (non-spaceflight) Drosophila wing generated by overexpression of a

  12. Cell-based strategies for vascular regeneration.

    PubMed

    Zou, Tongqiang; Fan, Jiabing; Fartash, Armita; Liu, Haifeng; Fan, Yubo

    2016-05-01

    Vascular regeneration is known to play an essential role in the repair of injured tissues mainly through accelerating the repair of vascular injury caused by vascular diseases, as well as the recovery of ischemic tissues. However, the clinical vascular regeneration is still challenging. Cell-based therapy is thought to be a promising strategy for vascular regeneration, since various cells have been identified to exert important influences on the process of vascular regeneration such as the enhanced endothelium formation on the surface of vascular grafts, and the induction of vessel-like network formation in the ischemic tissues. Here are a vast number of diverse cell-based strategies that have been extensively studied in vascular regeneration. These strategies can be further classified into three main categories, including cell transplantation, construction of tissue-engineered grafts, and surface modification of scaffolds. Cells used in these strategies mainly refer to terminally differentiated vascular cells, pluripotent stem cells, multipotent stem cells, and unipotent stem cells. The aim of this review is to summarize the reported research advances on the application of various cells for vascular regeneration, yielding insights into future clinical treatment for injured tissue/organ. PMID:26864677

  13. Hemodynamic assessment and acute pulmonary vasoreactivity testing in the evaluation of children with pulmonary vascular disease. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK.

    PubMed

    Apitz, Christian; Hansmann, Georg; Schranz, Dietmar

    2016-05-01

    Invasive assessment of haemodynamics (ventricular, pulmonary) and testing of acute vasoreactivity in the catheterisation laboratory remain the gold standard for the diagnosis of pulmonary hypertension (PH) and pulmonary hypertensive vascular disease. However, these measurements and the interpretation thereof are challenging due to the heterogeneous aetiology of PH in childhood and potentially confounding factors in the catheterisation laboratory. Patients with pulmonary arterial hypertension (PAH) associated with congenital heart disease who have a cardiovascular shunt need to undergo a completely different catheterisation approach than those with idiopathic PAH lacking an anatomical cardiovascular defect. Diagnostic cardiac catheterisation of children with suspected PH usually includes right and left heart catheterisation, particularly for the initial assessment (ie, at the time of diagnosis), and should be performed in experienced centres only. Here, we present graded consensus recommendations for the invasive evaluation of children with PH including those with pulmonary hypertensive vascular disease and/or ventricular dysfunction. Based on the limited published studies and our own experience we suggest a structured catheterisation protocol and two separate definitions of positive acute vasoreactivity testing (AVT): (1) AVT to assess prognosis and indication for specific PH therapy, and (2) AVT to assess operability of PAH associated with congenital heart disease. The protocol and the latter definitions may help in the systematic assessment of these patients and the interpretation of the obtained data. Beyond an accurate diagnosis in the individual patient, such a structured approach may allow systematic decision making for the initiation of a specific treatment and may assist in estimating disease progression and individual prognosis.

  14. Hemodynamic assessment and acute pulmonary vasoreactivity testing in the evaluation of children with pulmonary vascular disease. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK.

    PubMed

    Apitz, Christian; Hansmann, Georg; Schranz, Dietmar

    2016-05-01

    Invasive assessment of haemodynamics (ventricular, pulmonary) and testing of acute vasoreactivity in the catheterisation laboratory remain the gold standard for the diagnosis of pulmonary hypertension (PH) and pulmonary hypertensive vascular disease. However, these measurements and the interpretation thereof are challenging due to the heterogeneous aetiology of PH in childhood and potentially confounding factors in the catheterisation laboratory. Patients with pulmonary arterial hypertension (PAH) associated with congenital heart disease who have a cardiovascular shunt need to undergo a completely different catheterisation approach than those with idiopathic PAH lacking an anatomical cardiovascular defect. Diagnostic cardiac catheterisation of children with suspected PH usually includes right and left heart catheterisation, particularly for the initial assessment (ie, at the time of diagnosis), and should be performed in experienced centres only. Here, we present graded consensus recommendations for the invasive evaluation of children with PH including those with pulmonary hypertensive vascular disease and/or ventricular dysfunction. Based on the limited published studies and our own experience we suggest a structured catheterisation protocol and two separate definitions of positive acute vasoreactivity testing (AVT): (1) AVT to assess prognosis and indication for specific PH therapy, and (2) AVT to assess operability of PAH associated with congenital heart disease. The protocol and the latter definitions may help in the systematic assessment of these patients and the interpretation of the obtained data. Beyond an accurate diagnosis in the individual patient, such a structured approach may allow systematic decision making for the initiation of a specific treatment and may assist in estimating disease progression and individual prognosis. PMID:27053694

  15. Abnormal uterine bleeding.

    PubMed

    Jennings, J C

    1995-11-01

    Physicians who care for female patients cannot avoid the frequent complaint of abnormal uterine bleeding. Knowledge of the disorders that cause this problem can prevent serious consequences in many patients and improve the quality of life for many others. The availability of noninvasive and minimally invasive diagnostic studies and minimally invasive surgical treatment has revolutionized management of abnormal uterine bleeding. Similar to any other disorder, the extent to which a physician manages abnormal uterine bleeding depends on his or her own level of comfort. When limitations of either diagnostic or therapeutic capability are encountered, consultation and referral should be used to the best interest of patients.

  16. Multi-voxel pattern analysis (MVPA) reveals abnormal fMRI activity in both the “core” and “extended” face network in congenital prosopagnosia

    PubMed Central

    Rivolta, Davide; Woolgar, Alexandra; Palermo, Romina; Butko, Marina; Schmalzl, Laura; Williams, Mark A.

    2014-01-01

    The ability to identify faces is mediated by a network of cortical and subcortical brain regions in humans. It is still a matter of debate which regions represent the functional substrate of congenital prosopagnosia (CP), a condition characterized by a lifelong impairment in face recognition, and affecting around 2.5% of the general population. Here, we used functional Magnetic Resonance Imaging (fMRI) to measure neural responses to faces, objects, bodies, and body-parts in a group of seven CPs and ten healthy control participants. Using multi-voxel pattern analysis (MVPA) of the fMRI data we demonstrate that neural activity within the “core” (i.e., occipital face area and fusiform face area) and “extended” (i.e., anterior temporal cortex) face regions in CPs showed reduced discriminability between faces and objects. Reduced differentiation between faces and objects in CP was also seen in the right parahippocampal cortex. In contrast, discriminability between faces and bodies/body-parts and objects and bodies/body-parts across the ventral visual system was typical in CPs. In addition to MVPA analysis, we also ran traditional mass-univariate analysis, which failed to show any group differences in face and object discriminability. In sum, these findings demonstrate (i) face-object representations impairments in CP which encompass both the “core” and “extended” face regions, and (ii) superior power of MVPA in detecting group differences. PMID:25431556

  17. "Jeopardy" in Abnormal Psychology.

    ERIC Educational Resources Information Center

    Keutzer, Carolin S.

    1993-01-01

    Describes the use of the board game, Jeopardy, in a college level abnormal psychology course. Finds increased student interaction and improved application of information. Reports generally favorable student evaluation of the technique. (CFR)

  18. Abnormal Uterine Bleeding

    MedlinePlus

    ... Abnormal uterine bleeding is any bleeding from the uterus (through your vagina) other than your normal monthly ... or fibroids (small and large growths) in the uterus can also cause bleeding. Rarely, a thyroid problem, ...

  19. Abnormal Uterine Bleeding FAQ

    MedlinePlus

    ... as cancer of the uterus, cervix, or vagina • Polycystic ovary syndrome How is abnormal bleeding diagnosed? Your health care ... before the fetus can survive outside the uterus. Polycystic Ovary Syndrome: A condition characterized by two of the following ...

  20. Abnormal Web Usage Control by Proxy Strategies.

    ERIC Educational Resources Information Center

    Yu, Hsiang-Fu; Tseng, Li-Ming

    2002-01-01

    Approaches to designing a proxy server with Web usage control and to making the proxy server effective on local area networks are proposed to prevent abnormal Web access and to prioritize Web usage. A system is implemented to demonstrate the approaches. The implementation reveals that the proposed approaches are effective, such that the abnormal…

  1. Vascular Integrity in the Pathogenesis of Brain Arteriovenous Malformation

    PubMed Central

    Zhang, Rui; Zhu, Wan

    2015-01-01

    Brain arteriovenous malformation (bAVM) is an important cause of intracranial hemorrhage (ICH), particularly in the young population. ICH is the first clinical symptom in about 50 % of bAVM patients. The vessels in bAVM are fragile and prone to rupture, causing bleeding into the brain. About 30 % of unruptured and non-hemorrhagic bAVMs demonstrate microscopic evidence of hemosiderin in the vascular wall. In bAVM mouse models, vascular mural cell coverage is reduced in the AVM lesion, accompanied by vascular leakage and microhemorrhage. In this review, we discuss possible signaling pathways involved in abnormal vascular development in bAVM. PMID:26463919

  2. Digital vascular imaging and selective renin sampling in evaluation of vascular anatomy in renal transplant recipients.

    PubMed Central

    Khoury, G A; Irving, J D; Farrington, K; Varghese, Z; Persaud, J W; Sweny, P; Moorhead, J F; Fernando, O N

    1983-01-01

    Sixty-five renal transplant recipients underwent digital vascular imaging of the graft and simultaneous selective venous sampling for plasma renin activity. Renal artery stenosis was found in seven patients but did not appear to be functionally important. Diffuse intrarenal arterial attenuation was found in seven patients and was associated with impaired graft function and perfusion; it may indicate chronic rejection. Lower pole hypoperfusion was found in nine patients without impaired graft function or perfusion; its clinical relevance is uncertain. Aneurysmal dilatation of the main renal artery was found in two patients. Severe hypertension was common in patients with these three major abnormalities, but a causal association between the abnormality and hypertension could rarely be inferred. It may be the abnormalities on digital vascular imaging, especially diffuse intrarenal arterial attenuation and lower pole hypoperfusion, are secondary to severe hypertension. Digital vascular imaging with simultaneous selective venous sampling for plasma renin activity is useful in evaluating the vascular anatomy of the grafted kidney and in assessing any abnormality found. The combined procedure was well tolerated by all patients with no complications and no incidence of acute tubular dysfunction or proteinuria after the investigation. Images p1005-a PMID:6403169

  3. An ongoing role of α-calcitonin gene-related peptide as part of a protective network against hypertension, vascular hypertrophy, and oxidative stress.

    PubMed

    Smillie, Sarah-Jane; King, Ross; Kodji, Xenia; Outzen, Emilie; Pozsgai, Gabor; Fernandes, Elizabeth; Marshall, Nichola; de Winter, Patricia; Heads, Richard J; Dessapt-Baradez, Cecile; Gnudi, Luigi; Sams, Anette; Shah, Ajay M; Siow, Richard C; Brain, Susan D

    2014-05-01

    α-Calcitonin gene-related peptide (αCGRP) is a vasodilator, but there is limited knowledge of its long-term cardiovascular protective influence. We hypothesized that αCGRP protects against the onset and development of angiotensin II-induced hypertension and have identified protective mechanisms at the vascular level. Wild-type and αCGRP knockout mice that have similar baseline blood pressure were investigated in the angiotensin II hypertension model for 14 and 28 days. αCGRP knockout mice exhibited enhanced hypertension and aortic hypertrophy. αCGRP gene expression was increased in dorsal root ganglia and at the conduit and resistance vessel level of wild-type mice at both time points. βCGRP gene expression was also observed and shown to be linked to plasma levels of CGRP. Mesenteric artery contractile and relaxant responses in vitro and endothelial NO synthase expression were similar in all groups. The aorta exhibited vascular hypertrophy, increased collagen formation, and oxidant stress markers in response to angiotensin II, with highest effects observed in αCGRP knockout mice. Gene and protein expression of endothelial NO synthase was lacking in the aortae after angiotensin II treatment, especially in αCGRP knockout mice. These results demonstrate the ongoing upregulation of αCGRP at the levels of both conduit and resistance vessels in vascular tissue in a model of hypertension and the direct association of this with protection against aortic vascular hypertrophy and fibrosis. This upregulation is maintained at a time when expression of aortic endothelial NO synthase and antioxidant defense genes have subsided, in keeping with the concept that the protective influence of αCGRP in hypertension may have been previously underestimated.

  4. Engineering clinically relevant volumes of vascularized bone.

    PubMed

    Roux, Brianna M; Cheng, Ming-Huei; Brey, Eric M

    2015-05-01

    Vascularization remains one of the most important challenges that must be overcome for tissue engineering to be consistently implemented for reconstruction of large volume bone defects. An extensive vascular network is needed for transport of nutrients, waste and progenitor cells required for remodelling and repair. A variety of tissue engineering strategies have been investigated in an attempt to vascularize tissues, including those applying cells, soluble factor delivery strategies, novel design and optimization of bio-active materials, vascular assembly pre-implantation and surgical techniques. However, many of these strategies face substantial barriers that must be overcome prior to their ultimate translation into clinical application. In this review recent progress in engineering vascularized bone will be presented with an emphasis on clinical feasibility.

  5. Engineering clinically relevant volumes of vascularized bone

    PubMed Central

    Roux, Brianna M; Cheng, Ming-Huei; Brey, Eric M

    2015-01-01

    Vascularization remains one of the most important challenges that must be overcome for tissue engineering to be consistently implemented for reconstruction of large volume bone defects. An extensive vascular network is needed for transport of nutrients, waste and progenitor cells required for remodelling and repair. A variety of tissue engineering strategies have been investigated in an attempt to vascularize tissues, including those applying cells, soluble factor delivery strategies, novel design and optimization of bio-active materials, vascular assembly pre-implantation and surgical techniques. However, many of these strategies face substantial barriers that must be overcome prior to their ultimate translation into clinical application. In this review recent progress in engineering vascularized bone will be presented with an emphasis on clinical feasibility. PMID:25877690

  6. Plant Vascular Biology 2013: vascular trafficking.

    PubMed

    Ursache, Robertas; Heo, Jung-Ok; Helariutta, Ykä

    2014-04-01

    About 200 researchers from around the world attended the Third International Conference on Plant Vascular Biology (PVB 2013) held in July 2013 at the Rantapuisto Conference Center, in Helsinki, Finland (http://www.pvb2013.org). The plant vascular system, which connects every organ in the mature plant, continues to attract the interest of researchers representing a wide range of disciplines, including development, physiology, systems biology, and computational biology. At the meeting, participants discussed the latest research advances in vascular development, long- and short-distance vascular transport and long-distance signalling in plant defence, in addition to providing a context for how these studies intersect with each other. The meeting provided an opportunity for researchers working across a broad range of fields to share ideas and to discuss future directions in the expanding field of vascular biology. In this report, the latest advances in understanding the mechanism of vascular trafficking presented at the meeting have been summarized.

  7. Branding of vascular surgery.

    PubMed

    Perler, Bruce A

    2008-03-01

    The Society for Vascular Surgery surveyed primary care physicians (PCPs) to understand how PCPs make referral decisions for their patients with peripheral vascular disease. Responses were received from 250 PCPs in 44 states. More than 80% of the respondents characterized their experiences with vascular surgeons as positive or very positive. PCPs perceive that vascular surgeons perform "invasive" procedures and refer patients with the most severe vascular disease to vascular surgeons but were more than twice as likely to refer patients to cardiologists, believing they are better able to perform minimally invasive procedures. Nevertheless, PCPs are receptive to the notion of increasing referrals to vascular surgeons. A successful branding campaign will require considerable education of referring physicians about the totality of traditional vascular and endovascular care increasingly provided by the contemporary vascular surgical practice and will be most effective at the local grassroots level.

  8. [Hair shaft abnormalities].

    PubMed

    Itin, P H; Düggelin, M

    2002-05-01

    Hair shaft disorders may lead to brittleness and uncombable hair. In general the hair feels dry and lusterless. Hair shaft abnormalities may occur as localized or generalized disorders. Genetic predisposition or exogenous factors are able to produce and maintain hair shaft abnormalities. In addition to an extensive history and physical examination the most important diagnostic examination to analyze a hair shaft problem is light microscopy. Therapy of hair shaft disorders should focus to the cause. In addition, minimizing traumatic influences to hair shafts, such as dry hair with an electric dryer, permanent waves and dyes is important. A short hair style is more suitable for such patients with hair shaft disorders.

  9. Vascular gene expression: a hypothesis

    PubMed Central

    Martínez-Navarro, Angélica C.; Galván-Gordillo, Santiago V.; Xoconostle-Cázares, Beatriz; Ruiz-Medrano, Roberto

    2013-01-01

    The phloem is the conduit through which photoassimilates are distributed from autotrophic to heterotrophic tissues and is involved in the distribution of signaling molecules that coordinate plant growth and responses to the environment. Phloem function depends on the coordinate expression of a large array of genes. We have previously identified conserved motifs in upstream regions of the Arabidopsis genes, encoding the homologs of pumpkin phloem sap mRNAs, displaying expression in vascular tissues. This tissue-specific expression in Arabidopsis is predicted by the overrepresentation of GA/CT-rich motifs in gene promoters. In this work we have searched for common motifs in upstream regions of the homologous genes from plants considered to possess a “primitive” vascular tissue (a lycophyte), as well as from others that lack a true vascular tissue (a bryophyte), and finally from chlorophytes. Both lycophyte and bryophyte display motifs similar to those found in Arabidopsis with a significantly low E-value, while the chlorophytes showed either a different conserved motif or no conserved motif at all. These results suggest that these same genes are expressed coordinately in non-vascular plants; this coordinate expression may have been one of the prerequisites for the development of conducting tissues in plants. We have also analyzed the phylogeny of conserved proteins that may be involved in phloem function and development. The presence of CmPP16, APL, FT, and YDA in chlorophytes suggests the recruitment of ancient regulatory networks for the development of the vascular tissue during evolution while OPS is a novel protein specific to vascular plants. PMID:23882276

  10. Methods and systems for detecting abnormal digital traffic

    DOEpatents

    Goranson, Craig A [Kennewick, WA; Burnette, John R [Kennewick, WA

    2011-03-22

    Aspects of the present invention encompass methods and systems for detecting abnormal digital traffic by assigning characterizations of network behaviors according to knowledge nodes and calculating a confidence value based on the characterizations from at least one knowledge node and on weighting factors associated with the knowledge nodes. The knowledge nodes include a characterization model based on prior network information. At least one of the knowledge nodes should not be based on fixed thresholds or signatures. The confidence value includes a quantification of the degree of confidence that the network behaviors constitute abnormal network traffic.

  11. Pathogenesis of diabetic cerebral vascular disease complication

    PubMed Central

    Xu, Ren-Shi

    2015-01-01

    Diabetes mellitus is one of the most potent independent risk factors for the development of diabetic cerebral vascular disease (CVD). Many evidences suggested that hyperglycemia caused excess free fatty acids, the loss of endothelium-derived nitric oxide, insulin resistance, the prothrombotic state, endothelial dysfunction, the abnormal release of endothelial vasoactivators, vascular smooth muscle dysfunction, oxidative stress, and the downregulation of miRs participated in vessel generation and recovery as well as the balance of endotheliocytes. In turn, these abnormalities, mainly via phosphatidylinositol 3 kinase, mitogen-activated protein kinase, polyol, hexosamine, protein kinase C activation, and increased generation of advanced glycosylation end products pathway, play an important role in inducing diabetic CVD complication. A deeper comprehension of pathogenesis producing diabetic CVD could offer base for developing new therapeutic ways preventing diabetic CVD complications, therefore, in the paper we mainly reviewed present information about the possible pathogenesis of diabetic CVD complication. PMID:25685278

  12. Collagen vascular disease

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/001223.htm Collagen vascular disease To use the sharing features on ... were previously said to have "connective tissue" or "collagen vascular" disease. We now have names for many ...

  13. Clinicopathologic abnormalities associated with snake envenomation in domestic animals.

    PubMed

    Goddard, Amelia; Schoeman, Johan P; Leisewitz, Andrew L; Nagel, Salome S; Aroch, Itamar

    2011-09-01

    Envenomation of domestic animals by snakes occurs frequently in certain geographic areas. However, reports describing clinical signs, clinicopathologic abnormalities, therapeutic approaches, and outcomes are sparse. This review summarizes various snake families, venom types associated with harmful snakes, and the significant hematologic, hemostatic, and biochemical abnormalities associated with envenomation. Hematologic abnormalities include RBC membrane abnormalities, hemolysis, hemoconcentration, leukogram changes, and platelet abnormalities, specifically thrombocytopenia. Coagulopathies associated with snake envenomation are well described in human medicine, and many studies have demonstrated properties of venoms that lead to both procoagulation and anticoagulation. As expected, similar abnormalities have been described in domestic animals. Biochemical abnormalities are associated with the effects of venom on tissues such as liver, skeletal and cardiac muscle, vascular endothelium, and kidney as well as effects on protein components and cholesterol. This comprehensive review of clinicopathologic abnormalities associated with envenomation and their relationships to characterized venom constituents should be useful both in the diagnosis and management of envenomation and should serve as a foundation for future research in this field.

  14. Effects of vascularization on cancer nanochemotherapy outcomes

    NASA Astrophysics Data System (ADS)

    Paiva, L. R.; Ferreira, S. C.; Martins, M. L.

    2016-08-01

    Cancer therapy requires anticancer agents capable of efficient and uniform systemic delivery. One promising route to their development is nanotechnology. Here, a previous model for cancer chemotherapy based on a nanosized drug carrier (Paiva et al., 2011) is extended by including tissue vasculature and a three-dimensional growth. We study through computer simulations the therapy against tumors demanding either large or small nutrient supplies growing under different levels of tissue vascularization. Our results indicate that highly vascularized tumors demand more aggressive therapies (larger injected doses administrated at short intervals) than poorly vascularized ones. Furthermore, nanoparticle endocytic rate by tumor cells, not its selectivity, is the major factor that determines the therapeutic success. Finally, our finds indicate that therapies combining cytotoxic agents with antiangiogenic drugs that reduce the abnormal tumor vasculature, instead of angiogenic drugs that normalize it, can lead to successful treatments using feasible endocytic rates and administration intervals.

  15. Regulatory Circuits Controlling Vascular Cell Calcification

    PubMed Central

    Sallam, Tamer; Cheng, Henry; Demer, Linda L.; Tintut, Yin

    2013-01-01

    Vascular calcification is a common feature of chronic kidney disease, cardiovascular disease, and aging. Such abnormal calcium deposition occurs in medial and/or intimal layers of blood vessels as well as in cardiac valves. Once considered a passive and inconsequential finding, the presence of calcium deposits in the vasculature is widely accepted as a predictor of increased morbidity and mortality. Recognition of the importance of vascular calcification in health is driving research into mechanisms that govern its development, progression, and regression. Diverse, but highly interconnected factors, have been implicated, including disturbances in lipid metabolism, oxidative stress, inflammatory cytokines, and mineral and hormonal balances, which can lead to formation of osteoblast-like cells in the artery wall. A tight balance of procalcific and anticalcific regulators dictates the extent of disease. In this review, we focus on the main regulatory circuits modulating vascular cell calcification. PMID:23269436

  16. Neurogenic vascular headaches, food and chemical triggers.

    PubMed

    Trotsky, M B

    1994-04-01

    Recent evidence has demonstrated that neurogenic vascular headaches are a combination of neurological primary events and secondary vasomotor changes. The neurological events involve the hypothalamus and sensory cortex with sympathetic hypofunction and noradrenergic abnormalities. A platelet theory has been proposed but has not really been confirmed as a legitimate cause of the neurogenic vascular headaches. Food and chemicals in foods can act as a precipitating factor in the food-sensitive neurogenic vascular headache patient. In these patients evidence is now being demonstrated to confirm this, but larger patient studies are needed. The food-sensitive migraine patient and cluster headache patient must give a good history and food diary to go along with active challenges and provocative testing in order to determine the causative foods. Any concomitant allergies of inhalants or environmentals must also be treated. The treatment modalities of elimination and rotation diets or provocation neutralization may successfully control the headaches without the need for continuous medications.

  17. Photoacoustic tomography of vascular therapy in a preclinical mouse model of colorectal carcinoma

    NASA Astrophysics Data System (ADS)

    Johnson, S. P.; Ogunlade, O.; Zhang, E.; Laufer, J.; Rajkumar, V.; Pedley, R. B.; Beard, P.

    2014-03-01

    Vascular therapy in oncology exploits the differences between normal blood vessels and abnormal tumour neoangiogenesis to selectively target cancer. For optimal treatment efficacy, and translation of novel compounds, the response of the tumour vasculature needs to be assessed. Photoacoustic tomography (PAT) is capable of this as it provides highly spatially resolved 3D images of vascular networks in biological tissue to cm depths. In preclinical models of cancer this is sufficient to encompass entire subcutaneous tumours, and can therefore be used to evaluate pharmacological intervention directed at the vasculature. In this study the vascular disrupting agent OXi4503 was used to treat subcutaneous tumour mouse models of two human colorectal carcinoma tumour types (SW1222, LS174T) at a range of concentrations (40mg/kg, 10mg/kg, 1mg/kg and sham dose control). The characteristic destruction of tumour vasculature caused by OXi4503 was observed by PAT and confirmed ex vivo via histology. Differences observed between the two tumour types assessed demonstrate the importance of tumour microenvironment and pathophysiology on response to therapy. Differential response to different doses of OXi4503 was observed, with outward tumour growth only seen once entire tumour viability had been re-established; this demonstrates the potential of PAT to act as a biomarker of response for the translation of novel anti-vascular compounds and also within the clinic. This study shows clearly that PAT can accurately assess the time course of drug action and relapse of pharmacodynamic effect in preclinical models of cancer and the important translational prospects for vascular targeted tumour therapies.

  18. Tissue Engineering Special Feature: A macroporous hydrogel for the coculture of neural progenitor and endothelial cells to form functional vascular networks in vivo

    NASA Astrophysics Data System (ADS)

    Ford, Millicent C.; Bertram, James P.; Royce Hynes, Sara; Michaud, Michael; Li, Qi; Young, Michael; Segal, Steven S.; Madri, Joseph A.; Lavik, Erin B.

    2006-02-01

    A microvascular network is critical for the survival and function of most tissues. We have investigated the potential of neural progenitor cells to augment the formation and stabilization of microvascular networks in a previously uncharacterized three-dimensional macroporous hydrogel and the ability of this engineered system to develop a functional microcirculation in vivo. The hydrogel is synthesized by cross-linking polyethylene glycol with polylysine around a salt-leached polylactic-co-glycolic acid scaffold that is degraded in a sodium hydroxide solution. An open macroporous network is formed that supports the efficient formation of tubular structures by brain endothelial cells. After subcutaneous implantation of hydrogel cocultures in mice, blood flow in new microvessels was apparent at 2 weeks with perfused networks established on the surface of implants at 6 weeks. Compared to endothelial cells cultured alone, cocultures of endothelial cells and neural progenitor cells had a significantly greater density of tubular structures positive for platelet endothelial cell adhesion molecule-1 at the 6-week time point. In implant cross sections, the presence of red blood cells in vessel lumens confirmed a functional microcirculation. These findings indicate that neural progenitor cells promote the formation of endothelial cell tubes in coculture and the development of a functional microcirculation in vivo. We demonstrate a previously undescribed strategy for creating stable microvascular networks to support engineered tissues of desired parenchymal cell origin. microvasculature | neural stem cells | polymer | scaffold

  19. Craniofacial abnormalities in Hutchinson-Gilford progeria syndrome.

    PubMed

    Ullrich, N J; Silvera, V M; Campbell, S E; Gordon, L B

    2012-09-01

    HGPS is a rare syndrome of segmental premature aging. Our goal was to expand the scope of structural bone and soft-tissue craniofacial abnormalities in HGPS through CT or MR imaging. Using The Progeria Research Foundation Medical and Research Database, 98 imaging studies on 25 patients, birth to 14.1 years of age, were comprehensively reviewed. Eight newly identified abnormalities involving the calvaria, skull base, and soft tissues of the face and orbits were present with prevalences between 43% and 100%. These included J-shaped sellas, a mottled appearance and increased vascular markings of the calvaria, abnormally configured mandibular condyles, hypoplastic articular eminences, small zygomatic arches, prominent parotid glands, and optic nerve kinking. This expanded craniofacial characterization helps link disease features and improves our ability to evaluate how underlying genetic and cellular abnormalities culminate in a disease phenotype.

  20. Morphological abnormalities in elasmobranchs.

    PubMed

    Moore, A B M

    2015-08-01

    A total of 10 abnormal free-swimming (i.e., post-birth) elasmobranchs are reported from The (Persian-Arabian) Gulf, encompassing five species and including deformed heads, snouts, caudal fins and claspers. The complete absence of pelvic fins in a milk shark Rhizoprionodon acutus may be the first record in any elasmobranch. Possible causes, including the extreme environmental conditions and the high level of anthropogenic pollution particular to The Gulf, are briefly discussed.

  1. Vascular restoration therapy and bioresorbable vascular scaffold

    PubMed Central

    Wang, Yunbing; Zhang, Xingdong

    2014-01-01

    This article describes the evolution of minimally invasive intervention technologies for vascular restoration therapy from early-stage balloon angioplasty in 1970s, metallic bare metal stent and metallic drug-eluting stent technologies in 1990s and 2000s, to bioresorbable vascular scaffold (BVS) technology in large-scale development in recent years. The history, the current stage, the challenges and the future of BVS development are discussed in detail as the best available approach for vascular restoration therapy. The criteria of materials selection, design and processing principles of BVS, and the corresponding clinical trial results are also summarized in this article. PMID:26816624

  2. Multifocal vascular lesions.

    PubMed

    Levin, Laura E; Lauren, Christine T

    2016-03-01

    Multifocal vascular lesions are important to recognize and appropriately diagnose. Generally first noticed on the skin, multifocal vascular lesions may have systemic involvement. Distinguishing among the different types of multifocal vascular lesions is often based on clinical features; however, radiological imaging and/or biopsy are frequently needed to identify distinct features and guide treatment. Knowledge of the systemic associations that can occur with different vascular anomalies may reduce life-threatening complications, such as coagulopathy, bleeding, cardiac compromise, and neurologic sequelae. This review provides a synopsis of the epidemiology, pathogenesis, presentation, workup, and treatment of several well-recognized multifocal vascular tumors and malformations. PMID:27607324

  3. Initiation of vascular development.

    PubMed

    Ohashi-Ito, Kyoko; Fukuda, Hiroo

    2014-06-01

    The initiation of vascular development occurs during embryogenesis and the development of lateral organs, such as lateral roots and leaves. Understanding the mechanism underlying the initiation of vascular development has been an important goal of plant biologists. Auxin flow is a crucial factor involved in the initiation of vascular development. In addition, recent studies have identified key factors that regulate the establishment of vascular initial cells in embryos and roots. In this review, we summarize the recent findings in this field and discuss the initiation of vascular development.

  4. Chromosome abnormalities in glioma

    SciTech Connect

    Li, Y.S.; Ramsay, D.A.; Fan, Y.S.

    1994-09-01

    Cytogenetic studies were performed in 25 patients with gliomas. An interesting finding was a seemingly identical abnormality, an extra band on the tip of the short arm of chromosome 1, add(1)(p36), in two cases. The abnormality was present in all cells from a patient with a glioblastoma and in 27% of the tumor cells from a patient with a recurrent irradiated anaplastic astrocytoma; in the latter case, 7 unrelated abnormal clones were identified except 4 of those clones shared a common change, -Y. Three similar cases have been described previously. In a patient with pleomorphic astrocytoma, the band 1q42 in both homologues of chromosome 1 was involved in two different rearrangements. A review of the literature revealed that deletion of the long arm of chromosome 1 including 1q42 often occurs in glioma. This may indicate a possible tumor suppressor gene in this region. Cytogenetic follow-up studies were carried out in two patients and emergence of unrelated clones were noted in both. A total of 124 clonal breakpoints were identified in the 25 patients. The breakpoints which occurred three times or more were: 1p36, 1p22, 1q21, 1q25, 3q21, 7q32, 8q22, 9q22, 16q22, and 22q13.

  5. [Congenital foot abnormalities].

    PubMed

    Delpont, M; Lafosse, T; Bachy, M; Mary, P; Alves, A; Vialle, R

    2015-03-01

    The foot may be the site of birth defects. These abnormalities are sometimes suspected prenatally. Final diagnosis depends on clinical examination at birth. These deformations can be simple malpositions: metatarsus adductus, talipes calcaneovalgus and pes supinatus. The prognosis is excellent spontaneously or with a simple orthopedic treatment. Surgery remains outstanding. The use of a pediatric orthopedist will be considered if malposition does not relax after several weeks. Malformations (clubfoot, vertical talus and skew foot) require specialized care early. Clubfoot is characterized by an equine and varus hindfoot, an adducted and supine forefoot, not reducible. Vertical talus combines equine hindfoot and dorsiflexion of the forefoot, which is performed in the midfoot instead of the ankle. Skew foot is suspected when a metatarsus adductus is resistant to conservative treatment. Early treatment is primarily orthopedic at birth. Surgical treatment begins to be considered after walking age. Keep in mind that an abnormality of the foot may be associated with other conditions: malposition with congenital hip, malformations with syndromes, neurological and genetic abnormalities. PMID:25524290

  6. Abnormal pressures as hydrodynamic phenomena

    USGS Publications Warehouse

    Neuzil, C.E.

    1995-01-01

    So-called abnormal pressures, subsurface fluid pressures significantly higher or lower than hydrostatic, have excited speculation about their origin since subsurface exploration first encountered them. Two distinct conceptual models for abnormal pressures have gained currency among earth scientists. The static model sees abnormal pressures generally as relict features preserved by a virtual absence of fluid flow over geologic time. The hydrodynamic model instead envisions abnormal pressures as phenomena in which flow usually plays an important role. This paper develops the theoretical framework for abnormal pressures as hydrodynamic phenomena, shows that it explains the manifold occurrences of abnormal pressures, and examines the implications of this approach. -from Author

  7. Amaurosis fugax associated with congenital vascular defect

    PubMed Central

    Giltner, John W; Thomas, Edward R; Rundell, William K

    2016-01-01

    A 68-year-old female with no significant past medical history presented with loss of vision in the lower half of her left eye that lasted <5 minutes. No abnormalities were found on ocular or physical exam. Computed tomography angiography and carotid ultrasound were performed, which confirmed the diagnosis as amaurosis fugax with two abnormalities leading to the transient retinal vessel occlusion. First, it was found that the patient has a congenital vascular anomaly, which consisted most notably of a right-sided aortic arch. This vascular anomaly also consisted of abnormal branching of the left subclavian and common carotid arteries, predisposing the patient to turbulent blood flow and increased risk of the formation of an atherosclerotic plaque at the origin of the common carotid artery. This is an abnormal location for a plaque leading to amaurosis fugax compared to the most common location at the carotid bifurcation. Endarterectomy was not performed because of the difficult location of the plaque and tortuosity of the vessel. Rather, medical intervention with antiplatelet and lipid-lowering therapy was initiated to lower the risk of future retinal or cerebral thromboembolic events. PMID:27445507

  8. Vascularization in bone tissue engineering constructs

    PubMed Central

    Mercado-Pagán, Ángel E.; Stahl, Alexander M.; Shanjani, Yaser; Yang, Yunzhi

    2016-01-01

    Vascularization of large bone grafts is one of the main challenges of bone tissue engineering (BTE), and has held back the clinical translation of engineered bone constructs for two decades so far. The ultimate goal of vascularized BTE constructs is to provide a bone environment rich in functional vascular networks to achieve efficient osseointegration and accelerate restoration of function after implantation. To attain both structural and vascular integration of the grafts, a large number of biomaterials, cells, and biological cues have been evaluated. This review will present biological considerations for bone function restoration, contemporary approaches for clinical salvage of large bone defects and their limitations, state-of-the-art research on the development of vascularized bone constructs, and perspectives on evaluating and implementing novel BTE grafts in clinical practice. Success will depend on achieving full graft integration at multiple hierarchical levels, both between the individual graft components as well as between the implanted constructs and their surrounding host tissues. The paradigm of vascularized tissue constructs could not only revolutionize the progress of bone tissue engineering, but could also be readily applied to other fields in regenerative medicine for the development of new innovative vascularized tissue designs. PMID:25616591

  9. Feeling Abnormal: Simulation of Deviancy in Abnormal and Exceptionality Courses.

    ERIC Educational Resources Information Center

    Fernald, Charles D.

    1980-01-01

    Describes activity in which student in abnormal psychology and psychology of exceptional children classes personally experience being judged abnormal. The experience allows the students to remember relevant research, become sensitized to the feelings of individuals classified as deviant, and use caution in classifying individuals as abnormal.…

  10. Abnormal human sex chromosome constitutions

    SciTech Connect

    1993-12-31

    Chapter 22, discusses abnormal human sex chromosome constitution. Aneuploidy of X chromosomes with a female phenotype, sex chromosome aneuploidy with a male phenotype, and various abnormalities in X chromosome behavior are described. 31 refs., 2 figs.

  11. Exercises to Improve Gait Abnormalities

    MedlinePlus

    ... Home About iChip Articles Directories Videos Resources Contact Exercises to Improve Gait Abnormalities Home » Article Categories » Exercise and Fitness Font Size: A A A A Exercises to Improve Gait Abnormalities Next Page The manner ...

  12. Vascular endothelial growth factor receptor-2 promotes the development of the lymphatic vasculature.

    PubMed

    Dellinger, Michael T; Meadows, Stryder M; Wynne, Katherine; Cleaver, Ondine; Brekken, Rolf A

    2013-01-01

    Vascular endothelial growth factor receptor 2 (VEGFR2) is highly expressed by lymphatic endothelial cells and has been shown to stimulate lymphangiogenesis in adult mice. However, the role VEGFR2 serves in the development of the lymphatic vascular system has not been defined. Here we use the Cre-lox system to show that the proper development of the lymphatic vasculature requires VEGFR2 expression by lymphatic endothelium. We show that Lyve-1(wt/Cre);Vegfr2(flox/flox) mice possess significantly fewer dermal lymphatic vessels than Vegfr2(flox/flox) mice. Although Lyve-1(wt/Cre);Vegfr2(flox/flox) mice exhibit lymphatic hypoplasia, the lymphatic network is functional and contains all of the key features of a normal lymphatic network (initial lymphatic vessels and valved collecting vessels surrounded by smooth muscle cells (SMCs)). We also show that Lyve-1(Cre) mice display robust Cre activity in macrophages and in blood vessels in the yolk sac, liver and lung. This activity dramatically impairs the development of blood vessels in these tissues in Lyve-1(wt/Cre);Vegfr2(flox/flox) embryos, most of which die after embryonic day14.5. Lastly, we show that inactivation of Vegfr2 in the myeloid lineage does not affect the development of the lymphatic vasculature. Therefore, the abnormal lymphatic phenotype of Lyve-1(wt/Cre);Vegfr2(flox/flox) mice is due to the deletion of Vegfr2 in the lymphatic vasculature not macrophages. Together, this work demonstrates that VEGFR2 directly promotes the expansion of the lymphatic network and further defines the molecular mechanisms controlling the development of the lymphatic vascular system.

  13. Abnormal ionization in sonoluminescence

    NASA Astrophysics Data System (ADS)

    Zhang, Wen-Juan; An, Yu

    2015-04-01

    Sonoluminescence is a complex phenomenon, the mechanism of which remains unclear. The present study reveals that an abnormal ionization process is likely to be present in the sonoluminescing bubble. To fit the experimental data of previous studies, we assume that the ionization energies of the molecules and atoms in the bubble decrease as the gas density increases and that the decrease of the ionization energy reaches about 60%-70% as the bubble flashes, which is difficult to explain by using previous models. Project supported by the Research Fund for the Doctoral Program of Higher Education of China (Grant No. 20120002110031) and the National Natural Science Foundation of China (Grant No. 11334005).

  14. Constructal vascularized structures

    NASA Astrophysics Data System (ADS)

    Cetkin, Erdal

    2015-06-01

    Smart features such as self-healing and selfcooling require bathing the entire volume with a coolant or/and healing agent. Bathing the entire volume is an example of point to area (or volume) flows. Point to area flows cover all the distributing and collecting kinds of flows, i.e. inhaling and exhaling, mining, river deltas, energy distribution, distribution of products on the landscape and so on. The flow resistances of a point to area flow can be decreased by changing the design with the guidance of the constructal law, which is the law of the design evolution in time. In this paper, how the flow resistances (heat, fluid and stress) can be decreased by using the constructal law is shown with examples. First, the validity of two assumptions is surveyed: using temperature independent Hess-Murray rule and using constant diameter ducts where the duct discharges fluid along its edge. Then, point to area types of flows are explained by illustrating the results of two examples: fluid networks and heating an area. Last, how the structures should be vascularized for cooling and mechanical strength is documented. This paper shows that flow resistances can be decreased by morphing the shape freely without any restrictions or generic algorithms.

  15. Critical Endothelial Regulation by LRP5 during Retinal Vascular Development.

    PubMed

    Huang, Wei; Li, Qing; Amiry-Moghaddam, Mahmood; Hokama, Madoka; Sardi, Sylvia H; Nagao, Masashi; Warman, Matthew L; Olsen, Bjorn R

    2016-01-01

    Vascular abnormalities in the eye are the leading cause of many forms of inherited and acquired human blindness. Loss-of-function mutations in the Wnt-binding co-receptor LRP5 leads to aberrant ocular vascularization and loss of vision in genetic disorders such as osteoporosis-pseudoglioma syndrome. The canonical Wnt-β-catenin pathway is known to regulate retinal vascular development. However, it is unclear what precise role LPR5 plays in this process. Here, we show that loss of LRP5 function in mice causes retinal hypovascularization during development as well as retinal neovascularization in adulthood with disorganized and leaky vessels. Using a highly specific Flk1-CreBreier line for vascular endothelial cells, together with several genetic models, we demonstrate that loss of endothelium-derived LRP5 recapitulates the retinal vascular defects in Lrp5-/- mice. In addition, restoring LRP5 function only in endothelial cells in Lrp5-/- mice rescues their retinal vascular abnormalities. Furthermore, we show that retinal vascularization is regulated by LRP5 in a dosage dependent manner and does not depend on LRP6. Our study provides the first direct evidence that endothelium-derived LRP5 is both necessary and sufficient to mediate its critical role in the development and maintenance of retinal vasculature. PMID:27031698

  16. Critical Endothelial Regulation by LRP5 during Retinal Vascular Development

    PubMed Central

    Huang, Wei; Li, Qing; Amiry-Moghaddam, Mahmood; Hokama, Madoka; Sardi, Sylvia H.; Nagao, Masashi; Warman, Matthew L.; Olsen, Bjorn R.

    2016-01-01

    Vascular abnormalities in the eye are the leading cause of many forms of inherited and acquired human blindness. Loss-of-function mutations in the Wnt-binding co-receptor LRP5 leads to aberrant ocular vascularization and loss of vision in genetic disorders such as osteoporosis-pseudoglioma syndrome. The canonical Wnt-β-catenin pathway is known to regulate retinal vascular development. However, it is unclear what precise role LPR5 plays in this process. Here, we show that loss of LRP5 function in mice causes retinal hypovascularization during development as well as retinal neovascularization in adulthood with disorganized and leaky vessels. Using a highly specific Flk1-CreBreier line for vascular endothelial cells, together with several genetic models, we demonstrate that loss of endothelium-derived LRP5 recapitulates the retinal vascular defects in Lrp5-/- mice. In addition, restoring LRP5 function only in endothelial cells in Lrp5-/- mice rescues their retinal vascular abnormalities. Furthermore, we show that retinal vascularization is regulated by LRP5 in a dosage dependent manner and does not depend on LRP6. Our study provides the first direct evidence that endothelium-derived LRP5 is both necessary and sufficient to mediate its critical role in the development and maintenance of retinal vasculature. PMID:27031698

  17. Abnormal hematological indices in cirrhosis

    PubMed Central

    Qamar, Amir A; Grace, Norman D

    2009-01-01

    Abnormalities in hematological indices are frequently encountered in cirrhosis. Multiple causes contribute to the occurrence of hematological abnormalities. Recent studies suggest that the presence of hematological cytopenias is associated with a poor prognosis in cirrhosis. The present article reviews the pathogenesis, incidence, prevalence, clinical significance and treatment of abnormal hematological indices in cirrhosis. PMID:19543577

  18. Adult neurogenesis and the vascular Nietzsche.

    PubMed

    Palmer, Theo D

    2002-06-13

    Adult neurogenesis is mediated by immature neural precursors that divide within the residual germinal matrices of the brain. In the paper by in this issue of Neuron, the "cause and effect" of adult neurogenesis takes a major step forward with the description of a vascular signaling network that influences neuronal precursor migration and fate.

  19. [Microscopic anatomy of abnormal structure in root tuber of Pueraria lobata].

    PubMed

    Duan, Hai-yan; Cheng, Ming-en; Peng, Hua-sheng; Zhang, He-ting; Zhao, Yu-jiao

    2015-11-01

    Puerariae Lobatae Radix, also known as Gegen, is a root derived from Pueraria lobata. Based on field investigation and the developmental anatomy of root tuber, we have elucidated the relationship between the growth of root tuber and the anomalous structure. The results of analysis showed that the root system of P. lobata was developed from seed and adventitious root and there existed root tuber, adventitious root and conductive root according to morphology and function. The root tuber was developed from adventitious root, its secondary structure conformed to the secondary structure of dicotyledon's root. With the development of root, the secondary phloem of root tuber appeared abnormal vascular tissue, which was distributed like ring in the outside of secondary vascular tissue. The root tuber might have 4-6 concentric circular permutation abnormal vascular tissuelobate, and was formed by the internal development of abnormal vascular tissue. The xylem and phloem of abnormal vascular tissue were the main body of the root tuber. The results reveal the abnormal anatomical structure development of P. lobata, also provides the theoretical basis for reasonable harvest medicinal parts and promoting sustainable utilization of resources of P. lobata.

  20. [Microscopic anatomy of abnormal structure in root tuber of Pueraria lobata].

    PubMed

    Duan, Hai-yan; Cheng, Ming-en; Peng, Hua-sheng; Zhang, He-ting; Zhao, Yu-jiao

    2015-11-01

    Puerariae Lobatae Radix, also known as Gegen, is a root derived from Pueraria lobata. Based on field investigation and the developmental anatomy of root tuber, we have elucidated the relationship between the growth of root tuber and the anomalous structure. The results of analysis showed that the root system of P. lobata was developed from seed and adventitious root and there existed root tuber, adventitious root and conductive root according to morphology and function. The root tuber was developed from adventitious root, its secondary structure conformed to the secondary structure of dicotyledon's root. With the development of root, the secondary phloem of root tuber appeared abnormal vascular tissue, which was distributed like ring in the outside of secondary vascular tissue. The root tuber might have 4-6 concentric circular permutation abnormal vascular tissuelobate, and was formed by the internal development of abnormal vascular tissue. The xylem and phloem of abnormal vascular tissue were the main body of the root tuber. The results reveal the abnormal anatomical structure development of P. lobata, also provides the theoretical basis for reasonable harvest medicinal parts and promoting sustainable utilization of resources of P. lobata. PMID:27097408

  1. Differential miRNA Expression in Cells and Matrix Vesicles in Vascular Smooth Muscle Cells from Rats with Kidney Disease

    PubMed Central

    Chaturvedi, Praneet; Chen, Neal X.; O’Neill, Kalisha; McClintick, Jeanette N.; Moe, Sharon M.; Janga, Sarath Chandra

    2015-01-01

    Vascular calcification is a complex process and has been associated with aging, diabetes, chronic kidney disease (CKD). Although there have been several studies that examine the role of miRNAs (miRs) in bone osteogenesis, little is known about the role of miRs in vascular calcification and their role in the pathogenesis of vascular abnormalities. Matrix vesicles (MV) are known to play in important role in initiating vascular smooth muscle cell (VSMC) calcification. In the present study, we performed miRNA microarray analysis to identify the dysregulated miRs between MV and VSMC derived from CKD rats to understand the role of post-transcriptional regulatory networks governed by these miRNAs in vascular calcification and to uncover the differential miRNA content of MV. The percentage of miRNA to total RNA was increased in MV compared to VSMC. Comparison of expression profiles of miRNA by microarray demonstrated 33 miRs to be differentially expressed with the majority (~ 57%) of them down-regulated. Target genes controlled by differentially expressed miRNAs were identified utilizing two different complementary computational approaches Miranda and Targetscan to understand the functions and pathways that may be affected due to the production of MV from calcifying VSMC thereby contributing to the regulation of genes by miRs. We found several processes including vascular smooth muscle contraction, response to hypoxia and regulation of muscle cell differentiation to be enriched. Signaling pathways identified included MAP-kinase and wnt signaling that have previously been shown to be important in vascular calcification. In conclusion, our results demonstrate that miRs are concentrated in MV from calcifying VSMC, and that important functions and pathways are affected by the miRs dysregulation between calcifying VSMC and the MV they produce. This suggests that miRs may play a very important regulatory role in vascular calcification in CKD by controlling an extensive network

  2. Imaging Pediatric Vascular Lesions

    PubMed Central

    Nguyen, Tuyet A.; Krakowski, Andrew C.; Naheedy, John H.; Kruk, Peter G.

    2015-01-01

    Vascular anomalies are commonly encountered in pediatric and dermatology practices. Most of these lesions are benign and easy to diagnose based on history and clinical exam alone. However, in some cases the diagnosis may not be clear. This may be of particular concern given that vascular anomalies may occasionally be associated with an underlying syndrome, congenital disease, or serious, life-threatening condition. Defining the type of vascular lesion early and correctly is particularly important to determine the optimal approach to management and treatment of each patient. The care of pediatric patients often requires collaboration from a multitude of specialties including pediatrics, dermatology, plastic surgery, radiology, ophthalmology, and neurology. Although early characterization of vascular lesions is important, consensus guidelines regarding the evaluation and imaging of vascular anomalies does not exist to date. Here, the authors provide an overview of pediatric vascular lesions, current classification systems for characterizing these lesions, the various imaging modalities available, and recommendations for appropriate imaging evaluation. PMID:26705446

  3. Spirometric abnormalities among welders

    SciTech Connect

    Rastogi, S.K.; Gupta, B.N.; Husain, T.; Mathur, N.; Srivastava, S. )

    1991-10-01

    A group of manual welders age group 13-60 years having a mean exposure period of 12.4 {plus minus} 1.12 years were subjected to spirometry to evaluate the prevalence of spirometric abnormalities. The welders showed a significantly higher prevalence of respiratory impairment than that observed among the unexposed controls as a result of exposure to welding gases which comprised fine particles of lead, zinc, chromium, and manganese. This occurred despite the lower concentration of the pollutants at the work place. In the expose group, the smoking welders showed a prevalence of respiratory impairment significantly higher than that observed in the nonsmoking welders. The results of the pulmonary function tests showed a predominantly restrictive type of pulmonary impairment followed by a mixed ventilatory defect among the welders. The effect of age on pulmonary impairment was not discernible. Welders exposed for over 10 years showed a prevalence of respiratory abnormalities significantly higher than those exposed for less than 10 years. Smoking also had a contributory role.

  4. Vascular Remodeling in Pulmonary Hypertension

    PubMed Central

    Shimoda, Larissa A; Laurie, Steven S.

    2013-01-01

    Pulmonary hypertension is a complex, progressive condition arising from a variety of genetic and pathogenic causes. Patients present with a spectrum of histologic and pathophysiological features, likely reflecting the diversity in underlying pathogenesis. It is widely recognized that structural alterations in the vascular wall contribute to all forms of pulmonary hypertension. Features characteristic of the remodeled vasculature in patients with pulmonary hypertension include increased stiffening of the elastic proximal pulmonary arteries, thickening of the intimal and/or medial layer of muscular arteries, development of vaso-occlusive lesions and the appearance of cells expressing smooth muscle specific markers in normally non-muscular small diameter vessels, resulting from proliferation and migration of pulmonary arterial smooth muscle cells and cellular trans-differentiation. The development of several animal models of pulmonary hypertension has provided the means to explore the mechanistic underpinnings of pulmonary vascular remodeling, although none of the experimental models currently used entirely replicates the pulmonary arterial hypertension observed in patients. Herein, we provide an overview of the histological abnormalities observed in humans with pulmonary hypertension and in preclinical models and discuss insights gained regarding several key signaling pathways contributing to the remodeling process. In particular, we will focus on the roles of ion homeostasis, endothelin-1, serotonin, bone morphogenetic proteins, Rho kinase and hypoxia-inducible factor 1 in pulmonary arterial smooth muscle and endothelial cells, highlighting areas of cross-talk between these pathways and potentials for therapeutic targeting. PMID:23334338

  5. Regionalization of services improves access to emergency vascular surgical care.

    PubMed

    Roche-Nagle, G; Bachynski, K; Nathens, A B; Angoulvant, D; Rubin, B B

    2013-04-01

    Management of vascular surgical emergencies requires rapid access to a vascular surgeon and hospital with the infrastructure necessary to manage vascular emergencies. The purpose of this study was to assess the impact of regionalization of vascular surgery services in Toronto to University Health Network (UHN) and St Michael's Hospital (SMH) on the ability of CritiCall Ontario to transfer patients with life- and limb-threatening vascular emergencies for definitive care. A retrospective review of the CritiCall Ontario database was used to assess the outcome of all calls to CritiCall regarding patients with vascular disease from April 2003 to March 2010. The number of patients with vascular emergencies referred via CritiCall and accepted in transfer by the vascular centers at UHN or SMH increased 500% between 1 April 2003-31 December 2005 and 1 January 2006-31 March 2010. Together, the vascular centers at UHN and SMH accepted 94.8% of the 1002 vascular surgery patients referred via CritiCall from other hospitals between 1 January 2006 and 31 March 2010, and 72% of these patients originated in hospitals outside of the Toronto Central Local Health Integration Network. Across Ontario, the number of physicians contacted before a patient was accepted in transfer fell from 2.9 ± 0.4 before to 1.7 ± 0.3 after the vascular centers opened. In conclusion, the vascular surgery centers at UHN and SMH have become provincial resources that enable the efficient transfer of patients with vascular surgical emergencies from across Ontario. Regionalization of services is a viable model to increase access to emergent care. PMID:23508395

  6. Plant vascular development: from early specification to differentiation.

    PubMed

    De Rybel, Bert; Mähönen, Ari Pekka; Helariutta, Yrjö; Weijers, Dolf

    2016-01-01

    Vascular tissues in plants are crucial to provide physical support and to transport water, sugars and hormones and other small signalling molecules throughout the plant. Recent genetic and molecular studies have identified interconnections among some of the major signalling networks that regulate plant vascular development. Using Arabidopsis thaliana as a model system, these studies enable the description of vascular development from the earliest tissue specification events during embryogenesis to the differentiation of phloem and xylem tissues. Moreover, we propose a model for how oriented cell divisions give rise to a three-dimensional vascular bundle within the root meristem.

  7. Vascular Tissue Engineering: Building Perfusable Vasculature for Implantation

    PubMed Central

    Gui, Liqiong; Niklason, Laura E.

    2014-01-01

    Tissue and organ replacement is required when there are no alternative therapies available. Although vascular tissue engineering was originally developed to meet the clinical demands of small-diameter vascular conduits as bypass grafts, it has evolved into a highly advanced field where perfusable vasculatures are generated for implantation. Herein, we review several cutting-edge techniques that have led to implantable human blood vessels in clinical trials, the novel approaches that build complex perfusable microvascular networks in functional tissues, the use of stem cells to generate endothelial cells for vascularization, as well as the challenges in bringing vascular tissue engineering technologies into the clinics. PMID:24533306

  8. A Rare Stapes Abnormality

    PubMed Central

    Kanona, Hala; Virk, Jagdeep Singh; Kumar, Gaurav; Chawda, Sanjiv; Khalil, Sherif

    2015-01-01

    The aim of this study is to increase awareness of rare presentations, diagnostic difficulties alongside management of conductive hearing loss and ossicular abnormalities. We report the case of a 13-year-old female reporting progressive left-sided hearing loss and high resolution computed tomography was initially reported as normal. Exploratory tympanotomy revealed an absent stapedius tendon and lack of connection between the stapes superstructure and footplate. The footplate was fixed. Stapedotomy and stapes prosthesis insertion resulted in closure of the air-bone gap by 50 dB. A review of world literature was performed using MedLine. Middle ear ossicular discontinuity can result in significant conductive hearing loss. This can be managed effectively with surgery to help restore hearing. However, some patients may not be suitable or decline surgical intervention and can be managed safely conservatively. PMID:25628909

  9. Adult presentation with vascular ring due to double aortic arch.

    PubMed

    Kafka, Henryk; Uebing, Anselm; Mohiaddin, Raad

    2006-11-01

    This is a case report on the use of cardiovascular magnetic resonance imaging to diagnose vascular ring due to double aortic arch in an adult presenting with an abnormal chest X-ray. The experience in this case and the literature review identify the benefits of using cardiovascular magnetic resonance imaging to clarify complex aortic arch anatomy.

  10. Leaf hydraulics II: vascularized tissues.

    PubMed

    Rockwell, Fulton E; Holbrook, N Michele; Stroock, Abraham D

    2014-01-01

    Current models of leaf hydration employ an Ohm's law analogy of the leaf as an ideal capacitor, neglecting the resistance to flow between cells, or treat the leaf as a plane sheet with a source of water at fixed potential filling the mid-plane, neglecting the discrete placement of veins as well as their resistance. We develop a model of leaf hydration that considers the average conductance of the vascular network to a representative areole (region bounded by the vascular network), and represent the volume of tissue within the areole as a poroelastic composite of cells and air spaces. Solutions to the 3D flow problem are found by numerical simulation, and these results are then compared to 1D models with exact solutions for a range of leaf geometries, based on a survey of temperate woody plants. We then show that the hydration times given by these solutions are well approximated by a sum of the ideal capacitor and plane sheet times, representing the time for transport through the vasculature and tissue respectively. We then develop scaling factors relating this approximate solution to the 3D model, and examine the dependence of these scaling factors on leaf geometry. Finally, we apply a similar strategy to reduce the dimensions of the steady state problem, in the context of peristomatal transpiration, and consider the relation of transpirational gradients to equilibrium leaf water potential measurements.

  11. Estrogen, vascular estrogen receptor and hormone therapy in postmenopausal vascular disease.

    PubMed

    Khalil, Raouf A

    2013-12-15

    Cardiovascular disease (CVD) is less common in premenopausal women than men of the same age or postmenopausal women, suggesting vascular benefits of estrogen. Estrogen activates estrogen receptors ERα, ERβ and GPR30 in endothelium and vascular smooth muscle (VSM), which trigger downstream signaling pathways and lead to genomic and non-genomic vascular effects such as vasodilation, decreased VSM contraction and growth and reduced vascular remodeling. However, randomized clinical trials (RCTs), such as the Women's Health Initiative (WHI) and Heart and Estrogen/progestin Replacement Study (HERS), have shown little vascular benefits and even adverse events with menopausal hormone therapy (MHT), likely due to factors related to the MHT used, ER profile, and RCT design. Some MHT forms, dose, combinations or route of administration may have inadequate vascular effects. Age-related changes in ER amount, distribution, integrity and post-ER signaling could alter the vascular response to MHT. The subject's age, preexisting CVD, and hormone environment could also reduce the effects of MHT. Further evaluation of natural and synthetic estrogens, phytoestrogens, and selective estrogen-receptor modulators (SERMs), and the design of appropriate MHT combinations, dose, route and 'timing' could improve the effectiveness of conventional MHT and provide alternative therapies in the peri-menopausal period. Targeting ER using specific ER agonists, localized MHT delivery, and activation of specific post-ER signaling pathways could counter age-related changes in ER. Examination of the hormone environment and conditions associated with hormone imbalance such as polycystic ovary syndrome may reveal the causes of abnormal hormone-receptor interactions. Consideration of these factors in new RCTs such as the Kronos Early Estrogen Prevention Study (KEEPS) could enhance the vascular benefits of estrogen in postmenopausal CVD. PMID:24099797

  12. Estrogen, Vascular Estrogen Receptor and Hormone Therapy in Postmenopausal Vascular Disease

    PubMed Central

    Khalil, Raouf A.

    2013-01-01

    Cardiovascular disease (CVD) is less common in premenopausal women than men of the same age or postmenopausal women, suggesting vascular benefits of estrogen. Estrogen activates estrogen receptors ERα, ERβ and GPR30 in endothelium and vascular smooth muscle (VSM), which trigger downstream signaling pathways and lead to genomic and non-genomic vascular effects such as vasodilation, decreased VSM contraction and growth and reduced vascular remodeling. However, randomized clinical trials (RCTs), such as the Women’s Health Initiative (WHI) and Heart and Estrogen/progestin Replacement Study (HERS), have shown little vascular benefits and even adverse events with menopausal hormone therapy (MHT), likely due to factors related to the MHT used, ER profile, and RCT design. Some MHT forms, dose, combinations or route of administration may have inadequate vascular effects. Age-related changes in ER amount, distribution, integrity and post-ER signaling could alter the vascular response to MHT. The subject’s age, preexisting CVD, and hormone environment could also reduce the effects of MHT. Further evaluation of natural and synthetic estrogens, phytoestrogens, and selective estrogen-receptor modulators (SERMs), and the design of appropriate MHT combinations, dose, route and 'timing' could improve the effectiveness of conventional MHT and provide alternative therapies in the peri-menopausal period. Targeting ER using specific ER agonists, localized MHT delivery, and activation of specific post-ER signaling pathways could counter age-related changes in ER. Examination of the hormone environment and conditions associated with hormone imbalance such as polycystic ovary syndrome may reveal the causes of abnormal hormone-receptor interactions. Consideration of these factors in new RCTs such as the Kronos Early Estrogen Prevention Study (KEEPS) could enhance the vascular benefits of estrogen in postmenopausal CVD. PMID:24099797

  13. Society for Vascular Medicine

    MedlinePlus

    ... Sessions June 14-17, 2017 Sheraton New Orleans New Orleans, LA USA Board Review Course June 16-18, 2017 SVM in the Vascular Lab June 17, 2017 Learn more Patient Information Pages from Vascular Medicine October 2016 Smoking Cessation More info for patients. SVM Case ...

  14. [Vascular graft prosthesis].

    PubMed

    Chakfé, N; Dieval, F; Thaveau, F; Rinckenbach, S; Hassani, O; Camelot, G; Durand, B; Kretz, J-G

    2004-06-01

    Performed since the 1950s, vascular grafting has opened modern era of vascular surgery. Autologous venous grafts are of first choice for revascularisation of small arteries. Synthetic grafts are mainly modelled using microporous polytetrafluoroethylene or terephtalate polyethylene. These prosthesis are mainly used for revascularization of medium and large size arteries. PMID:15220107

  15. [Vascular factors in glaucoma].

    PubMed

    Mottet, B; Aptel, F; Geiser, M; Romanet, J P; Chiquet, C

    2015-12-01

    The exact pathophysiology of glaucoma is not fully understood. Understanding of the vascular pathophysiology of glaucoma requires: knowing the techniques for measuring ocular blood flow and characterizing the topography of vascular disease and the mechanisms involved in this neuropathy. A decreased mean ocular perfusion pressure and a loss of vascular autoregulation are implicated in glaucomatous disease. Early decrease in ocular blood flow has been identified in primary open-angle glaucoma and normal pressure glaucoma, contributing to the progression of optic neuropathy. The vascular damage associated with glaucoma is present in various vascular territories within the eye (from the ophthalmic artery to the retina) and is characterized by a decrease in basal blood flow associated with a dysfunction of vasoregulation.

  16. [Vascular factors in glaucoma].

    PubMed

    Mottet, B; Aptel, F; Geiser, M; Romanet, J P; Chiquet, C

    2015-12-01

    The exact pathophysiology of glaucoma is not fully understood. Understanding of the vascular pathophysiology of glaucoma requires: knowing the techniques for measuring ocular blood flow and characterizing the topography of vascular disease and the mechanisms involved in this neuropathy. A decreased mean ocular perfusion pressure and a loss of vascular autoregulation are implicated in glaucomatous disease. Early decrease in ocular blood flow has been identified in primary open-angle glaucoma and normal pressure glaucoma, contributing to the progression of optic neuropathy. The vascular damage associated with glaucoma is present in various vascular territories within the eye (from the ophthalmic artery to the retina) and is characterized by a decrease in basal blood flow associated with a dysfunction of vasoregulation. PMID:26597554

  17. Bioactive scaffolds for engineering vascularized cardiac tissues

    PubMed Central

    Chiu, Loraine; Radisic, Milica; Vunjak-Novakovic, Gordana

    2013-01-01

    Functional vascularization is a key requirement for the development and function of most tissues, and most critically cardiac muscle. Rapid and irreversible loss of cardiomyocytes during cardiac infarction directly results from the lack of blood supply. Contractile cardiac grafts, engineered using cardiovascular cells in conjunction with biomaterial scaffolds, are an actively studied method for cardiac repair. In this article, we focus on biomaterial scaffolds designed to mediate the development and maturation of vascular networks, by immobilized growth factors. The interactive effects of multiple vasculogenic factors are discussed in the context of cardiac tissue engineering. PMID:20857391

  18. Ictal Cardiac Ryhthym Abnormalities

    PubMed Central

    Ali, Rushna

    2016-01-01

    Cardiac rhythm abnormalities in the context of epilepsy are a well-known phenomenon. However, they are under-recognized and often missed. The pathophysiology of these events is unclear. Bradycardia and asystole are preceded by seizure onset suggesting ictal propagation into the cortex impacting cardiac autonomic function, and the insula and amygdala being possible culprits. Sudden unexpected death in epilepsy (SUDEP) refers to the unanticipated death of a patient with epilepsy not related to status epilepticus, trauma, drowning, or suicide. Frequent refractory generalized tonic-clonic seizures, anti-epileptic polytherapy, and prolonged duration of epilepsy are some of the commonly identified risk factors for SUDEP. However, the most consistent risk factor out of these is an increased frequency of generalized tonic–clonic seizures (GTC). Prevention of SUDEP is extremely important in patients with chronic, generalized epilepsy. Since increased frequency of GTCS is the most consistently reported risk factor for SUDEP, effective seizure control is the most important preventive strategy. PMID:27347227

  19. Ictal Cardiac Ryhthym Abnormalities.

    PubMed

    Ali, Rushna

    2016-01-01

    Cardiac rhythm abnormalities in the context of epilepsy are a well-known phenomenon. However, they are under-recognized and often missed. The pathophysiology of these events is unclear. Bradycardia and asystole are preceded by seizure onset suggesting ictal propagation into the cortex impacting cardiac autonomic function, and the insula and amygdala being possible culprits. Sudden unexpected death in epilepsy (SUDEP) refers to the unanticipated death of a patient with epilepsy not related to status epilepticus, trauma, drowning, or suicide. Frequent refractory generalized tonic-clonic seizures, anti-epileptic polytherapy, and prolonged duration of epilepsy are some of the commonly identified risk factors for SUDEP. However, the most consistent risk factor out of these is an increased frequency of generalized tonic-clonic seizures (GTC). Prevention of SUDEP is extremely important in patients with chronic, generalized epilepsy. Since increased frequency of GTCS is the most consistently reported risk factor for SUDEP, effective seizure control is the most important preventive strategy. PMID:27347227

  20. Communication and abnormal behaviour.

    PubMed

    Crown, S

    1979-01-01

    In this paper the similarities between normal and abnormal behaviour are emphasized and selected aspects of communication, normal and aberrant, between persons are explored. Communication in a social system may be verbal or non-verbal: one person's actions cause a response in another person. This response may be cognitive, behavioural or physiological. Communication may be approached through the individual, the social situation or social interaction. Psychoanalysis approaches the individual in terms of the coded communications of psychoneurotic symptoms or psychotic behaviour; the humanist-existential approach is concerned more with emotional expression. Both approaches emphasize the development of individual identity. The interaction between persons and their social background is stressed. Relevant are sociological concepts such as illness behaviour, stigma, labelling, institutionalization and compliance. Two approaches to social interactions are considered: the gamesplaying metaphor, e.g. back pain as a psychosocial manipulation--the 'pain game'; and the 'spiral of reciprocal perspectives' which emphasizes the interactional complexities of social perceptions. Communicatory aspects of psychological treatments are noted: learning a particular metaphor such as 'resolution' of the problem (psychotherapy), learning more 'rewarding' behaviour (learning theory) or learning authenticity or self-actualization (humanist-existential).

  1. Communication and abnormal behaviour.

    PubMed

    Crown, S

    1979-01-01

    In this paper the similarities between normal and abnormal behaviour are emphasized and selected aspects of communication, normal and aberrant, between persons are explored. Communication in a social system may be verbal or non-verbal: one person's actions cause a response in another person. This response may be cognitive, behavioural or physiological. Communication may be approached through the individual, the social situation or social interaction. Psychoanalysis approaches the individual in terms of the coded communications of psychoneurotic symptoms or psychotic behaviour; the humanist-existential approach is concerned more with emotional expression. Both approaches emphasize the development of individual identity. The interaction between persons and their social background is stressed. Relevant are sociological concepts such as illness behaviour, stigma, labelling, institutionalization and compliance. Two approaches to social interactions are considered: the gamesplaying metaphor, e.g. back pain as a psychosocial manipulation--the 'pain game'; and the 'spiral of reciprocal perspectives' which emphasizes the interactional complexities of social perceptions. Communicatory aspects of psychological treatments are noted: learning a particular metaphor such as 'resolution' of the problem (psychotherapy), learning more 'rewarding' behaviour (learning theory) or learning authenticity or self-actualization (humanist-existential). PMID:261653

  2. Abnormal uterine bleeding.

    PubMed

    Whitaker, Lucy; Critchley, Hilary O D

    2016-07-01

    Abnormal uterine bleeding (AUB) is a common and debilitating condition with high direct and indirect costs. AUB frequently co-exists with fibroids, but the relationship between the two remains incompletely understood and in many women the identification of fibroids may be incidental to a menstrual bleeding complaint. A structured approach for establishing the cause using the Fédération International de Gynécologie et d'Obstétrique (FIGO) PALM-COEIN (Polyp, Adenomyosis, Leiomyoma, Malignancy (and hyperplasia), Coagulopathy, Ovulatory disorders, Endometrial, Iatrogenic and Not otherwise classified) classification system will facilitate accurate diagnosis and inform treatment options. Office hysteroscopy and increasing sophisticated imaging will assist provision of robust evidence for the underlying cause. Increased availability of medical options has expanded the choice for women and many will no longer need to recourse to potentially complicated surgery. Treatment must remain individualised and encompass the impact of pressure symptoms, desire for retention of fertility and contraceptive needs, as well as address the management of AUB in order to achieve improved quality of life. PMID:26803558

  3. Abortion for fetal abnormality.

    PubMed

    Maclean, N E

    1979-07-25

    I wish to thank Dr. Pauline Bennett for her reply (NZ Med J, 13 June). She has demonstrated well that in dealing with sensitive difficult issues such as abortion for fetal abnormality, the one thing the doctor is not recommended to do is to speak the truth] I am prompted to write this letter for 2 reasons. Firstly, the excellent letter written by Dr. A. M. Rutherford (NZ Med J, 13 June) on the subject of abortion stated, "The most disturbing feature about the whole controversy is the 'blunting of our conscience'." When the doctors are not encouraged to be honest with patients then indeed our conscience has been blunted. Secondly, I watched Holocaust last night, and cannot refrain from stating that I see frightening parallels between our liberal abortion policy and the activities of the Nazis. As I watched the "mental patients" being herded into the shed for gassing by the polite, tidy, white coated medical staff, and then heard the compassionate, sensitive, letter of the hospital authorities to the relatives of the deceased, the parallel became obvious. The mental patients were weak, defenseless, burdensome, and uneconomic; the unborn are weak, defenseless, burdensome, and uneconomic. The hospital authority's letter was acceptable in many ways, acceptable except that its words bore no relation to the truth. It is said that the "first casualty of war is the truth". Whether that war involves the Jews, or the insane, or the unborn, the statement would seem correct.

  4. Nrf2/Keap1 system regulates vascular smooth muscle cell apoptosis for vascular homeostasis: role in neointimal formation after vascular injury

    PubMed Central

    Ashino, Takashi; Yamamoto, Masayuki; Numazawa, Satoshi

    2016-01-01

    Abnormal increases in vascular smooth muscle cells (VSMCs) in the intimal region after a vascular injury is a key event in developing neointimal hyperplasia. To maintain vascular function, proliferation and apoptosis of VSMCs is tightly controlled during vascular remodeling. NF-E2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) system, a key component of the oxidative stress response that acts in maintaining homeostasis, plays an important role in neointimal hyperplasia after a vascular injury; however, the role of Nrf2/Keap1 in VSMC apoptosis has not been clarified. Here we report that 14 days after arterial injury in mice, TUNEL-positive VSMCs are detected in both the neointimal and medial layers. These layers contain cells expressing high levels of Nrf2 but low Keap1 expression. In VSMCs, Keap1 depletion induces features of apoptosis, such as positive TUNEL staining and annexin V binding. These changes are associated with an increased expression of nuclear Nrf2. Simultaneous Nrf2 depletion inhibits Keap1 depletion-induced apoptosis. At 14 days after the vascular injury, Nrf2-deficient mice demonstrated fewer TUNEL-positive cells and increased neointimal formation in the neointimal and medial areas. The results suggest that the Nrf2/Keap1 system regulates VSMC apoptosis during neointimal formation, thereby inhibiting neointimal hyperplasia after a vascular injury. PMID:27198574

  5. Effects of lead on vascular reactivity.

    PubMed Central

    Chai, S S; Webb, R C

    1988-01-01

    Considerable controversy exists concerning the possible role of lead in the etiology of human hypertension. In animal studies, there is convincing evidence that lead alters cardiovascular responsiveness; rats drinking water containing 100 ppm lead develop a chronic, significant 15 to 20 mm Hg elevation in systolic blood pressure. Pressor responsiveness to catecholamines is enhanced in animals chronically exposed to lead, and the responsiveness of isolated vascular smooth muscle to adrenergic agonists is increased in rats with lead-induced hypertension. Experimental evidence suggests that alterations in the cellular mechanisms that regulate intracellular calcium concentration may contribute to the abnormal vascular function in lead-induced hypertension. Recent work in our laboratory indicates that increased vascular reactivity in genetic hypertension is associated with altered activity of the protein kinase C branch of the calcium messenger system. Contractile responses to lead in rabbit mesenteric artery are potentiated by activators (phorbol esters) of this enzyme complex, and a selective inhibitor of protein kinase C inhibited contractions induced by lead. Based on these results, it is proposed that a cellular component of the action of lead to increase vascular reactivity may relate to the role of protein kinase C in smooth muscle contraction. PMID:3060355

  6. Vascular nitric oxide: formation and function

    PubMed Central

    Jin, Richard C; Loscalzo, Joseph

    2010-01-01

    Nitric oxide (NO) is a structurally simple, highly versatile molecule that was originally discovered over 30 years ago as an endothelium-derived relaxing factor. In addition to its vasorelaxing effects, NO is now recognized as a key determinant of vascular health, exerting antiplatelet, antithrombotic, and anti-inflammatory properties within the vasculature. This short-lived molecule exerts its inhibitory effect on vascular smooth muscle cells and platelets largely through cyclic guanosine monophosphate-dependent mechanisms, resulting in a multitude of molecular effects by which platelet activation and aggregation are prevented. The biosynthesis of NO occurs via the catalytic activity of NO synthase, an oxidoreductase found in many cell types. NO insufficiency can be attributed to limited substrate/cofactor availability as well as interactions with reactive oxygen species. Impaired NO bioavailability represents the central feature of endothelial dysfunction, a common abnormality found in many vascular diseases. In this review, we present an overview of NO synthesis and biochemistry, discuss the mechanisms of action of NO in regulating platelet and endothelial function, and review the effects of vascular disease states on NO bioavailability. PMID:21572574

  7. Retinal vascular tree reconstruction with anatomical realism.

    PubMed

    Lin, Kai-Shun; Tsai, Chia-Ling; Tsai, Chih-Hsiangng; Sofka, Michal; Chen, Shih-Jen; Lin, Wei-Yang

    2012-12-01

    Motivated by the goals of automatically extracting vessel segments and constructing retinal vascular trees with anatomical realism, this paper presents and analyses an algorithm that combines vessel segmentation and grouping of the extracted vessel segments. The proposed method aims to restore the topology of the vascular trees with anatomical realism for clinical studies and diagnosis of retinal vascular diseases, which manifest abnormalities in either venous and/or arterial vascular systems. Vessel segments are grouped using extended Kalman filter which takes into account continuities in curvature, width, and intensity changes at the bifurcation or crossover point. At a junction, the proposed method applies the minimum-cost matching algorithm to resolve the conflict in grouping due to error in tracing. The system was trained with 20 images from the DRIVE dataset, and tested using the remaining 20 images. The dataset contained a mixture of normal and pathological images. In addition, six pathological fluorescein angiogram sequences were also included in this study. The results were compared against the groundtruth images provided by a physician, achieving average success rates of 88.79% and 90.09%, respectively.

  8. Vascular Access in Children

    SciTech Connect

    Krishnamurthy, Ganesh Keller, Marc S.

    2011-02-15

    Establishment of stable vascular access is one of the essential and most challenging procedures in a pediatric hospital. Many clinical specialties provide vascular service in a pediatric hospital. At the top of the 'expert procedural pyramid' is the pediatric interventional radiologist, who is best suited and trained to deliver this service. Growing awareness regarding the safety and high success rate of vascular access using image guidance has led to increased demand from clinicians to provide around-the-clock vascular access service by pediatric interventional radiologists. Hence, the success of a vascular access program, with the pediatric interventional radiologist as the key provider, is challenging, and a coordinated multidisciplinary team effort is essential for success. However, there are few dedicated pediatric interventional radiologists across the globe, and also only a couple of training programs exist for pediatric interventions. This article gives an overview of the technical aspects of pediatric vascular access and provides useful tips for obtaining vascular access in children safely and successfully using image guidance.

  9. Networks.

    ERIC Educational Resources Information Center

    Cerf, Vinton G.

    1991-01-01

    The demands placed on the networks transporting the information and knowledge generated by the increased diversity and sophistication of computational machinery are described. What is needed to support this increased flow, the structures already in place, and what must be built are topics of discussion. (KR)

  10. CSF biomarkers in neurodegenerative and vascular dementias.

    PubMed

    Llorens, Franc; Schmitz, Matthias; Ferrer, Isidro; Zerr, Inga

    2016-01-01

    Neurodegenerative diseases with abnormal protein aggregates such as Alzheimer's disease, tauopathies, synucleinopathies, and prionopathies, together with vascular encephalopathies, are cause of cognitive impairment and dementia. Identification of reliable biomarkers in biological fluids, particularly in the cerebrospinal fluid (CSF), is of extreme importance in optimizing the precise early clinical diagnosis of distinct entities and predicting the outcome in particular settings. In addition, the study of CSF biomarkers is useful to identify and monitor the underlying pathological processes developing in the central nervous system of affected individuals. Evidence suggests that levels of key CSF molecules correlate, in some circumstances, with prediction, disease progression, and severity of cognitive decline. Correlation of CSF markers and underlying pathological molecular substrates in brain is an exciting field for further study. However, while some dementias such as Creutzfeldt-Jakob disease have accurate CSF biomarkers, other disease types such as dementia with Lewy bodies, vascular dementia, and frontotemporal dementia lack reliable biomarkers for their specific clinical diagnosis. PMID:27016008

  11. Disrupted pulmonary vascular development and pulmonary hypertension in transgenic mice overexpressing transforming growth factor-alpha.

    PubMed

    Le Cras, Timothy D; Hardie, William D; Fagan, Karen; Whitsett, Jeffrey A; Korfhagen, Thomas R

    2003-11-01

    Pulmonary vascular disease plays a major role in morbidity and mortality in infant and adult lung diseases in which increased levels of transforming growth factor (TGF)-alpha and its receptor EGFR have been associated. The aim of this study was to determine whether overexpression of TGF-alpha disrupts pulmonary vascular development and causes pulmonary hypertension. Lung-specific expression of TGF-alpha in transgenic mice was driven with the human surfactant protein (SP)-C promoter. Pulmonary arteriograms and arterial counts show that pulmonary vascular development was severely disrupted in TGF-alpha mice. TGF-alpha mice developed severe pulmonary hypertension and vascular remodeling characterized by abnormally extensive muscularization of small pulmonary arteries. Pulmonary vascular development was significantly improved and pulmonary hypertension and vascular remodeling were prevented in bi-transgenic mice expressing both TGF-alpha and a dominant-negative mutant EGF receptor under the control of the SP-C promoter. Vascular endothelial growth factor (VEGF-A), an important angiogenic factor produced by the distal epithelium, was decreased in the lungs of TGF-alpha adults and in the lungs of infant TGF-alpha mice before detectable abnormalities in pulmonary vascular development. Hence, overexpression of TGF-alpha caused severe pulmonary vascular disease, which was mediated through EGFR signaling in distal epithelial cells. Reductions in VEGF may contribute to the pathogenesis of pulmonary vascular disease in TGF-alpha mice.

  12. Microvascular Repair: Post-Angiogenesis Vascular Dynamics

    PubMed Central

    LeBlanc, Amanda J.; Krishnan, Laxminarayanan; Sullivan, Christopher J.; Williams, Stuart K.; Hoying, James B.

    2013-01-01

    Vascular compromise and the accompanying perfusion deficits cause or complicate a large array of disease conditions and treatment failures. This has prompted the exploration of therapeutic strategies to repair or regenerate vasculatures thereby establishing more competent microcirculatory beds. Growing evidence indicates that an increase in vessel numbers within a tissue does not necessarily promote an increase in tissue perfusion. Effective regeneration of a microcirculation entails the integration of new stable microvessel segments into the network via neovascularization. Beginning with angiogenesis, neovascularization entails an integrated series of vascular activities leading to the formation of a new mature microcirculation and includes vascular guidance and inosculation, vessel maturation, pruning, arterio-venous specification, network patterning, structural adaptation, intussusception, and microvascular stabilization. While the generation of new vessel segments is necessary to expand a network, without the concomitant neovessel remodeling and adaptation processes intrinsic to microvascular network formation, these additional vessel segments give rise to a dysfunctional microcirculation. While many of the mechanisms regulating angiogenesis have been detailed, a thorough understanding of the mechanisms driving post-angiogenesis activities specific to neovascularization has yet to be fully realized, but is necessary in order to develop effective therapeutic strategies for repairing compromised microcirculations as a means to treat disease. PMID:22734666

  13. Haem degradation in abnormal haemoglobins.

    PubMed Central

    Brown, S B; Docherty, J C

    1978-01-01

    The coupled oxidation of certain abnormal haemoglobins leads to different bile-pigment isomer distributions from that of normal haemoglobin. The isomer pattern may be correlated with the structure of the abnormal haemoglobin in the neighbourhood of the haem pocket. This is support for haem degradation by an intramolecular reaction. PMID:708385

  14. Systemic abnormalities in liver disease

    PubMed Central

    Minemura, Masami; Tajiri, Kazuto; Shimizu, Yukihiro

    2009-01-01

    Systemic abnormalities often occur in patients with liver disease. In particular, cardiopulmonary or renal diseases accompanied by advanced liver disease can be serious and may determine the quality of life and prognosis of patients. Therefore, both hepatologists and non-hepatologists should pay attention to such abnormalities in the management of patients with liver diseases. PMID:19554648

  15. Abnormal pressure in hydrocarbon environments

    USGS Publications Warehouse

    Law, B.E.; Spencer, C.W.

    1998-01-01

    Abnormal pressures, pressures above or below hydrostatic pressures, occur on all continents in a wide range of geological conditions. According to a survey of published literature on abnormal pressures, compaction disequilibrium and hydrocarbon generation are the two most commonly cited causes of abnormally high pressure in petroleum provinces. In young (Tertiary) deltaic sequences, compaction disequilibrium is the dominant cause of abnormal pressure. In older (pre-Tertiary) lithified rocks, hydrocarbon generation, aquathermal expansion, and tectonics are most often cited as the causes of abnormal pressure. The association of abnormal pressures with hydrocarbon accumulations is statistically significant. Within abnormally pressured reservoirs, empirical evidence indicates that the bulk of economically recoverable oil and gas occurs in reservoirs with pressure gradients less than 0.75 psi/ft (17.4 kPa/m) and there is very little production potential from reservoirs that exceed 0.85 psi/ft (19.6 kPa/m). Abnormally pressured rocks are also commonly associated with unconventional gas accumulations where the pressuring phase is gas of either a thermal or microbial origin. In underpressured, thermally mature rocks, the affected reservoirs have most often experienced a significant cooling history and probably evolved from an originally overpressured system.

  16. Electrocardiograph abnormalities revealed during laparoscopy.

    PubMed

    Nijjer, Sukhjinder; Dubrey, Simon William

    2010-01-01

    This brief case presents a well patient in whom an electrocardiograph abnormality consistent with an accessory pathway was found during a routine procedure. We present the electrocardiographs, explain the underlying condition, and consider why the abnormality was revealed in this manner.

  17. [Vascular factors in dementia].

    PubMed

    Bidzan, Leszek

    2005-01-01

    Cerebrovascular factors are a common cause of dementia or contribute to cognitive decline in other dementias. Studies showing that cerebrovascular factors are the risk factors for neurodegenerative dementias, especially Alzheimer's disease. Practically all neurodegenerative dementias have a vascular component that reduces cerebral perfusion and has great impact on the clinical picture. Recent data support the view that the neurodegenerative process is caused by cerebrovascular mechanisms. The results showed that patients with vascular cognitive impairment have a typical clinical picture. Various important non-cognitive features are caused by cerebrovascular factors and are associated with a more rapid course of illness. On the other hand the term vascular diseases or cerebrovascular factors include a variety of vascular pathologies. PMID:16358596

  18. Heart and vascular services

    MedlinePlus

    ... scan of the heart Stress tests (many different types of stress tests exist) Vascular ultrasound, such as carotid ultrasound Venous ultrasound of the arms and legs SURGERIES AND INTERVENTIONS ... these types of procedures, a catheter is inserted through the ...

  19. Vascular Disease Foundation

    MedlinePlus

    ... or 911 immediately. @ 2016 Vascular Cures is a tax-exempt, nonprofit organization tax ID#: 94-2825216 as described in the Section ... 3) of the Internal Revenue Code. Donations are tax deductible. 555 Price Ave., Suite 180, Redwood City, ...

  20. Implications of Vascular Aging

    PubMed Central

    Barodka, Viachaslau M.; Joshi, Brijen L.; Berkowitz, Dan E.; Hogue, Charles W.; Nyhan, Daniel

    2011-01-01

    Chronological age is a well established risk factor for the development of cardiovascular diseases. The changes that accumulate in the vasculature with age, though, are highly variable. It is now increasingly recognized that indices of vascular health are more reliable than age per se in predicting adverse cardiovascular outcomes. The variation in the accrual of these age-related vascular changes is a function of multiple genetic and environmental factors. In this review, we highlight some of the pathophysiological mechanisms that characterize the vascular aging phenotype. Furthermore, we provide an overview of the key outcome studies that address the value of these vascular health indices in general and discuss potential effects on perioperative cardiovascular outcomes. PMID:21474663

  1. Sinuosities in vascular structures

    NASA Astrophysics Data System (ADS)

    Masson, J.-B.; Martin, J.-L.

    2007-12-01

    In most organs, depending on the scale, the nature of the heart pump, the geometry and topology of the organ, some of the blood vessels tend to exhibit sinuous trajectories. We describe a part of this sinuous behavior, including partial biological and strong physical effects in a global physical framework. We will voluntarily focus on physical and topological effects. This study is performed on the vitelline membrane of the chicken embryo. Crossing angles, sinuosity, and the oscillation amplitude of the vascular system are analyzed. Surprisingly, the equation of river meandering dynamics is found to model the sinuosities in the vascular system, and an extension of this equation to non planar case is able to explain the effect of tissue global curvature on the vascular system. Results of this study could lead to a new understanding of the interplay between biological signaling and physical effects in determining the vascular pattern in different tissues.

  2. What Is Vascular Disease?

    MedlinePlus

    ... or 911 immediately. @ 2016 Vascular Cures is a tax-exempt, nonprofit organization tax ID#: 94-2825216 as described in the Section ... 3) of the Internal Revenue Code. Donations are tax deductible. 555 Price Ave., Suite 180, Redwood City, ...

  3. Women and Vascular Disease

    MedlinePlus

    ... Search Patient information Membership Directory (SIR login) Interventional Radiology Women and Vascular Disease Early Warning Symptom for ... major public health issue, the Society of Interventional Radiology recommends greater screening efforts by the medical community ...

  4. Vascular structures in dermoscopy*

    PubMed Central

    Ayhan, Erhan; Ucmak, Derya; Akkurt, ZeynepMeltem

    2015-01-01

    Dermoscopy is an aiding method in the visualization of the epidermis and dermis. It is usually used to diagnose melanocytic lesions. In recent years, dermoscopy has increasingly been used to diagnose non-melanocytic lesions. Certain vascular structures, their patterns of arrangement and additional criteria may demonstrate lesion-specific characteristics. In this review, vascular structures and their arrangements are discussed separately in the light of conflicting views and an overview of recent literature. PMID:26375224

  5. Vascular Hyperpermeability and Aging

    PubMed Central

    Oakley, Ryan; Tharakan, Binu

    2014-01-01

    Vascular hyperpermeability, the excessive leakage of fluid and proteins from blood vessels to the interstitial space, commonly occurs in traumatic and ischemic injuries. This hyperpermeability causes tissue vasogenic edema, which often leads to multiple organ failure resulting in patient death. Vascular hyperpermeability occurs most readily in small blood vessels as their more delicate physical constitution makes them an easy target for barrier dysfunction. A single layer of endothelial cells, linked to one another by cell adhesion molecules, covers the interior surface of each blood vessel. The cell adhesion molecules play a key role in maintaining barrier functions like the regulation of permeability. Aging is a major risk factor for microvascular dysfunction and hyperpermeability. Apart from age-related remodeling of the vascular wall, endothelial barrier integrity and function declines with the advancement of age. Studies that address the physiological and molecular basis of vascular permeability regulation in aging are currently very limited. There have been many cellular and molecular mechanisms proposed to explain aging-related endothelial dysfunction but their true relationship to barrier dysfunction and hyperpermeability is not clearly known. Among the several mechanisms that promote vascular dysfunction and hyperpermeability, the following are considered major contributors: oxidative stress, inflammation, and the activation of apoptotic signaling pathways. In this review we highlighted (a) the physiological, cellular and molecular changes that occur in the vascular system as a product of aging; (b) the potential mechanisms by which aging leads to barrier dysfunction and vascular hyperpermeability in the peripheral and the blood-brain barrier; (c) the mechanisms by which the age-related increases in oxidative stress, inflammatory markers and apoptotic signaling etc. cause endothelial dysfunction and their relationship to hyperpermeability; and (d) the

  6. Assessing vascular dementia.

    PubMed

    Forette, F; Rigaud, A S; Morin, M; Gisselbrecht, M; Bert, P

    1995-10-01

    Vascular dementia is the most common cause of dementia in the elderly after Alzheimer's disease. Many forms of vascular dementia have been described: multi-infarct dementia, lacunar dementia, Binswanger's subcortical encephalopathy, cerebral amyloid angiopathy, white matter lesions associated with dementias, single infarct dementia, dementia linked to hypoperfusion and haemorrhagic dementia. The difficulty of diagnosing vascular dementia must not be underestimated and an international consensus is needed for epidemiological studies. The NINCDS-AIREN group has recently published diagnostic criteria. The State of California Alzheimer's Disease Diagnostic and Treatment Centers also proposed some which differ from the NINCDS-AIREN criteria in considering only ischaemic vascular dementia and not other mechanisms such as haemorrhagic or hypoxic lesions. Most studies stress hypertension as the most powerful risk factor for all forms of vascular dementia. The incidence rate ranges from 7 per 1000 person-years in normal volunteers to 16 per 1000 person-years in hypertensive patients. No therapeutic attempt has influenced the course of the disease once the dementing condition is established. The only effective approach is preventive treatment. The objective of the SYST-EUR Vascular Dementia project is to confirm that the treatment of isolated systolic hypertension is able to reduce its incidence.

  7. Vascular Permeability and Drug Delivery in Cancers

    PubMed Central

    Azzi, Sandy; Hebda, Jagoda K.; Gavard, Julie

    2013-01-01

    The endothelial barrier strictly maintains vascular and tissue homeostasis, and therefore modulates many physiological processes such as angiogenesis, immune responses, and dynamic exchanges throughout organs. Consequently, alteration of this finely tuned function may have devastating consequences for the organism. This is particularly obvious in cancers, where a disorganized and leaky blood vessel network irrigates solid tumors. In this context, vascular permeability drives tumor-induced angiogenesis, blood flow disturbances, inflammatory cell infiltration, and tumor cell extravasation. This can directly restrain the efficacy of conventional therapies by limiting intravenous drug delivery. Indeed, for more effective anti-angiogenic therapies, it is now accepted that not only should excessive angiogenesis be alleviated, but also that the tumor vasculature needs to be normalized. Recovery of normal state vasculature requires diminishing hyperpermeability, increasing pericyte coverage, and restoring the basement membrane, to subsequently reduce hypoxia, and interstitial fluid pressure. In this review, we will introduce how vascular permeability accompanies tumor progression and, as a collateral damage, impacts on efficient drug delivery. The molecular mechanisms involved in tumor-driven vascular permeability will next be detailed, with a particular focus on the main factors produced by tumor cells, especially the emblematic vascular endothelial growth factor. Finally, new perspectives in cancer therapy will be presented, centered on the use of anti-permeability factors and normalization agents. PMID:23967403

  8. [The effects of DNA methylation on the homeostasis in vascular diseases].

    PubMed

    Xiaoying, Chen; Huadan, Ye; Qingxiao, Hong; Annan, Zhou; Linlin, Tang; Shiwei, Duan

    2015-03-01

    Homeostasis is fundamental to maintain normal physiological functions in our body. Internal and external physical, chemical and biologial changes can cause dysregulation of vascular homeostasis, which is closely associated with the homeostasis of oxygen supply, blood transportation and lipid metabolism. Subsequent epigenetic modifications are able to lead to abnormal structures and function of vessels. DNA methylation has been shown to play a vital role in the development of vascular diseases. In addition, 5-hydroxymethylcytosine (5hmC) and N(6)-methyladenine (m(6)A), as new epigenetic modifications, provide additional clues for vascular diseases. In this review, we summarize the effects of DNA methylation on the homeostasis dysregulation in the vascular diseases.

  9. Chromosomal abnormalities in human sperm

    SciTech Connect

    Martin, R.H.

    1985-01-01

    The ability to analyze human sperm chromosome complements after penetration of zona pellucida-free hamster eggs provides the first opportunity to study the frequency and type of chromosomal abnormalities in human gametes. Two large-scale studies have provided information on normal men. We have studied 1,426 sperm complements from 45 normal men and found an abnormality rate of 8.9%. Brandriff et al. (5) found 8.1% abnormal complements in 909 sperm from 4 men. The distribution of numerical and structural abnormalities was markedly dissimilar in the 2 studies. The frequency of aneuploidy was 5% in our sample and only 1.6% in Brandriff's, perhaps reflecting individual variability among donors. The frequency of 24,YY sperm was low: 0/1,426 and 1/909. This suggests that the estimates of nondisjunction based on fluorescent Y body data (1% to 5%) are not accurate. We have also studied men at increased risk of sperm chromosomal abnormalities. The frequency of chromosomally unbalanced sperm in 6 men heterozygous for structural abnormalities varied dramatically: 77% for t11;22, 32% for t6;14, 19% for t5;18, 13% for t14;21, and 0% for inv 3 and 7. We have also studied 13 cancer patients before and after radiotherapy and demonstrated a significant dose-dependent increase of sperm chromosome abnormalities (numerical and structural) 36 months after radiation treatment.

  10. Antioxidants and vascular health.

    PubMed

    Bielli, Alessandra; Scioli, Maria Giovanna; Mazzaglia, Donatella; Doldo, Elena; Orlandi, Augusto

    2015-12-15

    Oxygen free radicals and other reactive oxygen species (ROS) are common products of normal aerobic cellular metabolism, but high levels of ROS lead to oxidative stress and cellular damage. Increased production of ROS favors vascular dysfunction, inducing altered vascular permeability and inflammation, accompanied by the loss of vascular modulatory function, the imbalance between vasorelaxation and vasoconstriction, and the aberrant expression of inflammatory adhesion molecules. Inflammatory stimuli promote oxidative stress generated from the increased activity of mitochondrial nicotinamide adenine dinucleotide phosphate oxidase, particularly of the Nox4 isoform, with the consequent impairment of mitochondrial β-oxidation. Vascular dysfunction due to the increase in Nox4 activity and ROS overproduction leads to the progression of cardiovascular diseases, diabetes, inflammatory bowel disease, and neurological disorders. Considerable research into the development of effective antioxidant therapies using natural derivatives or new synthetic molecules has been conducted. Antioxidants may prevent cellular damage by reducing ROS overproduction or interfering in reactions that involve ROS. Vitamin E and ascorbic acid are well known as natural antioxidants that counteract lipid peroxidative damage by scavenging oxygen-derived free radicals, thus restoring vascular function. Recently, preliminary studies on natural antioxidants such as goji berries, thymus, rosemary, green tea ginseng, and garlic have been conducted for their efficacy in preventing vascular damage. N-acetyl-cysteine and propionyl-L-carnitine are synthetic compounds that regulate ROS production by replacing endogenous antioxidants in both endothelial and smooth muscle cells. In this review, we consider the molecular mechanisms underlying the generation of oxidative stress-induced vascular dysfunction as well as the beneficial effects of antioxidant therapies.

  11. Pressurized vascular systems for self-healing materials

    PubMed Central

    Hamilton, A. R.; Sottos, N. R.; White, S. R.

    2012-01-01

    An emerging strategy for creating self-healing materials relies on embedded vascular networks of microchannels to transport reactive fluids to regions of damage. Here we investigate the use of active pumping for the pressurized delivery of a two-part healing system, allowing a small vascular system to deliver large volumes of healing agent. Different pumping strategies are explored to improve the mixing and subsequent polymerization of healing agents in the damage zone. Significant improvements in the number of healing cycles and in the overall healing efficiency are achieved compared with prior passive schemes that use only capillary forces for the delivery of healing agents. At the same time, the volume of the vascular system required to achieve this superior healing performance is significantly reduced. In the best case, nearly full recovery of fracture toughness is attained throughout 15 cycles of damage and healing, with a vascular network constituting just 0.1 vol% of the specimen. PMID:21957119

  12. Arterial abnormalities of the shoulder in athletes.

    PubMed

    Nuber, G W; McCarthy, W J; Yao, J S; Schafer, M F; Suker, J R

    1990-01-01

    Vascular lesions of the shoulder may be misinterpreted as one of the more familiar shoulder abnormalities by a treating physician. We are reporting on 13 athletes who were found to have symptoms related to compression of the subclavian or axillary artery or their tributaries. Nine were amateur or professional baseball pitchers. Severe arm fatigue or finger ischemia, secondary to embolization, were presenting symptoms. Arm fatigue was noted in all pitchers. After complete history and physical examination, including auscultation for bruits in functional positions, all athletes were evaluated by noninvasive tests (Doppler and Duplex scanning). Arteriography was performed with positional testing, recreating overhead activity, and complete radiographic visualization of the dye to the digital arteries. Two patients were found to have subclavian artery aneurysm. The remaining athletes were found to have compression of the subclavian artery beneath the anterior scalene muscle (five patients), the axillary artery beneath the pectoralis minor (two patients), both arterial segments (two patients), and one was found to have arterial compromise at the level of the humeral head. Branch artery compression was also noted. One pitcher occluded the posterior circumflex humeral artery with embolization to the digit. The two patients with subclavian aneurysms underwent saphenous vein bypass with cervical rib resection. All of the other athletes except one underwent resection of a 2 to 3 cm segment of the anterior scalene muscle or pectoralis minor muscles. All returned to their previous level of activity except one patient who developed impingement type symptoms and required acromioplasty. He is currently undergoing rehabilitation. Proper recognition of vascular compromise in the upper extremity of athletes is essential to avoid the catastropic complications of arterial thrombosis.

  13. Vascular Anomalies: From Genetics toward Models for Therapeutic Trials

    PubMed Central

    Uebelhoer, Melanie; Boon, Laurence M.; Vikkula, Miikka

    2012-01-01

    Vascular anomalies are localized abnormalities that occur during vascular development. Several causative genes have been identified not only for inherited but also for some sporadic forms, and the molecular pathways involved are becoming understood. This gives us the opportunity to generate animals carrying the causative genetic defects, which we hope model the phenotype seen in human patients. These models would enable us not only to test known antiangiogenic drugs, but also to develop novel approaches for treatment, directly targeting the mutated protein or molecules implicated in the pathophysiological signaling pathways. PMID:22908197

  14. Towards organ printing: engineering an intra-organ branched vascular tree

    PubMed Central

    Visconti, Richard P; Kasyanov, Vladimir; Gentile, Carmine; Zhang, Jing; Markwald, Roger R; Mironov, Vladimir

    2013-01-01

    Importance of the field Effective vascularization of thick three-dimensional engineered tissue constructs is a problem in tissue engineering. As in native organs, a tissue-engineered intra-organ vascular tree must be comprised of a network of hierarchically branched vascular segments. Despite this requirement, current tissue-engineering efforts are still focused predominantly on engineering either large-diameter macrovessels or microvascular networks. Areas covered in this review We present the emerging concept of organ printing or robotic additive biofabrication of an intra-organ branched vascular tree, based on the ability of vascular tissue spheroids to undergo self-assembly. What the reader will gain The feasibility and challenges of this robotic biofabrication approach to intra-organ vascularization for tissue engineering based on organ-printing technology using self-assembling vascular tissue spheroids including clinically relevantly vascular cell sources are analyzed. Take home message It is not possible to engineer 3D thick tissue or organ constructs without effective vascularization. An effective intra-organ vascular system cannot be built by the simple connection of large-diameter vessels and microvessels. Successful engineering of functional human organs suitable for surgical implantation will require concomitant engineering of a ‘built in’ intra-organ branched vascular system. Organ printing enables biofabrication of human organ constructs with a ‘built in’ intra-organ branched vascular tree. PMID:20132061

  15. Microfluidics based phantoms of superficial vascular network

    PubMed Central

    Luu, Long; Roman, Patrick A.; Mathews, Scott A.; Ramella-Roman, Jessica C.

    2012-01-01

    Several new bio-photonic techniques aim to measure flow in the human vasculature non-destructively. Some of these tools, such as laser speckle imaging or Doppler optical coherence tomography, are now reaching the clinical stage. Therefore appropriate calibration and validation techniques dedicated to these particular measurements are therefore of paramount importance. In this paper we introduce a fast prototyping technique based on laser micromachining for the fabrication of dynamic flow phantoms. Micro-channels smaller than 20 µm in width can be formed in a variety of materials such as epoxies, plastics, and household tape. Vasculature geometries can be easily and quickly modified to accommodate a particular experimental scenario. PMID:22741081

  16. Coupling and robustness of intra-cortical vascular territories.

    PubMed

    Guibert, Romain; Fonta, Caroline; Risser, Laurent; Plouraboué, Franck

    2012-08-01

    Vascular domains have been described as being coupled to neuronal functional units enabling dynamic blood supply to the cerebral cyto-architecture. Recent experiments have shown that penetrating arterioles of the grey matter are the building blocks for such units. Nevertheless, vascular territories are still poorly known, as the collection and analysis of large three-dimensional micro-vascular networks are difficult. By using an exhaustive reconstruction of the micro-vascular network in an 18 mm(3) volume of marmoset cerebral cortex, we numerically computed the blood flow in each blood vessel. We thus defined arterial and venular territories and examined their overlap. A large part of the intracortical vascular network was found to be supplied by several arteries and drained by several venules. We quantified this multiple potential to compensate for deficiencies by introducing a new robustness parameter. Robustness proved to be positively correlated with cortical depth and a systematic investigation of coupling maps indicated local patterns of overlap between neighbouring arteries and neighbouring venules. However, arterio-venular coupling did not have a spatial pattern of overlap but showed locally preferential functional coupling, especially of one artery with two venules, supporting the notion of vascular units. We concluded that intra-cortical perfusion in the primate was characterised by both very narrow functional beds and a large capacity for compensatory redistribution, far beyond the nearest neighbour collaterals. PMID:22548806

  17. Pancreatic transplantation: Radiologic evaluation of vascular complications

    SciTech Connect

    Snider, J.F.; Hunter, D.W.; Kuni, C.C.; Castaneda-Zuniga, W.R.; Letourneau, J.G. )

    1991-03-01

    Transplantation of the pancreas is an increasingly common therapeutic option for preventing or delaying complications of type I diabetes mellitus. The authors studied the relative roles of various radiologic examinations in diagnosing vascular complications in these grafts including arterial and venous thrombosis, stenosis, and anastomotic leak (the most common vascular factors that necessitate pancreatectomy of the transplant), as defined with pathologic or arteriographic data. The results of 78 scintigraphic flow studies, 40 abdominal and pelvic computed tomographic (CT) scans, 27 sonograms, and eight color Doppler studies were evaluated in 52 patients who received a total of 27 cadaveric and 26 living-donor grafts over a 12-year period. These results were correlated with the data from 45 gross and microscopic pathologic studies and 37 arteriograms to determine their relative value in enabling detection of graft thrombosis and other vascular complications. Scintigraphy, CT, sonography, and color Doppler were all sensitive in detection of generalized graft abnormalities but lacked specificity in defining the underlying etiologic factors.

  18. Vascular parkinsonism--characteristics, pathogenesis and treatment.

    PubMed

    Korczyn, Amos D

    2015-06-01

    Parkinson disease is a primary degenerative disease of the brain, but parkinsonism can also result from a variety of vascular disorders. Vascular parkinsonism (VP) most frequently presents as lower body parkinsonism, a condition that is accompanied by the development of white matter lesions (WMLs) and lacunes in the brain. Patients with lower body parkinsonism exhibit gait impairment and go on to develop urinary incontinence, abnormal pyramidal responses and cognitive decline. However, WMLs and lacunes are also common observations among elderly individuals who do not have parkinsonism, which causes difficulty in determining the pathogenetic mechanisms that lead to VP. In addition, imaging studies suggest that many pathological and clinical features are common to VP and Binswanger disease, a type of small vessel vascular dementia. This Review summarizes current understanding of the clinical characteristics of VP, as well as knowledge gained from neuroimaging and nuclear imaging of the pathological features of VP. The lack of current treatment options, and the emergence of new therapies such as cerebrospinal fluid drainage, are also discussed. Finally, consideration is given to whether the overlap between VP and Binswanger disease means that these two disorders should be considered as part of the same disease entity. PMID:25917706

  19. Kidney transplantation in abnormal bladder

    PubMed Central

    Mishra, Shashi K.; Muthu, V.; Rajapurkar, Mohan M.; Desai, Mahesh R.

    2007-01-01

    Structural urologic abnormalities resulting in dysfunctional lower urinary tract leading to end stage renal disease may constitute 15% patients in the adult population and up to 20-30% in the pediatric population. A patient with an abnormal bladder, who is approaching end stage renal disease, needs careful evaluation of the lower urinary tract to plan the most satisfactory technical approach to the transplant procedure. Past experience of different authors can give an insight into the management and outcome of these patients. This review revisits the current literature available on transplantation in abnormal bladder and summarizes the clinical approach towards handling this group of difficult transplant patients. We add on our experience as we discuss the various issues. The outcome of renal transplant in abnormal bladder is not adversely affected when done in a reconstructed bladder. Correct preoperative evaluation, certain technical modification during transplant and postoperative care is mandatory to avoid complications. Knowledge of the abnormal bladder should allow successful transplantation with good outcome. PMID:19718334

  20. Vascular wall extracellular matrix proteins and vascular diseases

    PubMed Central

    Xu, Junyan; Shi, Guo-Ping

    2014-01-01

    Extracellular matrix proteins form the basic structure of blood vessels. Along with providing basic structural support to blood vessels, matrix proteins interact with different sets of vascular cells via cell surface integrin or non-integrin receptors. Such interactions induce vascular cell de novo synthesis of new matrix proteins during blood vessel development or remodeling. Under pathological conditions, vascular matrix proteins undergo proteolytic processing, yielding bioactive fragments to influence vascular wall matrix remodeling. Vascular cells also produce alternatively spliced variants that induce vascular cell production of different matrix proteins to interrupt matrix homeostasis, leading to increased blood vessel stiffness; vascular cell migration, proliferation, or death; or vascular wall leakage and rupture. Destruction of vascular matrix proteins leads to vascular cell or blood-borne leukocyte accumulation, proliferation, and neointima formation within the vascular wall; blood vessels prone to uncontrolled enlargement during blood flow diastole; tortuous vein development; and neovascularization from existing pathological tissue microvessels. Here we summarize discoveries related to blood vessel matrix proteins within the past decade from basic and clinical studies in humans and animals — from expression to cross-linking, assembly, and degradation under physiological and vascular pathological conditions, including atherosclerosis, aortic aneurysms, varicose veins, and hypertension. PMID:25045854

  1. Vascular air embolism

    PubMed Central

    Gordy, Stephanie; Rowell, Susan

    2013-01-01

    Vascular air embolism is a rare but potentially fatal event. It may occur in a variety of procedures and surgeries but is most often associated as an iatrogenic complication of central line catheter insertion. This article reviews the incidence, pathophysiology, diagnosis, treatment, and prevention of this phenomenon. PMID:23724390

  2. Adhesion in vascular biology

    PubMed Central

    de Rooij, Johan

    2014-01-01

    The vasculature delivers vital support for all other tissues by supplying oxygen and nutrients for growth and by transporting the immune cells that protect and cure them. Therefore, the microvasculature developed a special barrier that is permissive for gasses like oxygen and carbon dioxide, while fluids are kept inside and pathogens are kept out. While maintaining this tight barrier, the vascular wall also allows immune cells to exit at sites of inflammation or damage, a process that is called transmigration. The endothelial cell layer that forms the inner lining of the vasculature is crucial for the vascular barrier function as well as the regulation of transmigration. Therefore, adhesions between vascular endothelial cells are both tight and dynamic and the mechanisms by which they are established, and the mechanisms by which they are controlled have been extensively studied over the past decades. Because of our fundamental strive to understand biology, but also because defects in vascular barrier control cause a variety of clinical problems and treatment strategies may evolve from our detailed understanding of its mechanisms. This special focus issue features a collection of articles that review key components of the development and control of the endothelial cell-cell junction that is central to endothelial barrier function. PMID:25422845

  3. Engineered Vascularized Muscle Flap.

    PubMed

    Egozi, Dana; Shandalov, Yulia; Freiman, Alina; Rosenfeld, Dekel; Ben-Shimol, David; Levenberg, Shulamit

    2016-01-01

    One of the main factors limiting the thickness of a tissue construct and its consequential viability and applicability in vivo, is the control of oxygen supply to the cell microenvironment, as passive diffusion is limited to a very thin layer. Although various materials have been described to restore the integrity of full-thickness defects of the abdominal wall, no material has yet proved to be optimal, due to low graft vascularization, tissue rejection, infection, or inadequate mechanical properties. This protocol describes a means of engineering a fully vascularized flap, with a thickness relevant for muscle tissue reconstruction. Cell-embedded poly L-lactic acid/poly lactic-co-glycolic acid constructs are implanted around the mouse femoral artery and vein and maintained in vivo for a period of one or two weeks. The vascularized graft is then transferred as a flap towards a full thickness defect made in the abdomen. This technique replaces the need for autologous tissue sacrifications and may enable the use of in vitro engineered vascularized flaps in many surgical applications. PMID:26779840

  4. Identification of Vascular Lineage-Specific Genes by Transcriptional Profiling of Isolated Blood Vascular and Lymphatic Endothelial Cells

    PubMed Central

    Hirakawa, Satoshi; Hong, Young-Kwon; Harvey, Natasha; Schacht, Vivien; Matsuda, Kant; Libermann, Towia; Detmar, Michael

    2003-01-01

    In mammals, the lymphatic vascular system develops by budding of lymphatic progenitor endothelial cells from embryonic veins to form a distinct network of draining vessels with important functions in the immune response and in cancer metastasis. However, the lineage-specific molecular characteristics of blood vascular versus lymphatic endothelium have remained poorly defined. We isolated lymphatic endothelial cells (LECs) and blood vascular endothelial cells (BVECs) by immunomagnetic isolation directly from human skin. Cultured LECs but not BVECs expressed the lymphatic markers Prox1 and LYVE-1 and formed LYVE-1-positive vascular tubes after implantation in vivo. Transcriptional profiling studies revealed increased expression of several extracellular matrix and adhesion molecules in BVECs, including versican, collagens, laminin, and N-cadherin, and of the growth factor receptors endoglin and vascular endothelial growth factor receptor-1/Flt-1. Differential immunostains of human skin confirmed the blood vessel-specific expression of these genes. During embryonic development, endoglin expression was gradually down-regulated on lymphatic endothelium whereas vascular endothelial growth factor receptor-1 was absent from lymphatics. We also identified several genes with specific expression in LECs. These results demonstrate that some lineage-specific genes are only expressed during distinct developmental stages and they identify new molecular markers for blood vascular and lymphatic endothelium with important implications for future studies of vascular development and function. PMID:12547715

  5. Piperine Congeners as Inhibitors of Vascular Smooth Muscle Cell Proliferation.

    PubMed

    Mair, Christina E; Liu, Rongxia; Atanasov, Atanas G; Wimmer, Laurin; Nemetz-Fiedler, Daniel; Sider, Nadine; Heiss, Elke H; Mihovilovic, Marko D; Dirsch, Verena M; Rollinger, Judith M

    2015-08-01

    Successful vascular healing after percutaneous coronary interventions is related to the inhibition of abnormal vascular smooth muscle cell proliferation and efficient re-endothelialization. In the search for vascular smooth muscle cell anti-proliferative agents from natural sources we identified piperine (1), the main pungent constituent of the fruits from Piper nigrum (black pepper). Piperine inhibited vascular smooth muscle cell proliferation with an IC50 of 21.6 µM, as quantified by a resazurin conversion assay. Investigations of ten piperamides isolated from black pepper fruits and 15 synthesized piperine derivatives resulted in the identification of three potent vascular smooth muscle cell proliferation inhibitors: the natural alkaloid pipertipine (4), and the two synthetic derivatives (2E,4E)-N,N-dibutyl-5-(3,5-dimethoxyphenyl)penta-2,4-dienamide (14) and (E)-N,N-dibutyl-3-(naphtho[2,3-d][1,3]dioxol-5-yl)acrylamide (20). They showed IC50 values of 3.38, 6.00, and 7.85 µM, respectively. Furthermore, the synthetic compound (2E,4E)-5-(4-fluorophenyl)-1-(piperidin-1-yl)penta-2,4-dien-1-one (12) was found to be cell type selective, by inhibiting vascular smooth muscle cell proliferation with an IC50 of 11.8 µM without influencing the growth of human endothelial cells. PMID:26132851

  6. Complex patterns of abnormal heartbeats

    NASA Technical Reports Server (NTRS)

    Schulte-Frohlinde, Verena; Ashkenazy, Yosef; Goldberger, Ary L.; Ivanov, Plamen Ch; Costa, Madalena; Morley-Davies, Adrian; Stanley, H. Eugene; Glass, Leon

    2002-01-01

    Individuals having frequent abnormal heartbeats interspersed with normal heartbeats may be at an increased risk of sudden cardiac death. However, mechanistic understanding of such cardiac arrhythmias is limited. We present a visual and qualitative method to display statistical properties of abnormal heartbeats. We introduce dynamical "heartprints" which reveal characteristic patterns in long clinical records encompassing approximately 10(5) heartbeats and may provide information about underlying mechanisms. We test if these dynamics can be reproduced by model simulations in which abnormal heartbeats are generated (i) randomly, (ii) at a fixed time interval following a preceding normal heartbeat, or (iii) by an independent oscillator that may or may not interact with the normal heartbeat. We compare the results of these three models and test their limitations to comprehensively simulate the statistical features of selected clinical records. This work introduces methods that can be used to test mathematical models of arrhythmogenesis and to develop a new understanding of underlying electrophysiologic mechanisms of cardiac arrhythmia.

  7. Eye Movement and Visual Search: Are There Elementary Abnormalities in Autism?

    ERIC Educational Resources Information Center

    Brenner, Laurie A.; Turner, Katherine C.; Muller, Ralph-Axel

    2007-01-01

    Although atypical eye gaze is commonly observed in autism, little is known about underlying oculomotor abnormalities. Our review of visual search and oculomotor systems in the healthy brain suggests that relevant networks may be partially impaired in autism, given regional abnormalities known from neuroimaging. However, direct oculomotor evidence…

  8. The vascular and neurogenic factors associated with erectile dysfunction in patients after pelvic fractures

    PubMed Central

    Guan, Yong; Wendong, Sun; Zhao, Shengtian; Liu, Tongyan; Liu, Yuqiang; Zhang, Xiulin; Yuan, Mingzhen

    2015-01-01

    ABSTRACT Erectile dysfunction (ED) is a common complication of pelvic fractures. To identify the vascular and neurogenic factors associated with ED, 120 patients admitted with ED after traumatic pelvic fracture between January 2009 and June 2013 were enrolled in this study. All patients answered the International Index of Erectile Function (IIEF-5) questionnaire. Nocturnal penile tumescence (NPT) testing confirmed the occurrence of ED in 96 (80%) patients on whom penile duplex ultrasound and neurophysiological testing were further performed. Of these ED patients 29 (30%) were demonstrated only with vascular abnormality, 41 (42.7%) were detected only with neural abnormality, 26 (27.1%) revealed mixed abnormalities. Of the 55 patients (29+26) with vascular problems, 7 patients (12.7%) with abnormal arterial response to intracavernous injection of Bimix (15mg papaverine and 1mg phentolamine), 31 (56.4%) with corporal veno-occlusive dysfunction and 17 (30.9%) had both problems. Of the 67 (41+26) patients with abnormal neurophysiological outcomes, 51 (76.1%) with abnormal bulbocavernosus reflex (BCR), 20 (29.9%) with pathological pudendal nerve evoked potentials (PDEPs) and 25 (37.3%) with abnormal posterior tibial somatosensory nerve evoked potentials (PTSSEPs). Our observation indicated that neurogenic factors are important for the generation of ED in patients with pelvic fracture; venous impotence is more common than arteriogenic ED. PMID:26689522

  9. Vascular Dysfunction in Horses with Endocrinopathic Laminitis

    PubMed Central

    Morgan, Ruth A.; Keen, John A.; Walker, Brian R.; Hadoke, Patrick W. F.

    2016-01-01

    Endocrinopathic laminitis (EL) is a vascular condition of the equine hoof resulting in severe lameness with both welfare and economic implications. EL occurs in association with equine metabolic syndrome and equine Cushing’s disease. Vascular dysfunction, most commonly due to endothelial dysfunction, is associated with cardiovascular risk in people with metabolic syndrome and Cushing’s syndrome. We tested the hypothesis that horses with EL have vascular, specifically endothelial, dysfunction. Healthy horses (n = 6) and horses with EL (n = 6) destined for euthanasia were recruited. We studied vessels from the hooves (laminar artery, laminar vein) and the facial skin (facial skin arteries) by small vessel wire myography. The response to vasoconstrictors phenylephrine (10−9–10-5M) and 5-hydroxytryptamine (5HT; 10−9–10-5M) and the vasodilator acetylcholine (10−9–10-5M) was determined. In comparison with healthy controls, acetylcholine-induced relaxation was dramatically reduced in all intact vessels from horses with EL (% relaxation of healthy laminar arteries 323.5 ± 94.1% v EL 90.8 ± 4.4%, P = 0.01, laminar veins 129.4 ± 14.8% v EL 71.2 ± 4.1%, P = 0.005 and facial skin arteries 182.0 ± 40.7% v EL 91.4 ± 4.5%, P = 0.01). In addition, contractile responses to phenylephrine and 5HT were increased in intact laminar veins from horses with EL compared with healthy horses; these differences were endothelium-independent. Sensitivity to phenylephrine was reduced in intact laminar arteries (P = 0.006) and veins (P = 0.009) from horses with EL. Horses with EL exhibit significant vascular dysfunction in laminar vessels and in facial skin arteries. The systemic nature of the abnormalities suggest this dysfunction is associated with the underlying endocrinopathy and not local changes to the hoof. PMID:27684374

  10. Neuropathological diagnosis of vascular cognitive impairment and vascular dementia with implications for Alzheimer's disease.

    PubMed

    Kalaria, Raj N

    2016-05-01

    Vascular dementia (VaD) is recognised as a neurocognitive disorder, which is explained by numerous vascular causes in the general absence of other pathologies. The heterogeneity of cerebrovascular disease makes it challenging to elucidate the neuropathological substrates and mechanisms of VaD as well as vascular cognitive impairment (VCI). Consensus and accurate diagnosis of VaD relies on wide-ranging clinical, neuropsychometric and neuroimaging measures with subsequent pathological confirmation. Pathological diagnosis of suspected clinical VaD requires adequate postmortem brain sampling and rigorous assessment methods to identify important substrates. Factors that define the subtypes of VaD include the nature and extent of vascular pathologies, degree of involvement of extra and intracranial vessels and the anatomical location of tissue changes. Atherosclerotic and cardioembolic diseases appear the most common substrates of vascular brain injury or infarction. Small vessel disease characterised by arteriolosclerosis and lacunar infarcts also causes cortical and subcortical microinfarcts, which appear to be the most robust substrates of cognitive impairment. Diffuse WM changes with loss of myelin and axonal abnormalities are common to almost all subtypes of VaD. Medial temporal lobe and hippocampal atrophy accompanied by variable hippocampal sclerosis are also features of VaD as they are of Alzheimer's disease. Recent observations suggest that there is a vascular basis for neuronal atrophy in both the temporal and frontal lobes in VaD that is entirely independent of any Alzheimer pathology. Further knowledge on specific neuronal and dendro-synaptic changes in key regions resulting in executive dysfunction and other cognitive deficits, which define VCI and VaD, needs to be gathered. Hereditary arteriopathies such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy or CADASIL have provided insights into the mechanisms of

  11. Vascular Anomalies and Airway Concerns

    PubMed Central

    Clarke, Caroline; Lee, Edward I.; Edmonds, Joseph

    2014-01-01

    Vascular anomalies, both tumors and malformations, can occur anywhere in the body, including the airway, often without any external manifestations. However, vascular anomalies involving the airway deserve special consideration as proper recognition and management can be lifesaving. In this article, the authors discuss vascular anomalies as they pertains to the airway, focusing on proper diagnosis, diagnostic modalities, and therapeutic options. PMID:25045336

  12. Infrared thermal imaging for detection of peripheral vascular disorders.

    PubMed

    Bagavathiappan, S; Saravanan, T; Philip, John; Jayakumar, T; Raj, Baldev; Karunanithi, R; Panicker, T M R; Korath, M Paul; Jagadeesan, K

    2009-01-01

    Body temperature is a very useful parameter for diagnosing diseases. There is a definite correlation between body temperature and diseases. We have used Infrared Thermography to study noninvasive diagnosis of peripheral vascular diseases. Temperature gradients are observed in the affected regions of patients with vascular disorders, which indicate abnormal blood flow in the affected region. Thermal imaging results are well correlated with the clinical findings. Certain areas on the affected limbs show increased temperature profiles, probably due to inflammation and underlying venous flow changes. In general the temperature contrast in the affected regions is about 0.7 to 1 degrees C above the normal regions, due to sluggish blood circulation. The results suggest that the thermal imaging technique is an effective technique for detecting small temperature changes in the human body due to vascular disorders.

  13. The Vascular Depression Hypothesis: Mechanisms Linking Vascular Disease with Depression

    PubMed Central

    Taylor, Warren D.; Aizenstein, Howard J.; Alexopoulos, George S.

    2013-01-01

    The ‘Vascular Depression’ hypothesis posits that cerebrovascular disease may predispose, precipitate, or perpetuate some geriatric depressive syndromes. This hypothesis stimulated much research that has improved our understanding of the complex relationships between late-life depression (LLD), vascular risk factors, and cognition. Succinctly, there are well-established relationships between late-life depression, vascular risk factors, and cerebral hyperintensities, the radiological hallmark of vascular depression. Cognitive dysfunction is common in late-life depression, particularly executive dysfunction, a finding predictive of poor antidepressant response. Over time, progression of hyperintensities and cognitive deficits predicts a poor course of depression and may reflect underlying worsening of vascular disease. This work laid the foundation for examining the mechanisms by which vascular disease influences brain circuits and influences the development and course of depression. We review data testing the vascular depression hypothesis with a focus on identifying potential underlying vascular mechanisms. We propose a disconnection hypothesis, wherein focal vascular damage and white matter lesion location is a crucial factor influencing neural connectivity that contributes to clinical symptomatology. We also propose inflammatory and hypoperfusion hypotheses, concepts that link underlying vascular processes with adverse effects on brain function that influence the development of depression. Testing such hypotheses will not only inform the relationship between vascular disease and depression but also provide guidance on the potential repurposing of pharmacological agents that may improve late-life depression outcomes. PMID:23439482

  14. Electrocardiograph abnormalities in intracerebral hemorrhage.

    PubMed

    Takeuchi, Satoru; Nagatani, Kimihiro; Otani, Naoki; Wada, Kojiro; Mori, Kentaro

    2015-12-01

    This study investigated the prevalence and type of electrocardiography (ECG) abnormalities, and their possible association with the clinical/radiological findings in 118 consecutive patients with non-traumatic, non-neoplastic intracerebral hemorrhage (ICH). ECG frequently demonstrates abnormalities in patients with ischemic stroke and subarachnoid hemorrhage, but little is known of ECG changes in ICH patients. Clinical and radiological information was retrospectively reviewed. ECG recordings that were obtained within 24 hours of the initial hemorrhage were analyzed. Sixty-six patients (56%) had one or more ECG abnormalities. The most frequent was ST depression (24%), followed by left ventricular hypertrophy (20%), corrected QT interval (QTc) prolongation (19%), and T wave inversion (19%). The logistic regression analysis demonstrated the following: insular involvement was an independent predictive factor of ST depression (p<0.001; odds ratio OR 10.18; 95% confidence interval [CI] 2.84-36.57); insular involvement (p<0.001; OR 23.98; 95% CI 4.91-117.11) and presence of intraventricular hemorrhage (p<0.001; OR 8.72; 95% CI 2.69-28.29) were independent predictive factors of QTc prolongation; deep hematoma location (p<0.001; OR 19.12; 95% CI 3.82-95.81) and hematoma volume >30 ml (p=0.001; OR 6.58; 95% CI 2.11-20.46) were independent predictive factors of T wave inversion. We demonstrate associations between ECG abnormalities and detailed characteristics of ICH.

  15. Cerebral oxygenation and optimal vascular brain organization

    PubMed Central

    Hadjistassou, Constantinos; Bejan, Adrian; Ventikos, Yiannis

    2015-01-01

    The cerebral vascular network has evolved in such a way so as to minimize transport time and energy expenditure. This is accomplished by a subtle combination of the optimal arrangement of arteries, arterioles and capillaries and the transport mechanisms of convection and diffusion. Elucidating the interaction between cerebral vascular architectonics and the latter physical mechanisms can catalyse progress in treating cerebral pathologies such as stroke, brain tumours, dementia and targeted drug delivery. Here, we show that brain microvascular organization is predicated on commensurate intracapillary oxygen convection and parenchymal diffusion times. Cross-species grey matter results for the rat, cat, rabbit and human reveal very good correlation between the cerebral capillary and tissue mean axial oxygen convective and diffusion time intervals. These findings agree with the constructal principle. PMID:25972435

  16. Vascular Biology of the Biliary Epithelium

    PubMed Central

    Morell, Carola M.; Fabris, Luca; Strazzabosco, Mario

    2012-01-01

    Cholangiocytes are involved in a variety of processes essential for liver pathophysiology. To meet their demanding metabolic and functional needs, bile ducts are nourished by an own arterial supply, the peribiliary plexus. This capillary network originates from the hepatic artery and is strictly arranged around the intrahepatic bile ducts. Biliary and vascular structures are linked by a close anatomic and functional association necessary for liver development, normal organ physiology and liver repair. This strong association is finely regulated by a range of angiogenic signals, enabling the crosstalk between cholangiocytes and the different vascular cell types. This review will briefly illustrate the “vascular” properties of cholangiocytes, their underlying molecular mechanisms and the relevant pathophysiological settings. PMID:23855292

  17. Vascular cognitive impairment and dementia.

    PubMed

    Gorelick, Philip B; Counts, Scott E; Nyenhuis, David

    2016-05-01

    Vascular contributions to cognitive impairment are receiving heightened attention as potentially modifiable factors for dementias of later life. These factors have now been linked not only to vascular cognitive disorders but also Alzheimer's disease. In this chapter we review 3 related topics that address vascular contributions to cognitive impairment: 1. vascular pathogenesis and mechanisms; 2. neuropsychological and neuroimaging phenotypic manifestations of cerebrovascular disease; and 3. prospects for prevention of cognitive impairment of later life based on cardiovascular and stroke risk modification. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. PMID:26704177

  18. Plant Vascular Biology 2010

    SciTech Connect

    Ding, Biao

    2014-11-17

    This grant supported the Second International Conference on Plant Vascular Biology (PVB 2010) held July 24-28, 2010 on the campus of Ohio State University, Columbus, Ohio. Biao Ding (Ohio State University; OSU) and David Hannapel (Iowa State University; ISU) served as co-chairs of this conference. Biao Ding served as the local organizer. PVB is defined broadly here to include studies on the biogenesis, structure and function of transport systems in plants, under conditions of normal plant growth and development as well as of plant interactions with pathogens. The transport systems cover broadly the xylem, phloem, plasmodesmata and vascular cell membranes. The PVB concept has emerged in recent years to emphasize the integrative nature of the transport systems and approaches to investigate them.

  19. [Vascular variability syndromes].

    PubMed

    Otsuka, Kuniaki; Okajima, Kiyotaka; Yamanaka, Takashi; Cornelissen, Germaine

    2014-08-01

    Analytical global and local methods applied to human blood pressure (BP) records of around-the-clock measurements. The chronobiological interpretation of ambulatory BP monitoring records in the light of time-specified reference values derived from healthy peers matched by sex and age identify vascular variability disorders (VVDs) for an assessment of cardio-, cerebro-, and renovascular disease risk. VVD includes circadian BP over-swinging (CHAT, short for circadian hyper-amplitude tension), deficient heart rate variability, MESOR (midline-estimating statistic of rhythm) hypertension, excessively elevated pulse pressure over 60 mmHg, BP ecphasia (an odd timing of the circadian rhythms in BP but not in that of heart rate) and frequency alteration. The term MESOR-hypertension indicates only one of several VVDs that can combine to for sets of 2, 3 and n-component vascular variability syndromes. PMID:25167758

  20. [Vascular endothelial Barrier Function].

    PubMed

    Ivanov, A N; Puchinyan, D M; Norkin, I A

    2015-01-01

    Endothelium is an important regulator of selective permeability of the vascular wall for different molecules and cells. This review summarizes current data on endothelial barrier function. Endothelial glycocalyx structure, its function and role in the molecular transport and leukocytes migration across the endothelial barrier are discussed. The mechanisms of transcellular transport of macromolecules and cell migration through endothelial cells are reviewed. Special section of this article addresses the structure and function of tight and adherens endothelial junction, as well as their importance for the regulation of paracellular transport across the endothelial barrier. Particular attention is paid to the signaling mechanism of endothelial barrier function regulation and the factors that influence on the vascular permeability.

  1. Vascular Cambium Development

    PubMed Central

    Nieminen, Kaisa; Blomster, Tiina; Helariutta, Ykä; Mähönen, Ari Pekka

    2015-01-01

    Secondary phloem and xylem tissues are produced through the activity of vascular cambium, the cylindrical secondary meristem which arises among the primary plant tissues. Most dicotyledonous species undergo secondary development, among them Arabidopsis. Despite its small size and herbaceous nature, Arabidopsis displays prominent secondary growth in several organs, including the root, hypocotyl and shoot. Together with the vast genetic resources and molecular research methods available for it, this has made Arabidopsis a versatile and accessible model organism for studying cambial development and wood formation. In this review, we discuss and compare the development and function of the vascular cambium in the Arabidopsis root, hypocotyl, and shoot. We describe the current understanding of the molecular regulation of vascular cambium and compare it to the function of primary meristems. We conclude with a look at the future prospects of cambium research, including opportunities provided by phenotyping and modelling approaches, complemented by studies of natural variation and comparative genetic studies in perennial and woody plant species. PMID:26078728

  2. Congenital Vascular Anomalies.

    PubMed

    Gravereaux, Edwin C.; Nguyen, Louis L.; Cunningham, Leslie D.

    2004-04-01

    Congenital vascular anomalies are rare. The cardiovascular specialist should nevertheless be aware of the more common types of vascular anomalies and understand the implications for patient treatment and the likelihood of associated morbidity. The presentation of congenital arteriovenous malformations can range from asymptomatic or cosmetic lesions, to those causing ischemia, ulceration, hemorrhage, or high-output congestive heart failure. Treatment of large, symptomatic arteriovenous malformations often requires catheter-directed embolization prior to the attempt at complete surgical excision. Later recurrence, due to collateral recruitment, is frequent. Graded compression stockings and leg elevation are the mainstays of treatment for the predominantly venous congenital vascular anomalies. Most congenital central venous disorders are clinically silent. An exception is the retrocaval ureter. Retroaortic left renal vein, circumaortic venous ring, and absent, left-sided or duplicated inferior vena cava are relevant when aortic or inferior vena cava procedures are planned. The treatment of the venous disorders is directed at prevention or management of symptoms. Persistent sciatic artery, popliteal entrapment syndrome, and aberrant right subclavian artery origin are congenital anomalies that are typically symptomatic at presentation. Because they mimic more common diseases, diagnosis is frequently delayed. Delay can result in significant morbidity for the patient. Failure to make the diagnosis of persistent sciatic artery and popliteal entrapment can result in critical limb ischemia and subsequent amputation. Unrecognized aberrant right subclavian artery origin associated with aneurysmal degeneration can rupture and result in death. The treatment options for large-vessel arterial anomalies are surgical, sometimes in combination with endovascular techniques.

  3. Vascular Guidance: Microstructural Scaffold Patterning for Inductive Neovascularization

    PubMed Central

    Muller, Daniel; Chim, Harvey; Bader, Augustinus; Whiteman, Matthew; Schantz, Jan-Thorsten

    2011-01-01

    Current tissue engineering techniques are limited by inadequate vascularisation and perfusion of cell-scaffold constructs. Microstructural patterning through biomimetic vascular channels within a polymer scaffold might induce neovascularization, allowing fabrication of large engineered constructs. The network of vascular channels within a frontal-parietal defect in a patient, originating from the anterior branch of the middle meningeal artery, was modeled using computer-aided design (CAD) techniques and subsequently incorporated into polycaprolactone (PCL) scaffolds fabricated using fused deposition modeling (FDM). Bone marrow-derived mesenchymal stem cells (MSCs) were seeded onto the scaffolds and implanted into a rat model, with an arteriovenous bundle inserted at the proximal extent of the vascular network. After 3 weeks, scaffolds were elevated as a prefabricated composite tissue-polymer flap and transferred using microsurgical technique. Histological examination of explanted scaffolds revealed vascular ingrowth along patterned channels, with abundant capillary and connective tissue formation throughout experimental scaffolds, while control scaffolds showed only granulation tissue. All prefabricated constructs transferred as free flaps survived and were viable. We term this concept “vascular guidance,” whereby neovascularization is guided through customized channels in a scaffold. Our technique might potentially allow fabrication of much larger tissue-engineered constructs than current technologies allow, as well as allowing tailored construct fabrication with a patient-specific vessel network based on CT scan data and CAD technology. PMID:21188080

  4. Vascular tissue engineering by computer-aided laser micromachining.

    PubMed

    Doraiswamy, Anand; Narayan, Roger J

    2010-04-28

    Many conventional technologies for fabricating tissue engineering scaffolds are not suitable for fabricating scaffolds with patient-specific attributes. For example, many conventional technologies for fabricating tissue engineering scaffolds do not provide control over overall scaffold geometry or over cell position within the scaffold. In this study, the use of computer-aided laser micromachining to create scaffolds for vascular tissue networks was investigated. Computer-aided laser micromachining was used to construct patterned surfaces in agarose or in silicon, which were used for differential adherence and growth of cells into vascular tissue networks. Concentric three-ring structures were fabricated on agarose hydrogel substrates, in which the inner ring contained human aortic endothelial cells, the middle ring contained HA587 human elastin and the outer ring contained human aortic vascular smooth muscle cells. Basement membrane matrix containing vascular endothelial growth factor and heparin was to promote proliferation of human aortic endothelial cells within the vascular tissue networks. Computer-aided laser micromachining provides a unique approach to fabricate small-diameter blood vessels for bypass surgery as well as other artificial tissues with complex geometries.

  5. Vascular tissue engineering by computer-aided laser micromachining.

    PubMed

    Doraiswamy, Anand; Narayan, Roger J

    2010-04-28

    Many conventional technologies for fabricating tissue engineering scaffolds are not suitable for fabricating scaffolds with patient-specific attributes. For example, many conventional technologies for fabricating tissue engineering scaffolds do not provide control over overall scaffold geometry or over cell position within the scaffold. In this study, the use of computer-aided laser micromachining to create scaffolds for vascular tissue networks was investigated. Computer-aided laser micromachining was used to construct patterned surfaces in agarose or in silicon, which were used for differential adherence and growth of cells into vascular tissue networks. Concentric three-ring structures were fabricated on agarose hydrogel substrates, in which the inner ring contained human aortic endothelial cells, the middle ring contained HA587 human elastin and the outer ring contained human aortic vascular smooth muscle cells. Basement membrane matrix containing vascular endothelial growth factor and heparin was to promote proliferation of human aortic endothelial cells within the vascular tissue networks. Computer-aided laser micromachining provides a unique approach to fabricate small-diameter blood vessels for bypass surgery as well as other artificial tissues with complex geometries. PMID:20308108

  6. Efficient in vivo Vascularization of Tissue Engineering Scaffolds

    PubMed Central

    Hegen, Anja; Blois, Anna; Tiron, Crina E.; Hellesøy, Monica; Micklem, David R.; Nör, Jacques E.; Akslen, Lars A.; Lorens, James B.

    2010-01-01

    The success of tissue engineering depends on the rapid and efficient formation of a functional blood vasculature. Adult blood vessels comprise endothelial cells and peri-vascular mural cells that assemble into patent tubules ensheathed by a basement membrane during angiogenesis. Using individual vessel components, we characterized intra-scaffold microvessel self-assembly efficiency in a physiological in vivo tissue engineering implant context. Primary human microvascular endothelial- and vascular smooth muscle cells were seeded at different ratios in poly-L lactic acid (PLLA) scaffolds enriched with basement membrane proteins (Matrigel) and implanted subcutaneously into immunocompromised mice. Temporal intra-scaffold microvessel formation, anastomosis and perfusion were monitored by immunohistochemical, flow cytometric and in vivo multiphoton fluorescence microscopy analysis. Vascularization in the tissue engineering context was strongly enhanced in the implants seeded with a complete complement of blood vessel components: Human microvascular endothelial and vascular smooth muscle cells in vivo assembled a patent microvasculature within Matrigel-enriched PLLA scaffolds that anastomosed with the host circulation during the first week of implantation. Multiphoton fluorescence angiographic analysis of the intra-scaffold microcirculation showed a uniform, branched microvascular network. 3-D image reconstruction analysis of hPASMC distribution within vascularized implants was non-random and displayed a preferential peri-vascular localization. Hence, efficient microvessel self-assembly, anastomosis and establishment of a functional microvasculture in the native hypoxic in vivo tissue engineering context is promoted by providing a complete set of vascular components. PMID:20865694

  7. Multi-modality imaging review of congenital abnormalities of kidney and upper urinary tract

    PubMed Central

    Ramanathan, Subramaniyan; Kumar, Devendra; Khanna, Maneesh; Al Heidous, Mahmoud; Sheikh, Adnan; Virmani, Vivek; Palaniappan, Yegu

    2016-01-01

    Congenital abnormalities of the kidney and urinary tract (CAKUT) include a wide range of abnormalities ranging from asymptomatic ectopic kidneys to life threatening renal agenesis (bilateral). Many of them are detected in the antenatal or immediate postnatal with a significant proportion identified in the adult population with varying degree of severity. CAKUT can be classified on embryological basis in to abnormalities in the renal parenchymal development, aberrant embryonic migration and abnormalities of the collecting system. Renal parenchymal abnormalities include multi cystic dysplastic kidneys, renal hypoplasia, number (agenesis or supernumerary), shape and cystic renal diseases. Aberrant embryonic migration encompasses abnormal location and fusion anomalies. Collecting system abnormalities include duplex kidneys and Pelvi ureteric junction obstruction. Ultrasonography (US) is typically the first imaging performed as it is easily available, non-invasive and radiation free used both antenatally and postnatally. Computed tomography (CT) and magnetic resonance imaging (MRI) are useful to confirm the ultrasound detected abnormality, detection of complex malformations, demonstration of collecting system and vascular anatomy and more importantly for early detection of complications like renal calculi, infection and malignancies. As CAKUT are one of the leading causes of end stage renal disease, it is important for the radiologists to be familiar with the varying imaging appearances of CAKUT on US, CT and MRI, thereby helping in prompt diagnosis and optimal management. PMID:26981222

  8. Multi-modality imaging review of congenital abnormalities of kidney and upper urinary tract.

    PubMed

    Ramanathan, Subramaniyan; Kumar, Devendra; Khanna, Maneesh; Al Heidous, Mahmoud; Sheikh, Adnan; Virmani, Vivek; Palaniappan, Yegu

    2016-02-28

    Congenital abnormalities of the kidney and urinary tract (CAKUT) include a wide range of abnormalities ranging from asymptomatic ectopic kidneys to life threatening renal agenesis (bilateral). Many of them are detected in the antenatal or immediate postnatal with a significant proportion identified in the adult population with varying degree of severity. CAKUT can be classified on embryological basis in to abnormalities in the renal parenchymal development, aberrant embryonic migration and abnormalities of the collecting system. Renal parenchymal abnormalities include multi cystic dysplastic kidneys, renal hypoplasia, number (agenesis or supernumerary), shape and cystic renal diseases. Aberrant embryonic migration encompasses abnormal location and fusion anomalies. Collecting system abnormalities include duplex kidneys and Pelvi ureteric junction obstruction. Ultrasonography (US) is typically the first imaging performed as it is easily available, non-invasive and radiation free used both antenatally and postnatally. Computed tomography (CT) and magnetic resonance imaging (MRI) are useful to confirm the ultrasound detected abnormality, detection of complex malformations, demonstration of collecting system and vascular anatomy and more importantly for early detection of complications like renal calculi, infection and malignancies. As CAKUT are one of the leading causes of end stage renal disease, it is important for the radiologists to be familiar with the varying imaging appearances of CAKUT on US, CT and MRI, thereby helping in prompt diagnosis and optimal management. PMID:26981222

  9. Functional properties of ion channels and transporters in tumour vascularization

    PubMed Central

    Fiorio Pla, Alessandra; Munaron, Luca

    2014-01-01

    Vascularization is crucial for solid tumour growth and invasion, providing metabolic support and sustaining metastatic dissemination. It is now accepted that ion channels and transporters play a significant role in driving the cancer growth at all stages. They may represent novel therapeutic, diagnostic and prognostic targets for anti-cancer therapies. On the other hand, although the expression and role of ion channels and transporters in the vascular endothelium is well recognized and subject of recent reviews, only recently has their involvement in tumour vascularization been recognized. Here, we review the current literature on ion channels and transporters directly involved in the angiogenic process. Particular interest will be focused on tumour angiogenesis in vivo as well as in the different steps that drive this process in vitro, such as endothelial cell proliferation, migration, adhesion and tubulogenesis. Moreover, we compare the ‘transportome’ system of tumour vascular network with the physiological one. PMID:24493751

  10. Rabbit tibial periosteum and saphenous arteriovenous vascular bundle as an in vivo bioreactor to construct vascularized tissue-engineered bone: a feasibility study.

    PubMed

    Han, Dong; Guan, Xiaoyi; Wang, Jian; Wei, Jiao; Li, Qingfeng

    2014-02-01

    The aim of this project was to construct vascularized tissue-engineered living bone with an autologous vascular network by means of a rabbit bioreactor in vivo. The key components of the in vivo bioreactor for bone formation were the vascularized tibial periosteum and the saphenous vascular bundle. Beta-tricalcium phosphate (β-TCP) scaffolds were implanted into the in vivo bioreactor (vascular pedicle implantation and vascularized periosteum encapsulation). At 4 weeks postsurgery, new bone formation was mainly "cartilage-bone inducing" in the inner periosteum, and was primarily seen in the outer aspects of the scaffold with some amount in the middle part as well. Microvascular infusion showed that direct revascularization of β-TCP was obtained by means of vascular implantation. Triple staining results showed a large amount of blue collagen fibers. Vascular endothelial growth factor immunohistochemical staining displayed endothelial cells of new blood vessels in bone tissue. The bioreactor established in this study can be used to prepare tissue-engineered bone with a vascular network.

  11. Digital image processing of vascular angiograms

    NASA Technical Reports Server (NTRS)

    Selzer, R. H.; Beckenbach, E. S.; Blankenhorn, D. H.; Crawford, D. W.; Brooks, S. H.

    1975-01-01

    The paper discusses the estimation of the degree of atherosclerosis in the human femoral artery through the use of a digital image processing system for vascular angiograms. The film digitizer uses an electronic image dissector camera to scan the angiogram and convert the recorded optical density information into a numerical format. Another processing step involves locating the vessel edges from the digital image. The computer has been programmed to estimate vessel abnormality through a series of measurements, some derived primarily from the vessel edge information and others from optical density variations within the lumen shadow. These measurements are combined into an atherosclerosis index, which is found in a post-mortem study to correlate well with both visual and chemical estimates of atherosclerotic disease.

  12. Using the Vascular Quality Initiative to improve quality of care and patient outcomes for vascular surgery patients.

    PubMed

    Bensley, Rodney P; Beck, Adam W

    2015-06-01

    The Society for Vascular Surgery Vascular Quality Initiative (VQI) is a collaborative network of vascular specialists from various specialties that seeks to improve the quality and safety of vascular care by sharing data among physicians, medical centers, and regions. Working under a Patient Safety Organization designation by the Agency for Healthcare Research and Quality, the VQI provides a protected environment where data can be pooled and evaluated for trends that might provide opportunities to improve the care we provide our patients. Since its inception in 2011, this national organization has grown rapidly and now involves >300 medical centers that are separated into 18 active regional groups who meet twice yearly to discuss quality improvement. The structure of the VQI provides a powerful platform for data collection and analysis, and has allowed the development of a large body of literature that demonstrates the importance and benefits of participation. Here we provide a brief overview of the VQI to date.

  13. Retinal vascular changes are a marker for cerebral vascular diseases

    PubMed Central

    Moss, Heather E.

    2016-01-01

    The retinal circulation is a potential marker of cerebral vascular disease because it shares origin and drainage with the intracranial circulation and because it can be directly visualized using ophthalmoscopy. Cross sectional and cohort studies have demonstrated associations between chronic retinal and cerebral vascular disease, acute retinal and cerebral vascular disease and chronic retinal vascular disease and acute cerebral vascular disease. In particular, certain qualitative features of retinopathy, retinal artery occlusion and increased retinal vein caliber are associated with concurrent and future cerebrovascular events. These associations persist after accounting for confounding variables known to be disease-causing in both circulations, which supports the potential use of retinal vasculature findings to stratify individuals with regards to cerebral vascular disease risk. PMID:26008809

  14. [Transient abnormal Q-waves].

    PubMed

    Godballe, C; Hoeck, H C; Sørensen, J A

    1990-01-01

    We present a case of transient abnormal Q-waves (TAQ) and a review of the literature. TAQ are defined as abnormal Q-waves, which disappear within ten days. They are most often seen in patients with ischemic heart disease (IHD) but are also seen in other conditions. Brief episodes of myocardial ischemia giving rise to reversible biochemical and ultrastructural myocardial changes, resulting in transient ECG changes, provide an accepted theory for the pathogenesis of TAO. Investigations have shown that the occurrence of exercise-induced TAQ may be a symptom of IHD. It is impossible to distinguish TAQ from Q-waves induced by myocardial infarction. Appearance of TAQ during exercise-testing frequently indicates IHD. PMID:2301045

  15. [Chromosome abnormalities in human cancer].

    PubMed

    Salamanca-Gómez, F

    1995-01-01

    Recent investigation on the presence of chromosome abnormalities in neoplasias has allowed outstanding advances in the knowledge of malignant transformation mechanisms and important applications in the clinical diagnosis and prognosis of leukaemias, lymphomas and solid tumors. The purpose of the present paper is to discuss the most relevant cytogenetic aberrations, some of them described at the Unidad de Investigación Médica en Genética Humana, Instituto Mexicano del Seguro Social, and to correlate these abnormalities with recent achievements in the knowledge of oncogenes, suppressor genes or antioncogenes, their chromosome localization, and their mutations in human neoplasia; as well as their perspectives in prevention and treatment of cancer that such findings permit to anticipate.

  16. Comparative characterization of stromal vascular cells derived from three types of vascular wall and adipose tissue.

    PubMed

    Yang, Santsun; Eto, Hitomi; Kato, Harunosuke; Doi, Kentaro; Kuno, Shinichiro; Kinoshita, Kahori; Ma, Hsu; Tsai, Chi-Han; Chou, Wan-Ting; Yoshimura, Kotaro

    2013-12-01

    Multipotent stem/progenitor cells localize perivascularly in many organs and vessel walls. These tissue-resident stem/progenitor cells differentiate into vascular endothelial cells, pericytes, and other mesenchymal lineages, and participate in physiological maintenance and repair of vasculatures. In this study, we characterized stromal vascular cells obtained through the explant culture method from three different vessel walls in humans: arterial wall (ART; >500 μm in diameter), venous wall (VN; >500 μm in diameter), and small vessels in adipose tissue (SV; arterioles and venules, <100 μm in diameter). These were examined for functionality and compared with adipose-derived stem/stromal cells (ASCs). All stromal vascular cells of different origins presented fibroblast-like morphology and we could not visually discriminate one population from another. Flow cytometry showed that the cultured population heterogeneously expressed a variety of surface antigens associated with stem/progenitor cells, but CD105 was expressed by most cells in all groups, suggesting that the cells generally shared the characteristics of mesenchymal stem cells. Our histological and flow cytometric data suggested that the main population of vessel wall-derived stromal vascular cells were CD34(+)/CD31(-) and came from the tunica adventitia and areola tissue surrounding the adventitia. CD271 (p75NTR) was expressed by the vasa vasorum in the VN adventitia and by a limited population in the adventitia of SV. All three populations differentiated into multiple lineages as did ASCs. ART cells induced the largest quantity of calcium formation in the osteogenic medium, whereas ASCs showed the greatest adipogenic differentiation. SV and VN stromal cells had greater potency for network formation than did ART stromal cells. In conclusion, the three stromal vascular populations exhibited differential functional properties. Our results have clinical implications for vascular diseases such as

  17. Ultrasound screening for fetal abnormalities.

    PubMed

    Chitty, L S

    1995-12-01

    Ultrasound screening for fetal abnormalities is increasingly becoming part of routine antenatal care in Europe and the UK. However, there has been very little formal evaluation of this practice. In this article reports of routine ultrasound screening are reviewed and the advantages and disadvantages discussed. The majority of routine anomaly scanning is done in the second trimester but there may be a case for screening at other times in pregnancy and alternative anomaly screening policies are discussed. PMID:8710765

  18. [Endocrine abnormalities in HIV infections].

    PubMed

    Verges, B; Chavanet, P; Desgres, J; Kisterman, J P; Waldner, A; Vaillant, G; Portier, H; Brun, J M; Putelat, R

    The finding of endocrine gland lesions at pathological examination in AIDS and reports of several cases of endocrine disease in patients with this syndrome have prompted us to study endocrine functions in 63 patients (51 men, 12 women) with HIV-1 infection. According to the Center for Disease Control (CDC) classification system, 13 of these patients were stage CDC II, 27 stage CDC III and 23 stage CDC IV. We explored the adrenocortical function (ACTH, immediate tetracosactrin test) and the thyroid function (free T3 and T4 levels, TRH on TSH test) in all 63 patients. The hypothalamic-pituitary-gonadal axis (testosterone levels, LHRH test) and prolactin secretion (THR test) were explored in the 51 men. The results obtained showed early peripheral testicular insufficiency at stage CDC II and early pituitary gland abnormalities with hypersecretion of ACTH and prolactin also at stage CDC II. On the other hand, adrenocortical and pituitary abnormalities were not frequently found. The physiopathology of the endocrine abnormalities observed in HIV-1-infected patients remains unclear, but one may suspect that it involves interleukin-1 since this protein factor has recently been shown to stimulate the corticotropin-releasing hormone secretion and to act directly on the glycoprotein capsule of the virus (gp 120) whose structure is similar to that of some neurohormones.

  19. Fascia and Primo Vascular System.

    PubMed

    Yang, Chun; Du, Yi-Kuan; Wu, Jian-Bin; Wang, Jun; Luan, Ping; Yang, Qin-Lao; Yuan, Lin

    2015-01-01

    The anatomical basis for the concept of acupuncture points/meridians in traditional Chinese medicine (TCM) has not been resolved. This paper reviews the fascia research progress and the relationship among acupuncture points/meridians, primo vascular system (PVS), and fascia. Fascia is as a covering, with common origins of layers of the fascial system despite diverse names for individual parts. Fascia assists gliding and fluid flow and holds memory and is highly innervated. Fascia is intimately involved with nourishment of all cells of the body, including those of disease and cancer. The human body's fascia network may be the physical substrate represented by the meridians of TCM. The PVS is a newly found circulatory system; recent increased interest has led to new research and new discoveries in the anatomical and functional aspects of the PVS. The fasciology theory provides new insights into the physiological effects of acupuncture needling on basic cellular mechanisms including connective tissue mechanotransduction and regeneration. This view represents a theoretical basis and means for applying modern biomedical research to examining TCM principles and therapies, and it favors a holistic approach to diagnosis and treatment.

  20. Incretin-Based Therapy for Prevention of Diabetic Vascular Complications

    PubMed Central

    Mima, Akira

    2016-01-01

    Diabetic vascular complications are the most common cause of mortality and morbidity worldwide, with numbers of affected individuals steadily increasing. Diabetic vascular complications can be divided into two categories: macrovascular andmicrovascular complications. Macrovascular complications include coronary artery diseaseand cerebrovascular disease, while microvascular complications include retinopathy and chronic kidney disease. These complications result from metabolic abnormalities, including hyperglycemia, elevated levels of free fatty acids, and insulin resistance. Multiple mechanisms have been proposed to mediate the adverse effects of these metabolic disorders on vascular tissues, including stimulation of protein kinase C signaling and activation of the polyol pathway by oxidative stress and inflammation. Additionally, the loss of tissue-specific insulin signaling induced by hyperglycemia and toxic metabolites can induce cellular dysfunction and both macro- and microvascular complications characteristic of diabetes. Despite these insights, few therapeutic methods are available for the management of diabetic complications. Recently, incretin-based therapeutic agents, such as glucagon-like peptide-1 and dipeptidyl peptidase-4 inhibitors, have been reported to elicit vasotropic actions, suggesting a potential for effecting an actual reduction in diabetic vascular complications. The present review will summarize the relationship between multiple adverse biological mechanisms in diabetes and putative incretin-based therapeutic interventions intended to prevent diabetic vascular complications. PMID:26881236

  1. Insular and caudate lesions release abnormal yawning in stroke patients.

    PubMed

    Krestel, Heinz; Weisstanner, Christian; Hess, Christian W; Bassetti, Claudio L; Nirkko, Arto; Wiest, Roland

    2015-03-01

    Abnormal yawning is an underappreciated phenomenon in patients with ischemic stroke. We aimed at identifying frequently affected core regions in the supratentorial brain of stroke patients with abnormal yawning and contributing to the anatomical network concept of yawning control. Ten patients with acute anterior circulation stroke and ≥3 yawns/15 min without obvious cause were analyzed. The NIH stroke scale (NIHSS), Glasgow Coma Scale (GCS), symptom onset, period with abnormal yawning, blood oxygen saturation, glucose, body temperature, blood pressure, heart rate, and modified Rankin scale (mRS) were assessed for all patients. MRI lesion maps were segmented on diffusion-weighted images, spatially normalized, and the extent of overlap between the different stroke patterns was determined. Correlations between the period with abnormal yawning and the apparent diffusion coefficient (ADC) in the overlapping regions, total stroke volume, NIHSS and mRS were performed. Periods in which patients presented with episodes of abnormal yawning lasted on average for 58 h. Average GCS, NIHSS, and mRS scores were 12.6, 11.6, and 3.5, respectively. Clinical parameters were within normal limits. Ischemic brain lesions overlapped in nine out of ten patients: in seven patients in the insula and in seven in the caudate nucleus. The decrease of the ADC within the lesions correlated with the period with abnormal yawing (r = -0.76, Bonferroni-corrected p = 0.02). The stroke lesion intensity of the common overlapping regions in the insula and the caudate nucleus correlates with the period with abnormal yawning. The insula might be the long sought-after brain region for serotonin-mediated yawning.

  2. Vascular contributions to cognitive impairment, clinical Alzheimer's disease, and dementia in older persons.

    PubMed

    Kapasi, A; Schneider, J A

    2016-05-01

    There is growing evidence suggesting that vascular pathologies and dysfunction play a critical role in cognitive impairment, clinical Alzheimer's disease, and dementia. Vascular pathologies such as macroinfarcts, microinfarcts, microbleeds, small and large vessel cerebrovascular disease, and white matter disease are common especially in the brains of older persons where they contribute to cognitive impairment and lower the dementia threshold. Vascular dysfunction resulting in decreased cerebral blood flow, and abnormalities in the blood brain barrier may also contribute to the Alzheimer's disease (AD) pathophysiologic process and AD dementia. This review provides a clinical-pathological perspective on the role of vessel disease, vascular brain injury, alterations of the neurovascular unit, and mixed pathologies in the Alzheimer's disease pathophysiologic process and Alzheimer's dementia. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. PMID:26769363

  3. The association between vibration and vascular injury in rheumatic diseases: a review of the literature.

    PubMed

    Wang, Yu-Jie; Huang, Xiao-Lei; Yan, Jun-Wei; Wan, Ya-Nan; Wang, Bing-Xiang; Tao, Jin-Hui; Chen, Bing; Li, Bao-Zhu; Yang, Guo-Jun; Wang, Jing

    2015-02-01

    Vascular manifestations can be seen early in the pathogenesis of inflammatory rheumatic diseases. Animal experiments, laboratory and clinical findings indicated that acute or long-term vibration exposure can induce vascular abnormalities. Recent years, in addition to Raynaud's phenomenon (RP), vibration as a risk factor for other rheumatic diseases has also received corresponding considered. This review is concentrated upon the role of vibration in the disease of systemic sclerosis (SSc). In this review, we are going to discuss the main mechanisms which are thought to be important in pathophysiology of vascular injury under the three broad headings of "vascular", "neural" and "intravascular". Aspects on the vibration and vascular inflammation are briefly discussed. And the epidemiological studies related to vibration studies in SSc and other rheumatic diseases are taken into account.

  4. Self-contained diffuse optical imaging system for real-time detection and localization of vascular occlusions.

    PubMed

    Pollonini, Luca; Forseth, Kiefer J; Dacso, Clifford C; Parazynski, Scott E; Friedman, Jeffrey D

    2015-08-01

    Free flap surgery is a procedure where healthy tissue is transferred from a donor site to a recipient site of the body to fill a defect without maintaining the original blood supply to the flap. The anastomosis of the vascular network of the flap to the blood vessels adjacent to the recipient site has associated risks of arterial and/or venous occlusions that must be promptly detected to avoid temporary or permanent tissue damage. In this work, we present a skin-contact diffusion optical imaging (DOI) system able to continuously provide a three-dimensional representation of the flap oxygenation to promptly detect vascular occlusions potentially occurring in the flap. Multiple near-infrared LEDs and photodetectors were embedded into a self-contained optical sensor for prolonged monitoring of concentration changes of oxygenated (HbO) and deoxygenated hemoglobin (HbR) at multiple locations and depths. A time-efficient algorithm mapped measured oxygenation changes in a three-dimensional volume to allow surgeons and clinical personnel to detect and localize abnormal blood perfusion changes during or after surgery, in time for corrective intervention. The image reconstruction algorithm was validated using computerized flap models in which oxygenation was synthetically altered, whereas the optical system was preliminarily tested on a healthy forearm simulating a flap undergoing arterial and venous occlusions, proving the feasibility of implementing DOI in the form of a wearable patch for prolonged perfusion monitoring. PMID:26737630

  5. Microvascular Abnormality in Schizophrenia as Shown by Retinal Imaging

    PubMed Central

    Meier, Madeline H.; Shalev, Idan; Moffitt, Terrie E.; Kapur, Shitij; Keefe, Richard S.E.; Wong, Tien; Belsky, Daniel W.; Harrington, HonaLee; Hogan, Sean; Houts, Renate; Caspi, Avshalom; Poulton, Richie

    2013-01-01

    Objective Retinal and cerebral microvessels are structurally and functionally homologous, but, unlike cerebral microvessels, retinal microvessels can be noninvasively measured in vivo via retinal imaging. Here we test the hypothesis that individuals with schizophrenia show microvascular abnormality and evaluate the utility of retinal imaging as a tool for future schizophrenia research. Methods Participants were members of the Dunedin Study, a population-representative cohort followed from birth with 95% retention. Study members underwent retinal imaging at age 38 years. We assessed retinal arteriolar and venular caliber for all members of the cohort, including individuals who developed schizophrenia. Results Study members who developed schizophrenia were distinguished by wider retinal venules, suggesting microvascular abnormality reflective of insufficient brain oxygen supply. Analyses that controlled for confounding health conditions suggested that wider retinal venules are not simply an artifact of co-occurring health problems in schizophrenia patients. Wider venules were also associated with a dimensional measure of adult psychosis symptoms and with psychosis symptoms reported in childhood. Conclusions Findings provide initial support for the hypothesis that individuals with schizophrenia show microvascular abnormality. Moreover, results suggest that the same vascular mechanisms underlie subthreshold symptoms and clinical disorder and that these associations may begin early in life. These findings highlight the promise of retinal imaging as a tool for understanding the pathogenesis of schizophrenia. PMID:24030514

  6. Vascular effects of flavonoids.

    PubMed

    Almeida Rezende, Bruno; Pereira, Aline Carvalho; Cortes, Steyner F; Lemos, Virginia Soares

    2016-01-01

    Flavonoids are natural plant-derived polyphenolic compounds with various biological properties particularly in the cardiovascular system, including antiatherogenic, antioxidant, vasodilation, antihypertensive, and antiplatelet activities. These biological properties have been evaluated in several experimental and clinical studies. In addition, extensive reviews have discussed the antiatherogenic effect of these polyphenols. However, limited studies have investigated the potential therapeutic vascular effects of these compounds. This review brings together some recent studies, to establish the different signaling pathways involved in the molecular mechanisms that underlie the vasodilation induced by flavonoids.

  7. Medical management of vascular anomalies.

    PubMed

    Trenor, Cameron C

    2016-03-01

    We have entered an exciting era in the care of patients with vascular anomalies. These disorders require multidisciplinary care and coordination and dedicated centers have emerged to address this need. Vascular tumors have been treated with medical therapies for many years, while malformations have been historically treated with endovascular and operative procedures. The recent serendipitous discoveries of propranolol and sirolimus for vascular anomalies have revolutionized this field. In particular, sirolimus responses are challenging the dogma that vascular malformations are not biologically active. While initially explored for lymphatic anomalies, sirolimus is now being used broadly throughout the spectrum of vascular anomalies. Whether medical therapies are reserved for refractory patients or used first line is currently dependent on the experience and availability of alternative therapies at each institution. On the horizon, we anticipate new drugs targeting genes and pathways involved in vascular anomalies to be developed. Also, combinations of medications and protocols combining medical and procedural approaches are in development for refractory patients. PMID:27607327

  8. The pathobiology of vascular dementia

    PubMed Central

    Iadecola, Costantino

    2013-01-01

    Vascular cognitive impairment defines alterations in cognition, ranging from subtle deficits to full-blown dementia, attributable to cerebrovascular causes. Often coexisting with Alzheimer’s disease, mixed vascular and neurodegenerative dementia has emerged as the leading cause of age-related cognitive impairment. Central to the disease mechanism is the crucial role that cerebral blood vessels play in brain health, not only for the delivery of oxygen and nutrients, but also for the trophic signaling that links inextricably the well being of neurons and glia to that of cerebrovascular cells. This review will examine how vascular damage disrupts these vital homeostatic interactions, focusing on the hemispheric white matter, a region at heightened risk for vascular damage, and on the interplay between vascular factors and Alzheimer’s disease. Finally, preventative and therapeutic prospects will be examined, highlighting the importance of midlife vascular risk factor control in the prevention of late-life dementia. PMID:24267647

  9. Vascular trauma in civilian practice.

    PubMed Central

    Golledge, J.; Scriven, M. W.; Fligelstone, L. J.; Lane, I. F.

    1995-01-01

    Vascular trauma is associated with major morbidity and mortality, but little is known about its incidence or nature in Britain. A retrospective study of 36 patients requiring operative intervention for vascular trauma under one vascular surgeon over a 6-year period was undertaken. Twenty-four patients suffered iatrogenic trauma (median age 61 years); including cardiological intervention (19), radiological intervention (2), varicose vein surgery (1), umbilical vein catherisation (1) and isolated hyperthermic limb perfusion (1). There were 23 arterial and three venous injuries. Twelve patients had accidental trauma (median age 23 years). Three of the ten patients with blunt trauma were referred for vascular assessment before orthopaedic intervention, two after an on-table angiogram and five only after an initial orthopaedic procedure (range of delay 6 h to 10 days). Injuries were arterial in nine, venous in two and combined in one. Angiography was obtained in six patients, and in two patients with multiple upper limb fractures identified the site of injury when clinical localisation was difficult. A variety of vascular techniques were used to treat the injuries. Two patients died postoperatively and one underwent major limb amputation. Thirty-two (89%) remain free of vascular sequelae after a median follow-up of 48 months (range 3-72 months). Vascular trauma is uncommon in the United Kingdom. To repair the injuries a limited repertoire of vascular surgery techniques is needed. Therefore, vascular surgical assessment should be sought at an early stage to prevent major limb loss. PMID:8540659

  10. Pulmonary hypertension in children with congenital heart disease (PAH-CHD, PPHVD-CHD). Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK.

    PubMed

    Kozlik-Feldmann, Rainer; Hansmann, Georg; Bonnet, Damien; Schranz, Dietmar; Apitz, Christian; Michel-Behnke, Ina

    2016-05-01

    Pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) is a complex disease that presents with a broad spectrum of morphological and haemodynamic findings of varying severity. Recently, the aspect of paediatric pulmonary hypertensive vascular disease (PPHVD) has been introduced to expand the understanding of the full spectrum of pulmonary hypertension and increased pulmonary vascular resistance. Evaluation and treatment of PAH-CHD/PPHVD-CHD can be divided into in different topics. First, defining criteria for operability and initiation of advanced therapies preoperatively and postoperatively is an unresolved issue. Second, management of Eisenmenger syndrome is still an important question, with recent evidence on the severity of the disease and a more rapidly progressive course than previously described. Third, the Fontan circulation with no subpulmonary ventricle requires a distinct discussion, definition and classification since even a mild rise in pulmonary vascular resistance may lead to the so-called failing Fontan situation. Patients with CHD and single-ventricle physiology (Fontan/total cavopulmonary anastomosis) require a particularly stepwise and individualised approach. This consensus statement is on the current evidence for the most accurate evaluation and treatment of increased pulmonary artery pressure and resistance, as well as ventricular dysfunction, in children with congenital heart defects, and provides according practical recommendations. To optimise preoperative and postoperative management in patients with PAH-CHD, diagnostic and treatment algorithms are provided.

  11. Vascularization of engineered teeth.

    PubMed

    Nait Lechguer, A; Kuchler-Bopp, S; Hu, B; Haïkel, Y; Lesot, H

    2008-12-01

    The implantation of cultured dental cell-cell re-associations allows for the reproduction of fully formed teeth, crown morphogenesis, epithelial histogenesis, mineralized dentin and enamel deposition, and root-periodontium development. Since vascularization is critical for organogenesis and tissue engineering, this work aimed to study: (a) blood vessel formation during tooth development, (b) the fate of blood vessels in cultured teeth and re-associations, and (c) vascularization after in vivo implantation. Ex vivo, blood vessels developed in the dental mesenchyme from the cap to bell stages and in the enamel organ, shortly before ameloblast differentiation. In cultured teeth and re-associations, blood-vessel-like structures remained in the peridental mesenchyme, but never developed into dental tissues. After implantation, both teeth and re-associations became revascularized, although later in the case of the re-associations. In implanted re-associations, newly formed blood vessels originated from the host, allowing for their survival, and affording conditions organ growth, mineralization, and enamel secretion.

  12. Vascular Distribution of Nanomaterials

    PubMed Central

    Stapleton, Phoebe A.; Nurkiewicz, Timothy R.

    2014-01-01

    Once considered primarily occupational, novel nanotechnology innovation and application has led to widespread domestic use and intentional biomedical exposures. With these exciting advances, the breadth and depth of toxicological considerations must also be expanded. The vascular system interacts with every tissue in the body, striving to homeostasis. Engineered nanomaterials (ENM) have been reported to distribute in many different organs and tissues. However, these observations have tended to use approaches requiring tissue homogenization and/or gross organ analyses. These techniques, while effective in establishing presence, preclude an exact determination of where ENM are deposited within a tissue. It is necessary to identify this exact distribution and deposition of ENM throughout the cardiovascular system, with respect to vascular hemodynamics and in vivo/ in vitro ENM modifications taken into account if nanotechnology is to achieve its full potential. Distinct levels of the vasculature will first be described as individual compartments. Then the vasculature will be considered as a whole. These unique compartments and biophysical conditions will be discussed in terms of their propensity to favor ENM deposition. Understanding levels of the vasculature will also be discussed. Ultimately, future studies must verify the mechanisms speculated on and presented herein. PMID:24777845

  13. Vascular graft infections.

    PubMed

    Hasse, Barbara; Husmann, Lars; Zinkernagel, Annelies; Weber, Rainer; Lachat, Mario; Mayer, Dieter

    2013-01-01

    Vascular procedures are rarely complicated by infection, but if prosthetic vascular graft infection (PVGI) occurs, morbidity and mortality are high. Several patient-related, surgery-related and postoperative risk factors are reported, but they are not well validated. PVGI is due to bacterial colonisation of the wound and the underlying prosthetic graft, generally as a result of direct contamination during the operative procedure, mainly from the patient's skin or adjacent bowel. There is no consensus on diagnostic criteria or on the best management of PVGI. On the basis of reported clinical studies and our own experience, we advocate a surgical approach combining repeated radical local debridement, with graft preservation whenever possible or partial excision of the infected graft, depending on its condition, plus simultaneous negative-pressure wound therapy (NPWT). In addition, antimicrobial therapy is recommended, but there is no consensus on which classes of agent are adequate for the treatment of PVGI and whether certain infections may be treated by means of NPWT alone. Since staphylococci and Gram-negative rods are likely to be isolated, empirical treatment might include a penicillinase-resistant beta-lactam or a glycopeptide, plus an aminoglycoside, the latter for Gram-negative coverage and synergistic treatment of Gram-positive cocci. Additionally, empirical treatment might include rifampicin since it penetrates well into biofilms.

  14. 219 vascular fellows' perception of the future of vascular surgery.

    PubMed

    Hingorani, Anil P; Ascher, Enrico; Marks, Natalie; Shiferson, Alexander; Puggioni, Alessandra; Tran, Victor; Patel, Nirav; Jacob, Theresa

    2009-01-01

    In an attempt to identify the fellows' concerns about the future of the field of vascular surgery, we conducted a survey consisting of 22 questions at an annual national meeting in March from 2004 to 2007. In order to obtain accurate data, all surveys were kept anonymous. The fellows were asked (1) what type of practice they anticipated they would be in, (2) what the new training paradigm for fellows should be, (3) to assess their expectation of the needed manpower with respect to the demand for vascular surgeons, (4) what were major threats to the future of vascular surgery, (5) whether they had heard of and were in favor of the American Board of Vascular Surgery (ABVS), (6) who should be able to obtain vascular privileges, and (7) about their interest in an association for vascular surgical trainees. Of 273 attendees, 219 (80%) completed the survey. Males made up 87% of those surveyed, and 60% were between the ages of 31 and 35 years. Second-year fellows made up 82% of those surveyed. Those expecting to join a private, academic, or mixed practice made up 35%, 28%, and 20% of the respondents, respectively, with 71% anticipating entering a 100% vascular practice. Forty percent felt that 5 years of general surgery with 2 years of vascular surgery should be the training paradigm, while 45% suggested 3 and 3 years, respectively. A majority, 79%, felt that future demand would exceed the available manpower, while 17% suggested that manpower would meet demand. The major challenges to the future of vascular surgery were felt to be competition from cardiology (82%) or radiology (30%) and lack of an independent board (29%). Seventeen percent were not aware of the ABVS, and only 2% were against it; 71% suggested that vascular privileges be restricted to board-certified vascular surgeons. Seventy-six percent were interested in forming an association for vascular trainees to address the issues of the future job market (67%), endovascular training during fellowship (56

  15. Making chromosome abnormalities treatable conditions.

    PubMed

    Cody, Jannine DeMars; Hale, Daniel Esten

    2015-09-01

    Individuals affected by the classic chromosome deletion syndromes which were first identified at the beginning of the genetic age, are now positioned to benefit from genomic advances. This issue highlights five of these conditions (4p-, 5p-, 11q-, 18p-, and 18q-). It focuses on the increased in understanding of the molecular underpinnings and envisions how these can be transformed into effective treatments. While it is scientifically exciting to see the phenotypic manifestations of hemizygosity being increasingly understood at the molecular and cellular level, it is even more amazing to consider that we are now on the road to making chromosome abnormalities treatable conditions.

  16. [Erythrocyte membrane abnormalities - hereditary elliptocytosis].

    PubMed

    Kvezereli-Kopadze, M; Kvezereli-Kopadze, A; Mtvarelidze, Z; Bubuteishvili, A

    2015-04-01

    This study was designed to investigate the 4 year old boy with Hereditary Elliptocitosis (HE). The diagnosis of this rare hemolytic anemia was based on detailed family history (positive in the 4-th generation), physical examination and Para-clinical data analyses. The vast majority of patients with HE are asymptomatic, severe forms are rare. The most important is examination of blood films, which is helpful to detect the morphology abnormalities of red cells. In case of HE a different approach is required. Positive family history and series of investigations should be conducted to determine the HE.

  17. Abnormalities of the erythrocyte membrane.

    PubMed

    Gallagher, Patrick G

    2013-12-01

    Primary abnormalities of the erythrocyte membrane are characterized by clinical, laboratory, and genetic heterogeneity. Among this group, hereditary spherocytosis patients are more likely to experience symptomatic anemia. Treatment of hereditary spherocytosis with splenectomy is curative in most patients. Growing recognition of the long-term risks of splenectomy has led to re-evaluation of the role of splenectomy. Management guidelines acknowledge these considerations and recommend discussion between health care providers, patient, and family. The hereditary elliptocytosis syndromes are the most common primary disorders of erythrocyte membrane proteins. However, most elliptocytosis patients are asymptomatic and do not require therapy.

  18. Foot abnormalities of wild birds

    USGS Publications Warehouse

    Herman, C.M.; Locke, L.N.; Clark, G.M.

    1962-01-01

    The various foot abnormalities that occur in birds, including pox, scaly-leg, bumble-foot, ergotism and freezing are reviewed. In addition, our findings at the Patuxent Wildlife Research Center include pox from dove, mockingbird, cowbird, grackle and several species of sparrows. Scaly-leg has been particularly prevalent on icterids. Bumble foot has been observed in a whistling swan and in a group of captive woodcock. Ergotism is reported from a series of captive Canada geese from North Dakota. Several drug treatments recommended by others are presented.

  19. VEGF-A, cytoskeletal dynamics, and the pathological vascular phenotype

    SciTech Connect

    Nagy, Janice A. . E-mail: jnagy@bidmc.harvard.edu; Senger, Donald R. . E-mail: dsenger@bidmc.harvard.edu

    2006-03-10

    Normal angiogenesis is a complex process involving the organization of proliferating and migrating endothelial cells (ECs) into a well-ordered and highly functional vascular network. In contrast, pathological angiogenesis, which is a conspicuous feature of tumor growth, ischemic diseases, and chronic inflammation, is characterized by vessels with aberrant angioarchitecture and compromised barrier function. Herein we review the subject of pathological angiogenesis, particularly that driven by vascular endothelial growth factor (VEGF-A), from a new perspective. We propose that the serious structural and functional anomalies associated with VEGF-A-elicited neovessels, reflect, at least in part, imbalances in the internal molecular cues that govern the ordered assembly of ECs into three dimensional vascular networks and preserve vessel barrier function. Adopting such a viewpoint widens the focus from solely on specific pro-angiogenic stimuli such as VEGF-A to include a key set of cytoskeletal regulatory molecules, the Rho GTPases, which are known to direct multiple aspects of vascular morphogenesis including EC motility, alignment, multi-cellular organization, as well as intercellular junction integrity. We offer this perspective to draw attention to the importance of endothelial cytoskeletal dynamics for proper neovascularization and to suggest new therapeutic strategies with the potential to improve the pathological vascular phenotype.

  20. Cortical thickness abnormalities associated with dyslexia, independent of remediation status.

    PubMed

    Ma, Yizhou; Koyama, Maki S; Milham, Michael P; Castellanos, F Xavier; Quinn, Brian T; Pardoe, Heath; Wang, Xiuyuan; Kuzniecky, Ruben; Devinsky, Orrin; Thesen, Thomas; Blackmon, Karen

    2015-01-01

    Abnormalities in cortical structure are commonly observed in children with dyslexia in key regions of the "reading network." Whether alteration in cortical features reflects pathology inherent to dyslexia or environmental influence (e.g., impoverished reading experience) remains unclear. To address this question, we compared MRI-derived metrics of cortical thickness (CT), surface area (SA), gray matter volume (GMV), and their lateralization across three different groups of children with a historical diagnosis of dyslexia, who varied in current reading level. We compared three dyslexia subgroups with: (1) persistent reading and spelling impairment; (2) remediated reading impairment (normal reading scores), and (3) remediated reading and spelling impairments (normal reading and spelling scores); and a control group of (4) typically developing children. All groups were matched for age, gender, handedness, and IQ. We hypothesized that the dyslexia group would show cortical abnormalities in regions of the reading network relative to controls, irrespective of remediation status. Such a finding would support that cortical abnormalities are inherent to dyslexia and are not a consequence of abnormal reading experience. Results revealed increased CT of the left fusiform gyrus in the dyslexia group relative to controls. Similarly, the dyslexia group showed CT increase of the right superior temporal gyrus, extending into the planum temporale, which resulted in a rightward CT asymmetry on lateralization indices. There were no group differences in SA, GMV, or their lateralization. These findings held true regardless of remediation status. Each reading level group showed the same "double hit" of atypically increased left fusiform CT and rightward superior temporal CT asymmetry. Thus, findings provide evidence that a developmental history of dyslexia is associated with CT abnormalities, independent of remediation status.

  1. Cortical thickness abnormalities associated with dyslexia, independent of remediation status

    PubMed Central

    Ma, Yizhou; Koyama, Maki S.; Milham, Michael P.; Castellanos, F. Xavier; Quinn, Brian T.; Pardoe, Heath; Wang, Xiuyuan; Kuzniecky, Ruben; Devinsky, Orrin; Thesen, Thomas; Blackmon, Karen

    2014-01-01

    Abnormalities in cortical structure are commonly observed in children with dyslexia in key regions of the “reading network.” Whether alteration in cortical features reflects pathology inherent to dyslexia or environmental influence (e.g., impoverished reading experience) remains unclear. To address this question, we compared MRI-derived metrics of cortical thickness (CT), surface area (SA), gray matter volume (GMV), and their lateralization across three different groups of children with a historical diagnosis of dyslexia, who varied in current reading level. We compared three dyslexia subgroups with: (1) persistent reading and spelling impairment; (2) remediated reading impairment (normal reading scores), and (3) remediated reading and spelling impairments (normal reading and spelling scores); and a control group of (4) typically developing children. All groups were matched for age, gender, handedness, and IQ. We hypothesized that the dyslexia group would show cortical abnormalities in regions of the reading network relative to controls, irrespective of remediation status. Such a finding would support that cortical abnormalities are inherent to dyslexia and are not a consequence of abnormal reading experience. Results revealed increased CT of the left fusiform gyrus in the dyslexia group relative to controls. Similarly, the dyslexia group showed CT increase of the right superior temporal gyrus, extending into the planum temporale, which resulted in a rightward CT asymmetry on lateralization indices. There were no group differences in SA, GMV, or their lateralization. These findings held true regardless of remediation status. Each reading level group showed the same “double hit” of atypically increased left fusiform CT and rightward superior temporal CT asymmetry. Thus, findings provide evidence that a developmental history of dyslexia is associated with CT abnormalities, independent of remediation status. PMID:25610779

  2. A possible new role for Aβ in vascular and inflammatory dysfunction in Alzheimer's disease.

    PubMed

    Zamolodchikov, Daria; Strickland, Sidney

    2016-05-01

    Alzheimer's disease (AD) is often characterized by vascular pathology, a procoagulant state, and chronic inflammation. The mechanisms behind these abnormalities in AD are not clear. Here, we review evidence for the role of the AD-associated peptide Aβ in promoting inflammation and thrombosis in AD via its interaction with the circulating proteins factor XII and fibrinogen. PMID:27207427

  3. The metabolic vascular syndrome - guide to an individualized treatment.

    PubMed

    Hanefeld, Markolf; Pistrosch, Frank; Bornstein, Stefan R; Birkenfeld, Andreas L

    2016-03-01

    In ancient Greek medicine the concept of a distinct syndrome (going together) was used to label 'a group of signs and symptoms' that occur together and 'characterize a particular abnormality and condition'. The (dys)metabolic syndrome is a common cluster of five pre-morbid metabolic-vascular risk factors or diseases associated with increased cardiovascular morbidity, fatty liver disease and risk of cancer. The risk for major complications such as cardiovascular diseases, NASH and some cancers develops along a continuum of risk factors into clinical diseases. Therefore we still include hyperglycemia, visceral obesity, dyslipidemia and hypertension as diagnostic traits in the definition according to the term 'deadly quartet'. From the beginning elevated blood pressure and hyperglycemia were core traits of the metabolic syndrome associated with endothelial dysfunction and increased risk of cardiovascular disease. Thus metabolic and vascular abnormalities are in extricable linked. Therefore it seems reasonable to extend the term to metabolic-vascular syndrome (MVS) to signal the clinical relevance and related risk of multimorbidity. This has important implications for integrated diagnostics and therapeutic approach. According to the definition of a syndrome the rapid global rise in the prevalence of all traits and comorbidities of the MVS is mainly caused by rapid changes in life-style and sociocultural transition resp. with over- and malnutrition, low physical activity and social stress as a common soil. PMID:26956847

  4. Vascular rings: a radiological review of anatomical variations

    PubMed Central

    Ganie, Iqbal Siddi; Amod, Khatija; Reddy, Darshan

    2016-01-01

    Summary Background The imaging modalities used to diagnose vascular rings have evolved over time, from basic radiographic studies to advanced cross-sectional imaging. The goal of preoperative imaging is to provide the surgeon with an accurate representation of the ring configuration so that the surgical approach may be planned. Methods We conducted a review of all patients with vascular rings who underwent surgery at Inkosi Albert Luthuli Central Hospital, Durban, South Africa from 1 July 2008 to 1 July 2013. Results Eight patients were diagnosed with vascular rings. Seven patients had an abnormal plain chest radiograph (right aortic arch, tracheal narrowing, or abnormal mediastinal silhouette), while in six patients the contrast oesophagogram demonstrated a fixed extrinsic oesophageal indentation. Computed tomography angiography confirmed the pathology in all cases, with six double aortic arches and two right aortic arches with aberrant left subclavian artery and left ligamentum arteriosum. Conclusions We advocate a diagnostic imaging algorithm consisting of plain chest radiography, contrast oesophagogram and computed tomography angiography prior to surgery. Magnetic resonance imaging may provide an alternative axial imaging modality depending on institutional preference. PMID:26523459

  5. Medical management of abnormal pregnancy.

    PubMed

    Ratnam, S S; Prasad, R N

    1990-06-01

    Medical termination of abnormal pregnancy requires specific techniques since some conditions make therapy more effective, e.g., missed abortion intrauterine death and molar pregnancy, and others less so, e.g. anencephalic pregnancy. In all cases it is best to terminate the pregnancy as soon as possible to reduce anguish and risks of complications such as consumptive coagulopathy. Oxytocin is not consistently effective, but intraamniotic rivanol has oxytocic properties, and prostaglandins (PGs) are effective by several routes. Surgical methods are more popular in Japan and the US. A diagnostic flow chart is included and described. For missed abortion and fetal death vacuum aspiration or dilatation and evacuation are appropriate for early pregnancy, or PGs are used for later pregnancy, unless there are medical contraindications. Anencephalic pregnancy, usually diagnoses in 2nd or 3rd trimester, is resistant to medical therapy and must often be terminated by cesarean section. Molar pregnancy can be managed with vacuum aspiration at any length of gestation, but must be completed by curettage. Intraamniotic PGs are not advised for mole or fetal death. PG analogs can be administered intramuscularly, or vaginally in gel form. Other types of abnormal pregnancy that can be managed with PGs are spina bifida, hydrocephalus, hydrops fetalis, Dandy-Walker syndrome and Down's syndrome. Tubal pregnancy can be evacuated with intratubally administered PGs under laparoscopic control, thereby preserving tubal integrity. PMID:2225605

  6. Flow effects of blood constitutive equations in 3D models of vascular anomalies

    NASA Astrophysics Data System (ADS)

    Neofytou, Panagiotis; Tsangaris, Sokrates

    2006-06-01

    The effects of different blood rheological models are investigated numerically utilizing two three- dimensional (3D) models of vascular anomalies, namely a stenosis and an abdominal aortic aneurysm model. The employed CFD code incorporates the SIMPLE scheme in conjunction with the finite-volume method with collocated arrangement of variables. The approximation of the convection terms is carried out using the QUICK differencing scheme, whereas the code enables also multi-block computations, which are useful in order to cope with the two-block grid structure of the current computational domain. Three non-Newtonian models are employed, namely the Casson, Power-Law and Quemada models, which have been introduced in the past for modelling the rheological behaviour of blood and cover both the viscous as well as the two-phase character of blood. In view of the haemodynamical mechanisms related to abnormalities in the vascular network and the role of the wall shear stress in initiating and further developing of arterial diseases, the present study focuses on the 3D flow field and in particular on the distribution as well as on both low and high values of the wall shear stress in the vicinity of the anomaly. Finally, a comparison is made between the effects of each rheological model on the aforementioned parameters. Results show marked differences between simulating blood as Newtonian and non-Newtonian fluid and furthermore the Power-Law model exhibits different behaviour in all cases compared to the other models whereas Quemada and Casson models exhibit similar behaviour in the case of the stenosis but different behaviour in the case of the aneurysm.

  7. Abnormal Spinal Cord Magnetic Resonance Signal: Approach to the Differential Diagnosis.

    PubMed

    Morales, Humberto; Betts, Aaron

    2016-10-01

    T2-hyperintense signal abnormalities within the spinal cord on magnetic resonance imaging can evoke a broad differential diagnosis and can present a diagnostic dilemma. Here, we review and provide a succinct and relevant differential diagnosis based on imaging patterns and anatomical or physiopathologic correlation. Clues and imaging pearls are provided focusing on inflammatory, infectious, demyelinating, vascular, and metabolic involvement of the spinal cord. PMID:27616311

  8. Ultrasensitive detection of 3D cerebral microvascular network dynamics in vivo

    PubMed Central

    Pan, Yingtian; You, Jiang; Volkow, Nora D.; Park, Ki; Du, Congwu

    2014-01-01

    Despite widespread applications of multiphoton microscopy in microcirculation, its small field of view and inability to instantaneously quantify cerebral blood flow velocity (CBFv) in vascular networks limit its utility in investigating the heterogeneous responses to brain stimulations. Optical Doppler tomography (ODT) provides 3D images of CBFv networks, but it suffers poor sensitivity for measuring capillary flows. Here we report a new method, contrast-enhanced ODT with intralipid that significantly improves quantitative CBFv imaging of capillary networks by obviating the errors from long latency between flowing red blood cells (low hematocrit ~20% in capillaries). This enhanced sensitivity allowed us to measure the ultraslow microcirculation surrounding a brain tumor and the abnormal ingrowth of capillary flows in the tumor as well as in ischemia triggered by chronic cocaine in the mouse brain that could not be detected by regular ODT. It also enabled significantly enhanced sensitivity for quantifying the heterogeneous CBFv responses of vascular networks to acute cocaine. Inasmuch as intralipids are widely used for parenteral nutrition the intralipid contrast method has translational potential for clinical applications. PMID:25192654

  9. Aberrant Functional Connectivity and Structural Atrophy in Subcortical Vascular Cognitive Impairment: Relationship with Cognitive Impairments.

    PubMed

    Zhou, Xia; Hu, Xiaopeng; Zhang, Chao; Wang, Haibao; Zhu, Xiaoqun; Xu, Liyan; Sun, Zhongwu; Yu, Yongqiang

    2016-01-01

    Abnormal structures in the cortical and subcortical regions have been identified in subcortical vascular cognition impairment (SVCI). However, little is known about the functional alterations in SVCI, and no study refers to the functional connectivity in the prefrontal and subcortical regions in this context. The medial prefrontal cortex (MPFC) is an important region of the executive network and default mode network, and the subcortical thalamus plays vital roles in mediating or modulating these two networks. To investigate both thalamus- and MPFC-related functional connectivity as well as its relationship with cognition in SVCI, 32 SVCI patients and 23 control individuals were administered neuropsychological assessments. They also underwent structural and functional magnetic resonance imaging scans. Voxel-based morphometry and functional connectivity analysis were performed to detect gray matter (GM) atrophy and to characterize the functional alterations in the thalamus and the MPFC. For structural data, we observed that GM atrophy was distributed in both cortical regions and subcortical areas. For functional data, we observed that the thalamus functional connectivity in SVCI was significantly decreased in several cortical regions [i.e., the orbitofrontal lobe (OFL)], which are mainly involved in executive function and memory function. However, connectivity was increased in several frontal regions (i.e., the inferior frontal gyrus), which may be induced by the compensatory recruitment of the decreased functional connectivity. The MPFC functional connectivity was also decreased in executive- and memory-related regions (i.e., the anterior cingulate cortex) along with a motor region (i.e., the supplementary motor area). In addition, the cognitive performance was closely correlated with functional connectivity between the left thalamus and the left OFL in SVCI. The present study, thus, provides evidence for an association between structural and functional alterations

  10. Aberrant Functional Connectivity and Structural Atrophy in Subcortical Vascular Cognitive Impairment: Relationship with Cognitive Impairments

    PubMed Central

    Zhou, Xia; Hu, Xiaopeng; Zhang, Chao; Wang, Haibao; Zhu, Xiaoqun; Xu, Liyan; Sun, Zhongwu; Yu, Yongqiang

    2016-01-01

    Abnormal structures in the cortical and subcortical regions have been identified in subcortical vascular cognition impairment (SVCI). However, little is known about the functional alterations in SVCI, and no study refers to the functional connectivity in the prefrontal and subcortical regions in this context. The medial prefrontal cortex (MPFC) is an important region of the executive network and default mode network, and the subcortical thalamus plays vital roles in mediating or modulating these two networks. To investigate both thalamus- and MPFC-related functional connectivity as well as its relationship with cognition in SVCI, 32 SVCI patients and 23 control individuals were administered neuropsychological assessments. They also underwent structural and functional magnetic resonance imaging scans. Voxel-based morphometry and functional connectivity analysis were performed to detect gray matter (GM) atrophy and to characterize the functional alterations in the thalamus and the MPFC. For structural data, we observed that GM atrophy was distributed in both cortical regions and subcortical areas. For functional data, we observed that the thalamus functional connectivity in SVCI was significantly decreased in several cortical regions [i.e., the orbitofrontal lobe (OFL)], which are mainly involved in executive function and memory function. However, connectivity was increased in several frontal regions (i.e., the inferior frontal gyrus), which may be induced by the compensatory recruitment of the decreased functional connectivity. The MPFC functional connectivity was also decreased in executive- and memory-related regions (i.e., the anterior cingulate cortex) along with a motor region (i.e., the supplementary motor area). In addition, the cognitive performance was closely correlated with functional connectivity between the left thalamus and the left OFL in SVCI. The present study, thus, provides evidence for an association between structural and functional alterations

  11. Aberrant Functional Connectivity and Structural Atrophy in Subcortical Vascular Cognitive Impairment: Relationship with Cognitive Impairments.

    PubMed

    Zhou, Xia; Hu, Xiaopeng; Zhang, Chao; Wang, Haibao; Zhu, Xiaoqun; Xu, Liyan; Sun, Zhongwu; Yu, Yongqiang

    2016-01-01

    Abnormal structures in the cortical and subcortical regions have been identified in subcortical vascular cognition impairment (SVCI). However, little is known about the functional alterations in SVCI, and no study refers to the functional connectivity in the prefrontal and subcortical regions in this context. The medial prefrontal cortex (MPFC) is an important region of the executive network and default mode network, and the subcortical thalamus plays vital roles in mediating or modulating these two networks. To investigate both thalamus- and MPFC-related functional connectivity as well as its relationship with cognition in SVCI, 32 SVCI patients and 23 control individuals were administered neuropsychological assessments. They also underwent structural and functional magnetic resonance imaging scans. Voxel-based morphometry and functional connectivity analysis were performed to detect gray matter (GM) atrophy and to characterize the functional alterations in the thalamus and the MPFC. For structural data, we observed that GM atrophy was distributed in both cortical regions and subcortical areas. For functional data, we observed that the thalamus functional connectivity in SVCI was significantly decreased in several cortical regions [i.e., the orbitofrontal lobe (OFL)], which are mainly involved in executive function and memory function. However, connectivity was increased in several frontal regions (i.e., the inferior frontal gyrus), which may be induced by the compensatory recruitment of the decreased functional connectivity. The MPFC functional connectivity was also decreased in executive- and memory-related regions (i.e., the anterior cingulate cortex) along with a motor region (i.e., the supplementary motor area). In addition, the cognitive performance was closely correlated with functional connectivity between the left thalamus and the left OFL in SVCI. The present study, thus, provides evidence for an association between structural and functional alterations

  12. Vascular surgery: the European perspective.

    PubMed

    Harris, P

    1999-09-01

    Isaac Newton, among others, observed that 'we see so far because we are standing upon the shoulders of giants'. In vascular surgery most of the giants have been European, and this is a heritage which we as Europeans can take pride in and build upon if we chose to do so. As in other areas of life, commitment is essential in order to influence the future. For vascular surgeons in Europe this means active participation in the European scientific societies for vascular surgery and in the UEMS. The main value of the EBSQ.VASC assessments to date has been to expose the uneven standards of training in vascular surgery within the European Union. Only if action follows to address these inequalities will the tactics of the European Board of Vascular Surgery be vindicated.

  13. Caffeine's Vascular Mechanisms of Action

    PubMed Central

    Echeverri, Darío; Montes, Félix R.; Cabrera, Mariana; Galán, Angélica; Prieto, Angélica

    2010-01-01

    Caffeine is the most widely consumed stimulating substance in the world. It is found in coffee, tea, soft drinks, chocolate, and many medications. Caffeine is a xanthine with various effects and mechanisms of action in vascular tissue. In endothelial cells, it increases intracellular calcium stimulating the production of nitric oxide through the expression of the endothelial nitric oxide synthase enzyme. Nitric oxide is diffused to the vascular smooth muscle cell to produce vasodilation. In vascular smooth muscle cells its effect is predominantly a competitive inhibition of phosphodiesterase, producing an accumulation of cAMP and vasodilation. In addition, it blocks the adenosine receptors present in the vascular tissue to produce vasoconstriction. In this paper the main mechanisms of action of caffeine on the vascular tissue are described, in which it is shown that caffeine has some cardiovascular properties and effects which could be considered beneficial. PMID:21188209

  14. Pulmonary vascular disease in mice xenografted with human BM progenitors from patients with pulmonary arterial hypertension

    PubMed Central

    Farha, Samar; Lichtin, Alan; Graham, Brian; George, Deepa; Aldred, Micheala; Hazen, Stanley L.; Loyd, James; Tuder, Rubin

    2012-01-01

    Hematopoietic myeloid progenitors released into the circulation are able to promote vascular remodeling through endothelium activation and injury. Endothelial injury is central to the development of pulmonary arterial hypertension (PAH), a proliferative vasculopathy of the pulmonary circulation, but the origin of vascular injury is unknown. In the present study, mice transplanted with BM-derived CD133+ progenitor cells from patients with PAH, but not from healthy controls, exhibited morbidity and/or death due to features of PAH: in situ thrombi and endothelial injury, angioproliferative remodeling, and right ventricular hypertrophy and failure. Myeloid progenitors from patients with heritable and/or idiopathic PAH all produced disease in xenografted mice. Analyses of hematopoietic transcription factors and colony formation revealed underlying abnormalities of progenitors that skewed differentiation toward the myeloid-erythroid lineage. The results of the present study suggest a causal role for hematopoietic stem cell abnormalities in vascular injury, right ventricular hypertrophy, and morbidity associated with PAH. PMID:22745307

  15. Phase transitions in tumor growth: III vascular and metastasis behavior

    NASA Astrophysics Data System (ADS)

    Llanos-Pérez, J. A.; Betancourt-Mar, J. A.; Cocho, G.; Mansilla, R.; Nieto-Villar, José Manuel

    2016-11-01

    We propose a mechanism for avascular, vascular and metastasis tumor growth based on a chemical network model. Vascular growth and metastasis, appear as a hard phase transition type, as "first order", through a supercritical Andronov-Hopf bifurcation, emergence of limit cycle and then through a cascade of bifurcations type saddle-foci Shilnikov's bifurcation. Finally, the thermodynamics framework developed shows that the entropy production rate, as a Lyapunov function, indicates the directional character and stability of the dynamical behavior of tumor growth according to this model.

  16. Abnormal fronto-striatal functional connectivity in Parkinson's disease.

    PubMed

    Xu, Jinping; Zhang, Jiuquan; Wang, Jiaojian; Li, Guanglin; Hu, Qingmao; Zhang, Yuanchao

    2016-02-01

    Parkinson's disease (PD) is characterized by the relatively selective depletion of dopamine in the striatum, which consequently leads to dysfunctions in cortico-striatal-thalamic-cortical circuitries. It has been shown that the most common cognitive deficits in PD patients are related to the fronto-striatal circuits. In PD, most previous functional connectivity studies have been performed using seed-based methods to identify the brain regions that are abnormally connected to one or more seeds, but these cannot be used to quantify the interactions between one region and all other regions in a particular network. Functional connectivity degree, which is a measurement that can be used to quantify the functional or structural connectivity of a complex brain network, was adopted in this study to assess the interactions of the fronto-striatal network. Compared to healthy controls, PD patients had significantly decreased total functional connectivity degree for the left putamen and the right globus pallidum in fronto-striatal networks. Additionally, negative correlations between the fronto-pallial functional connectivity degree (i.e., the right globus pallidum with the left middle frontal gyrus, and with the right triangular part of inferior frontal gyrus) and disease duration were observed in PD patients. The results of this study demonstrate that fronto-striatal functional connectivity is abnormal in patients with PD and indicate that these deficits might be the result of motor and cognitive dysfunctions in PD patients. PMID:26724369

  17. Mechanisms of Vascular Calcification: The Pivotal Role of Pyruvate Dehydrogenase Kinase 4

    PubMed Central

    2016-01-01

    Vascular calcification, abnormal mineralization of the vessel wall, is frequently associated with aging, atherosclerosis, diabetes mellitus, and chronic kidney disease. Vascular calcification is a key risk factor for many adverse clinical outcomes, including ischemic cardiac events and subsequent cardiovascular mortality. Vascular calcification was long considered to be a passive degenerative process, but it is now recognized as an active and highly regulated process similar to bone formation. However, despite numerous studies on the pathogenesis of vascular calcification, the mechanisms driving this process remain poorly understood. Pyruvate dehydrogenase kinases (PDKs) play an important role in the regulation of cellular metabolism and mitochondrial function. Recent studies show that PDK4 is an attractive therapeutic target for the treatment of various metabolic diseases. In this review, we summarize our current knowledge regarding the mechanisms of vascular calcification and describe the role of PDK4 in the osteogenic differentiation of vascular smooth muscle cells and development of vascular calcification. Further studies aimed at understanding the molecular mechanisms of vascular calcification will be critical for the development of novel therapeutic strategies. PMID:26996423

  18. Automatic Semantic Priming Abnormalities in Schizophrenia

    PubMed Central

    Mathalon, Daniel H.; Roach, Brian J.; Ford, Judith M.

    2014-01-01

    Abnormal activation of semantic networks characterizes schizophrenia and can be studied using the N400 event-related potential (ERP). N400 is elicited by words that are not primed by the preceding context and provides a direct measure of the neural mechanisms underlying semantic priming. Semantic priming refers to facilitated semantic processing gained through pre-exposure to semantic context, which can happen automatically if the interval between the prime and target is very short. We predicted that (1) schizophrenia patients have overly inclusive semantic networks, reflected in a less negative than expected N400 to relatively unprimed words, and (2) schizophrenia patients are deficient in their use of semantic context, responding to primed words as if they were unprimed, reflected in a more negative than expected N400 to primed words. N400s were acquired from patients with DSM-IV schizophrenia (n=26) and age-matched healthy comparison subjects (n=29) performing a picture-word verification (match vs. non-match) task. Word targets were presented 325ms after a picture prime, which either matched (CAMEL→”camel”), or did not match (In Category: CAMEL→”cow; Out Category: CAMEL→”candle”) the prime. N400 data suggest that both patients and controls are sensitive to the difference between primed and unprimed words, but patients are less sensitive than controls. Similarly, N400 data suggest that both groups were sensitive to the subtler difference between classes of unprimed words (In Category versus Out Category picture-word non-matches), but patients are less sensitive, especially those with prominent negative symptoms. PMID:19995582

  19. In Vivo Angiography Quantifies Oxygen-Induced Retinopathy Vascular Recovery

    PubMed Central

    Mezu-Ndubuisi, Olachi J.

    2016-01-01

    ABSTRACT Purpose Retinopathy of prematurity (ROP) is a potentially blinding vasoproliferative disease. There is no standardized way to quantify plus disease (tortuous and dilated retinal vessels) or characterize abnormal recovery during ROP monitoring. This study objectively studies vascular features in live mice during development using noninvasive retinal imaging. Methods Using fluorescein angiography (FA), retinal vascular features were quantified in live mice with oxygen induced retinopathy (OIR). A total of 105 wild-type mice were exposed to 77% oxygen from postnatal day 7 (P7) till P12 (OIR mice). Also, 105 age-matched pups were raised in room air (RA mice). In vivo FA was performed at early (P16 to P20), mid (P23 to P27), late (P30 to P34), and mature (P47) phases of retinal vascular development. Retinal vascular area, retinal vein width, and retinal artery tortuosity were quantified. Results Retinal artery tortuosity was higher in OIR than RA mice at early (p < 0.0001), mid (p < 0.0001), late (p < 0.0001), and mature (p < 0.0001) phases. Retinal vascular area in OIR mice increased from early to mid-phase (p < 0.0001), but remained unchanged from mid to late (p = 0.23), and from late to mature phase (p = 0.98). Retinal vein width was larger in OIR mice compared to RA mice during early phase only. Arteries in OIR mice were more tortuous from early to mid-phase (p < 0.0001), but tortuosity remained stable from mid through mature phase. RA mice had an increase in retinal vascular area from early to late phase, but maintained uniform retinal vein width and retinal artery tortuosity in all phases. Conclusions In vivo FA distinguished arterial and venous features, similar to plus disease, and revealed aberrant recovery of OIR mice (arterial tortuosity, reduced capillary density, and absent neovascular buds) that persisted into adulthood. Retinal artery tortuosity may be a reliable, objective marker of severity of ROP. Infants with abnormal retinal vascular

  20. Transient global amnesia: hippocampal magnetic resonance imaging abnormalities.

    PubMed

    Alberici, Elisa; Pichiecchio, Anna; Caverzasi, Eduardo; Farina, Lisa Maria; Persico, Alessandra; Cavallini, Anna; Bastianello, Stefano

    2008-01-01

    Transient global amnesia (TGA) is an episodic dysfunction of declarative memory that usually resolves within 12 hours and whose underlying pathophysiological mechanisms are still unclear. Recent studies, on the basis of transient focal high-signal abnormalities in the hippocampus on diffusion-weighted imaging (DWI), suggest involvement of memory circuits in the temporo-mesial region. Out of a total of 65 patients presenting with acute or subacute TGA between May 2004 and May 2008, we retrospectively analysed 21 in whom a DWI sequence was performed. Five patients showed a focal hippocampal signal alteration both on DWI and on conventional T2; this alteration was no longer detectable on follow-up MRI two months later. The presence of transient DWI and T2 alterations in the hippocampal formation suggests that TGA could have a multifactorial, non-vascular aetiology. The presence of local susceptibility to neuronal metabolic stress emerges as a likely hypothesis.

  1. Vascular toxicity of silver nanoparticles to developing zebrafish (Danio rerio).

    PubMed

    Gao, Jiejun; Mahapatra, Cecon T; Mapes, Christopher D; Khlebnikova, Maria; Wei, Alexander; Sepúlveda, Marisol S

    2016-11-01

    Nanoparticles (NPs, 1-100 nm) can enter the environment and result in exposure to humans and other organisms leading to potential adverse health effects. The aim of the present study is to evaluate the effects of early life exposure to polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs, 50 nm), particularly with respect to vascular toxicity on zebrafish embryos and larvae (Danio rerio). Previously published data has suggested that PVP-AgNP exposure can inhibit the expression of genes within the vascular endothelial growth factor (VEGF) signaling pathway, leading to delayed and abnormal vascular development. Here, we show that early acute exposure (0-12 h post-fertilization, hpf) of embryos to PVP-AgNPs at 1 mg/L or higher results in a transient, dose-dependent induction in VEGF-related gene expression that returns to baseline levels at hatching (72 hpf). Hatching results in normoxia, negating the effects of AgNPs on vascular development. Interestingly, increased gene transcription was not followed by the production of associated proteins within the VEGF pathway, which we attribute to NP-induced stress in the endoplasmic reticulum (ER). The impaired translation may be responsible for the observed delays in vascular development at later stages, and for smaller larvae size at hatching. Silver ion (Ag(+)) concentrations were < 0.001 mg/L at all times, with no significant effects on the VEGF pathway. We propose that PVP-AgNPs temporarily delay embryonic vascular development by interfering with oxygen diffusion into the egg, leading to hypoxic conditions and ER stress.

  2. Vascular toxicity of silver nanoparticles to developing zebrafish (Danio rerio).

    PubMed

    Gao, Jiejun; Mahapatra, Cecon T; Mapes, Christopher D; Khlebnikova, Maria; Wei, Alexander; Sepúlveda, Marisol S

    2016-11-01

    Nanoparticles (NPs, 1-100 nm) can enter the environment and result in exposure to humans and other organisms leading to potential adverse health effects. The aim of the present study is to evaluate the effects of early life exposure to polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs, 50 nm), particularly with respect to vascular toxicity on zebrafish embryos and larvae (Danio rerio). Previously published data has suggested that PVP-AgNP exposure can inhibit the expression of genes within the vascular endothelial growth factor (VEGF) signaling pathway, leading to delayed and abnormal vascular development. Here, we show that early acute exposure (0-12 h post-fertilization, hpf) of embryos to PVP-AgNPs at 1 mg/L or higher results in a transient, dose-dependent induction in VEGF-related gene expression that returns to baseline levels at hatching (72 hpf). Hatching results in normoxia, negating the effects of AgNPs on vascular development. Interestingly, increased gene transcription was not followed by the production of associated proteins within the VEGF pathway, which we attribute to NP-induced stress in the endoplasmic reticulum (ER). The impaired translation may be responsible for the observed delays in vascular development at later stages, and for smaller larvae size at hatching. Silver ion (Ag(+)) concentrations were < 0.001 mg/L at all times, with no significant effects on the VEGF pathway. We propose that PVP-AgNPs temporarily delay embryonic vascular development by interfering with oxygen diffusion into the egg, leading to hypoxic conditions and ER stress. PMID:27499207

  3. Angiogenesis in tissue engineering: from concept to the vascularization of scaffold construct

    NASA Astrophysics Data System (ADS)

    Amirah Ishak, Siti; Pangestu Djuansjah, J. R.; Kadir, M. R. Abdul; Sukmana, Irza

    2014-06-01

    Angiogenesis, the formation of micro-vascular network from the preexisting vascular vessels, has been studied in the connection to the normal developmental process as well as numerous diseases. In tissue engineering research, angiogenesis is also essential to promote micro-vascular network inside engineered tissue constructs, mimicking a functional blood vessel in vivo. Micro-vascular network can be used to maintain adequate tissue oxygenation, nutrient transfer and waste removal. One of the problems faced by angiogenesis researchers is to find suitable in vitro assays and methods for assessing the effect of regulators on angiogenesis and micro-vessel formation. The assay would be reliable and repeatable with easily quantifiable with physiologically relevant. This review aims to highlights recent advanced and future challenges in developing and using an in vitro angiogenesis assay for the application on biomedical and tissue engineering research.

  4. Physiological consequences of abnormal connectivity in a developmental epilepsy

    PubMed Central

    Shafi, Mouhsin M.; Vernet, Marine; Klooster, Debby; Chu, Catherine J.; Boric, Katica; Barnard, Mollie E.; Romatoski, Kelsey; Westover, M. Brandon; Christodoulou, Joanna A.; Gabrieli, John D.E.; Whitfield-Gabrieli, Susan; Pascual-Leone, Alvaro; Chang, Bernard S.

    2015-01-01

    Objective Many forms of epilepsy are associated with aberrant neuronal connections, but the relationship between such pathological connectivity and the underlying physiological predisposition to seizures is unclear. We sought to characterize the cortical excitability profile of a developmental form of epilepsy known to have structural and functional connectivity abnormalities. Methods We employed transcranial magnetic stimulation (TMS) with simultaneous EEG recording in eight patients with epilepsy from periventricular nodular heterotopia (PNH) and matched healthy controls. We used connectivity imaging findings to guide TMS targeting and compared the evoked responses to single-pulse stimulation from different cortical regions. Results Heterotopia patients with active epilepsy demonstrated a relatively augmented late cortical response that was greater than that of matched controls. This abnormality was specific to cortical regions with connectivity to subcortical heterotopic gray matter. Topographic mapping of the late response differences showed distributed cortical networks that were not limited to the stimulation site, and source analysis in one subject revealed that the generator of abnormal TMS-evoked activity overlapped with the spike and seizure onset zone. Interpretation Our findings indicate that patients with epilepsy from gray matter heterotopia have altered cortical physiology consistent with hyperexcitability, and that this abnormality is specifically linked to the presence of aberrant connectivity. These results support the idea that TMS-EEG could be a useful biomarker in epilepsy in gray matter heterotopia, expand our understanding of circuit mechanisms of epileptogenesis, and have potential implications for therapeutic neuromodulation in similar epileptic conditions associated with deep lesions. PMID:25858773

  5. Adults with Chromosome 18 Abnormalities.

    PubMed

    Soileau, Bridgette; Hasi, Minire; Sebold, Courtney; Hill, Annice; O'Donnell, Louise; Hale, Daniel E; Cody, Jannine D

    2015-08-01

    The identification of an underlying chromosome abnormality frequently marks the endpoint of a diagnostic odyssey. However, families are frequently left with more questions than answers as they consider their child's future. In the case of rare chromosome conditions, a lack of longitudinal data often makes it difficult to provide anticipatory guidance to these families. The objective of this study is to describe the lifespan, educational attainment, living situation, and behavioral phenotype of adults with chromosome 18 abnormalities. The Chromosome 18 Clinical Research Center has enrolled 483 individuals with one of the following conditions: 18q-, 18p-, Tetrasomy 18p, and Ring 18. As a part of the ongoing longitudinal study, we collect data on living arrangements, educational level attained, and employment status as well as data on executive functioning and behavioral skills on an annual basis. Within our cohort, 28 of the 483 participants have died, the majority of whom have deletions encompassing the TCF4 gene or who have unbalanced rearrangement involving other chromosomes. Data regarding the cause of and age at death are presented. We also report on the living situation, educational attainment, and behavioral phenotype of the 151 participants over the age of 18. In general, educational level is higher for people with all these conditions than implied by the early literature, including some that received post-high school education. In addition, some individuals are able to live independently, though at this point they represent a minority of patients. Data on executive function and behavioral phenotype are also presented. Taken together, these data provide insight into the long-term outcome for individuals with a chromosome 18 condition. This information is critical in counseling families on the range of potential outcomes for their child.

  6. βA3/A1-crystallin is required for proper astrocyte template formation and vascular remodeling in the retina

    PubMed Central

    Sinha, Debasish; Valapala, Mallika; Bhutto, Imran; Patek, Bonnie; Zhang, Cheng; Hose, Stacey; Yang, Fang; Cano, Marisol; Stark, Walter J.; Lutty, Gerard A.; Zigler, J. Samuel; Wawrousek, Eric F.

    2013-01-01

    Nuc1 is a spontaneous rat mutant resulting from a mutation in the Cryba1 gene, coding for βA3/A1-crystallin. Our earlier studies with Nuc1 provided novel evidence that astrocytes, which express βA3/A1-crystallin, have a pivotal role in retinal remodeling. The role of astrocytes in the retina is only beginning to be explored. One of the limitations in the field is the lack of appropriate animal models to better investigate the function of astrocytes in retinal health and disease. We have now established transgenic mice that overexpress the Nuc1 mutant form of Cryba1, specifically in astrocytes. Astrocytes in wild type mice show normal compact stellate structure, producing a honeycomb-like network. In contrast, in transgenics over-expressing the mutant (Nuc1) Cryba1 in astrocytes, bundle-like structures with abnormal patterns and morphology were observed. In the nerve fiber layer of the transgenic mice, an additional layer of astrocytes adjacent to the vitreous is evident. This abnormal organization of astrocytes affects both the superficial and deep retinal vascular density and remodeling. Fluorescein angiography showed increased venous dilation and tortuosity of branches in the transgenic retina, as compared to wild type. Moreover, there appear to be fewer interactions between astrocytes and endothelial cells in the transgenic retina than in normal mouse retina. Further, astrocytes overexpressing the mutant βA3/A1-crystallin migrate into the vitreous, and ensheath the hyaloid artery, in a manner similar to that seen in the Nuc1 rat. Together, these data demonstrate that developmental abnormalities of astrocytes can affect the normal remodeling process of both fetal and retinal vessels of the eye and that βA3/A1-crystallin is essential for normal astrocyte function in the retina. PMID:22427112

  7. [Updates from the 45th Congress of French College for Vascular Disease (CFPV) Paris, March the 16th-18th, 2011].

    PubMed

    Lazareth, I; Priollet, P

    2011-12-01

    The 45(th) Congress of the French College of Vascular Disease (CFPV) has been held in Paris in March 2011. Scientific sessions covered many fields of vascular diseases. A short synthesis is proposed there. A large part of the programme is related to new treatments for venous thrombo-embolic disease, healing factors of chronic leg ulcers, medical networks, hormones and atherothrombosis, cardiovascular risk in connective tissue diseases, vascular treatment and elderly, vascular compression syndromes, nailfold capillary microscopy.

  8. Diffuse and uncontrolled vascular smooth muscle cell proliferation in rapidly progressing pediatric moyamoya disease.

    PubMed

    Reid, Amy J; Bhattacharjee, Meenakshi B; Regalado, Ellen S; Milewicz, Allen L; El-Hakam, Lisa M; Dauser, Robert C; Milewicz, Dianna M

    2010-09-01

    Moyamoya disease is a rare stroke syndrome of unknown etiology resulting from stenosis or occlusion of the supraclinoid internal carotid artery (ICA) in association with an abnormal vascular network in the basal ganglia. Although the highest incidence of moyamoya disease is in pediatric patients, pathology reports have been primarily limited to adult samples and describe occlusive fibrocellular lesions in the intimae of affected arteries. We describe the case of a young girl with primary moyamoya disease who presented at 18 months of age with right hemiparesis following an ischemic stroke. Angiography showed stenosis of the distal left ICA, left middle cerebral artery, and right ICA. An emergent left-sided dural inversion was performed. Recurrent strokes and alternating hemiplegia necessitated a right dural inversion 6 months later. Nonetheless, her aggressive disease proved uniquely refractory to surgical revascularization, and she succumbed to recurrent strokes and neurological deterioration at 2.5 years of age. Pathological specimens revealed a striking bilateral occlusion of the anterior carotid circulation resulting from intimal proliferation of smooth muscle cells (SMCs). Most strikingly, the ascending aorta and the superior mesenteric artery demonstrated similar intimal proliferation, along with SMC proliferation in the media. The systemic pathology involving multiple arteries in this extremely young child, the first case of its kind available for autopsy, suggests that globally uncontrolled SMC proliferation, in the absence of environmental risk factors and likely resulting from an underlying genetic alteration, may be a primary etiologic event leading to moyamoya disease. PMID:20809708

  9. Resveratrol improves high-fructose-induced vascular dysfunction in rats.

    PubMed

    Develi-Is, Seval; Ozen, Gulsev; Bekpinar, Seldag; Topal, Gokce; Unlucerci, Yesim; Dogan, B Sonmez Uydes; Uysal, Mujdat

    2014-12-01

    High levels of fructose in the diet results in metabolic abnormalities and vascular disorders. In this study, the effect of resveratrol (RES) on vascular relaxation and contraction responses was examined in the aorta of high-fructose (HFr)-fed rats. mRNA expressions of aortic sirtuin 1 (SIRT1), GLUT5, and aldolase B were also investigated. Rats were given fructose (30%) and (or) RES (50 mg · L(-1)) in their drinking water for 8 weeks. In the HFr-fed rats, plasma levels of arginine and the ratio of arginine:asymmetric dimethylarginine (ADMA) decreased, whereas leptin levels increased. Decreased relaxation and increased contractile responses were detected in aortic rings. However, the aortic expressions of SIRT1, GLUT5, and aldolase B remained unchanged. RES treatment restored HFr-induced vascular dysfunction without improvements in insulin resistance. Treatment of HFr-fed rats with RES increased plasma levels of arginine and the L-arginine:ADMA ratio, and decreased plasma levels of leptin. RES increased SIRT1 expression, but decreased the expression of GLUT5 and aldolase B in aortas from HFr-fed rats. These results suggest that RES contributes to the restoration of HFr-induced vascular dysfunction in rats, at least in part, by up-regulation of SIRT 1 and down-regulation of GLUT5 and aldolase B in the aorta. Moreover, RES may have a positive influence on vasculature by partly restoring the plasma arginine:ADMA ratio and leptin levels.

  10. Aberrant Pulmonary Vascular Growth and Remodeling in Bronchopulmonary Dysplasia

    PubMed Central

    Alvira, Cristina M.

    2016-01-01

    In contrast to many other organs, a significant portion of lung development occurs after birth during alveolarization, thus rendering the lung highly susceptible to injuries that may disrupt this developmental process. Premature birth heightens this susceptibility, with many premature infants developing the chronic lung disease, bronchopulmonary dysplasia (BPD), a disease characterized by arrested alveolarization. Over the past decade, tremendous progress has been made in the elucidation of mechanisms that promote postnatal lung development, including extensive data suggesting that impaired pulmonary angiogenesis contributes to the pathogenesis of BPD. Moreover, in addition to impaired vascular growth, patients with BPD also frequently demonstrate alterations in pulmonary vascular remodeling and tone, increasing the risk for persistent hypoxemia and the development of pulmonary hypertension. In this review, an overview of normal lung development will be presented, and the pathologic features of arrested development observed in BPD will be described, with a specific emphasis on the pulmonary vascular abnormalities. Key pathways that promote normal pulmonary vascular development will be reviewed, and the experimental and clinical evidence demonstrating alterations of these essential pathways in BPD summarized. PMID:27243014

  11. The role of the vascular endothelium in arenavirus haemorrhagic fevers.

    PubMed

    Kunz, Stefan

    2009-12-01

    Viral haemorrhagic fevers (VHF) caused by arenaviruses are among the most devastating emerging human diseases. The most important pathogen among the arenaviruses is Lassa virus (LASV), the causative agent of Lassa fever that is endemic to West Africa. On the South American continent, the New World arenavirus Junin virus (JUNV), Machupo (MACV), Guanarito (GTOV), and Sabia virus (SABV) have emerged as causative agents of severe VHFs. Clinical and experimental studies on arenavirus VHF have revealed a crucial role of the endothelium in their pathogenesis. However, in contrast to other VHFs, haemorrhages are not a salient feature of Lassa fever and fatal cases do not show overt destruction of vascular tissue. The functional alteration of the vascular endothelium that precede shock and death in fatal Lassa fever may be due to more subtle direct or indirect effects of the virus on endothelial cells. Haemorrhagic disease manifestations and vascular involvement are more pronounced in the VHF caused by the South American haemorrhagic fever viruses. Recent studies on JUNV revealed perturbation of specific endothelial cell function, including expression of cell adhesion molecules, coagulation factors, and vasoactive mediators as a consequence of productive viral infection. These studies provided first possible links to some of the vascular abnormalities observed in patients, however, their relevance in vivo remains to be investigated.

  12. Geriatric syndromes--vascular disorders?

    PubMed

    Strandberg, Timo E; Pitkälä, Kaisu H; Tilvis, Reijo S; O'Neill, Desmond; Erkinjuntti, Timo J

    2013-05-01

    The term geriatric syndrome is used to characterize multifactorial clinical conditions among older people which are not subsumed readily into disease entities, but which nevertheless predispose older people to disability and death. Commonly included are frailty, dementia, delirium, incontinence, falls, and dizziness. Geriatric syndromes are common among older people: in a recent survey, 50% of those aged more than 65 had one or more of these conditions. Better methods for prevention and treatment are needed, but current strategies have lacked a coherent conceptual and diagnostic framework. Prevention and interventions need to be targeted at earlier ages, with geriatrics expertise needed in the definition and operationalization of these complex entities. In this review we consolidate evidence that vascular disorders, including vascular ageing and vascular diseases, are key etiological factors of geriatric syndromes. Identifying this vascular dimension would offer opportunities for more efficient preventive strategies and mandates earlier intervention, especially for women, among whom vascular disease is often expressed more insidiously than among men. This would entail a sensitization of the health care system to the systematic detection of the syndromes, which are currently underdiagnosed. Further disentangling of the mechanisms of vascular ageing may offer therapies for vascular diseases and geriatric syndromes alike.

  13. [The future of vascular medicine].

    PubMed

    Kroeger, K; Luther, B

    2014-10-01

    In the future vascular medicine will still have a great impact on health of people. It should be noted that the aging of the population does not lead to a dramatic increase in patient numbers, but will be associated with a changing spectrum of co-morbidities. In addition, vascular medical research has to include the intensive care special features of vascular patients, the involvement of vascular medicine in a holistic concept of fast-track surgery, a geriatric-oriented intensive monitoring and early geriatric rehabilitation. For the future acceptance of vascular medicine as a separate subject area under delimitation of cardiology and radiology is important. On the other hand, the subject is so complex and will become more complex in future specialisations that mixing of surgery and angiology is desirable, with the aim to preserve the vascular surgical knowledge and skills on par with the medical and interventional measures and further develop them. Only large, interdisciplinary guided vascular centres will be able to provide timely diagnosis and therapy, to deal with the growing multi-morbidity of the patient, to perform complex therapies even in an acute emergency and due to sufficient number of cases to present with well-trained and experienced teams. These requirements are mandatory to decrease patients' mortality step by step.

  14. Vascular Injuries: Trends in Management

    PubMed Central

    Wani, Mohd Lateef; Ahangar, Ab Gani; Ganie, Farooq Ahmad; Wani, Shadab Nabi; Wani, Nasir-ud-din

    2012-01-01

    Abstract Vascular injury presents a great challenge to the emergency resident because these injuries require urgent intervention to prevent loss of life or limb. Sometimes serious vascular injury presents with only subtle or occult signs or symptoms. The patient may present weeks or months after initial injury with symptoms of vascular insufficiency, embolization, pseudoaneurysm, arteriovenous fistula etc. Although the majority of vascular injuries are caused by penetrating trauma from gunshot wounds, stabbing or blast injury, the possibility of vascular injury needs to be considered in patients presenting with displaced long bone fractures, crush injury, prolonged immobilization in a fixed position by tight casts or bandages and various invasive procedures. iatrogenic vascular injuries constitute about 10% of cases in most series; however the incidence is an increasing trend because more endovascular procedures such as angioplasty and cardiac catheterization are being performed routinely. Civilian trauma is more frequently seen in young males. However, it can occur at any age due to road accidents, firearms, bomb blasts and diagnostic procedures. Most of the time, civilian trauma causes less tissue damage. There is an epidemic of vascular injuries in Kashmir valley because of problems in law and order in the past two decades. This review deals with the topic in detail. PMID:24350103

  15. Optimizing Nutrient Uptake in Biological Transport Networks

    NASA Astrophysics Data System (ADS)

    Ronellenfitsch, Henrik; Katifori, Eleni

    2013-03-01

    Many biological systems employ complex networks of vascular tubes to facilitate transport of solute nutrients, examples include the vascular system of plants (phloem), some fungi, and the slime-mold Physarum. It is believed that such networks are optimized through evolution for carrying out their designated task. We propose a set of hydrodynamic governing equations for solute transport in a complex network, and obtain the optimal network architecture for various classes of optimizing functionals. We finally discuss the topological properties and statistical mechanics of the resulting complex networks, and examine correspondence of the obtained networks to those found in actual biological systems.

  16. Vascular calcification: Mechanisms of vascular smooth muscle cell calcification.

    PubMed

    Leopold, Jane A

    2015-05-01

    Vascular calcification is highly prevalent and, when present, is associated with major adverse cardiovascular events. Vascular smooth muscle cells play an integral role in mediating vessel calcification by undergoing differentiation to osteoblast-like cells and generating matrix vesicles that serve as a nidus for calcium-phosphate deposition in the vessel wall. Once believed to be a passive process, it is now recognized that vascular calcification is a complex and highly regulated process that involves activation of cellular signaling pathways, circulating inhibitors of calcification, genetic factors, and hormones. This review will examine several of the key mechanisms linking vascular smooth muscle cells to vessel calcification that may be targeted to reduce vessel wall mineralization and, thereby, reduce cardiovascular risk.

  17. Defining excellence in vascular neurosurgery.

    PubMed

    Sanai, Nader; Spetzler, Robert F

    2010-01-01

    Success as a vascular neurosurgeon almost always begins with passion, an inherent love for the work that drives an insatiable desire for personal improvement. A personal definition of excellence in vascular neurosurgery includes several fundamental qualities: mastery of the basics, refinement of technique, advancement of technology, investigative study, advanced decision making, microsurgical innovation, a well-rounded surgical armamentarium, and a lifelong commitment to teaching. Ultimately, the reward for these efforts is the ability to influence generations to come, particularly as one follows the rising careers of former trainees, each redefining the term "excellence" in vascular neurosurgery.

  18. Haemolysis and abnormal haemorheology in sickle cell anaemia.

    PubMed

    Connes, Philippe; Lamarre, Yann; Waltz, Xavier; Ballas, Samir K; Lemonne, Nathalie; Etienne-Julan, Maryse; Hue, Olivier; Hardy-Dessources, Marie-Dominique; Romana, Marc

    2014-05-01

    Although pulmonary hypertension, leg ulcers, priapism, stroke and glomerulopathy in sickle cell anaemia (SCA) result from the adverse effects of chronic haemolysis on vascular function (haemolytic phenotype), osteonecrosis, acute chest syndrome and painful vaso-occlusive crises are caused by abnormal vascular cell adhesion and increased blood viscosity (viscosity-vaso-occlusion phenotype). However, this model with two sub-phenotypes does not take into account the haemorheological dimension. We tested the relationships between the biological parameters reflecting the haemolytic rate (haemolytic component) and red blood cell (RBC) rheological characteristics in 97 adults with SCA. No significant difference in the proportion of patients with low or high haemolytic component in the low and high blood viscosity groups was observed. The RBC elongation index (i.e. deformability) was negatively correlated with the haemolytic component. The RBC aggregates strength (i.e. RBC aggregates robustness) was negatively correlated with RBC elongation index. Sickle RBCs with high density had lower elongation index and higher aggregates strength. In conclusion, (i) the 'haemolytic' phenotype is characterized by decreased RBC deformability and increased RBC aggregates strength and (ii) the viscosity-vaso-occlusive phenotype is characterized by increased RBC deformability but not always by increased blood viscosity. α-thalassaemia modulates the haemorheological properties but other factors seem to be involved.

  19. Plant Phosphoglycerolipids: The Gatekeepers of Vascular Cell Differentiation.

    PubMed

    Gujas, Bojan; Rodriguez-Villalon, Antia

    2016-01-01

    In higher plants, the plant vascular system has evolved as an inter-organ communication network essential to deliver a wide range of signaling factors among distantly separated organs. To become conductive elements, phloem and xylem cells undergo a drastic differentiation program that involves the degradation of the majority of their organelles. While the molecular mechanisms regulating such complex process remain poorly understood, it is nowadays clear that phosphoglycerolipids display a pivotal role in the regulation of vascular tissue formation. In animal cells, this class of lipids is known to mediate acute responses as signal transducers and also act as constitutive signals that help defining organelle identity. Their rapid turnover, asymmetrical distribution across subcellular compartments as well as their ability to rearrange cytoskeleton fibers make phosphoglycerolipids excellent candidates to regulate complex morphogenetic processes such as vascular differentiation. Therefore, in this review we aim to summarize, emphasize and connect our current understanding about the involvement of phosphoglycerolipids in phloem and xylem differentiation.

  20. Plant Phosphoglycerolipids: The Gatekeepers of Vascular Cell Differentiation

    PubMed Central

    Gujas, Bojan; Rodriguez-Villalon, Antia

    2016-01-01

    In higher plants, the plant vascular system has evolved as an inter-organ communication network essential to deliver a wide range of signaling factors among distantly separated organs. To become conductive elements, phloem and xylem cells undergo a drastic differentiation program that involves the degradation of the majority of their organelles. While the molecular mechanisms regulating such complex process remain poorly understood, it is nowadays clear that phosphoglycerolipids display a pivotal role in the regulation of vascular tissue formation. In animal cells, this class of lipids is known to mediate acute responses as signal transducers and also act as constitutive signals that help defining organelle identity. Their rapid turnover, asymmetrical distribution across subcellular compartments as well as their ability to rearrange cytoskeleton fibers make phosphoglycerolipids excellent candidates to regulate complex morphogenetic processes such as vascular differentiation. Therefore, in this review we aim to summarize, emphasize and connect our current understanding about the involvement of phosphoglycerolipids in phloem and xylem differentiation. PMID:26904069

  1. Ceacam1 deletion causes vascular alterations in large vessels.

    PubMed

    Najjar, Sonia M; Ledford, Kelly J; Abdallah, Simon L; Paus, Alexander; Russo, Lucia; Kaw, Meenakshi K; Ramakrishnan, Sadeesh K; Muturi, Harrison T; Raphael, Christian K; Lester, Sumona Ghosh; Heinrich, Garrett; Pierre, Sandrine V; Benndorf, Ralf; Kleff, Veronika; Jaffa, Ayad A; Lévy, Emile; Vazquez, Guillermo; Goldberg, Ira J; Beauchemin, Nicole; Scalia, Rosario; Ergün, Süleyman

    2013-08-15

    Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) promotes hepatic insulin clearance and endothelial survival. However, its role in the morphology of macrovessels remains unknown. Mice lacking Ceacam1 (Cc1-/-) exhibit hyperinsulinemia, which causes insulin resistance and fatty liver. With increasing evidence of an association among hyperinsulinemia, fatty liver disease, and atherosclerosis, we investigated whether Cc1-/- exhibited vascular lesions in atherogenic-prone aortae. Histological analysis revealed impaired endothelial integrity with restricted fat deposition and aortic plaque-like lesions in Cc1-/- aortae, likely owing to their limited lipidemia. Immunohistochemical analysis indicated macrophage deposition, and in vitro studies showed increased leukocyte adhesion to aortic wall, mediated in part by elevation in vascular cell adhesion molecule 1 levels. Basal aortic eNOS protein and NO content were reduced, in parallel with reduced Akt/eNOS and Akt/Foxo1 phosphorylation. Ligand-induced vasorelaxation was compromised in aortic rings. Increased NADPH oxidase activity and plasma 8-isoprostane levels revealed oxidative stress and lipid peroxidation in Cc1-/- aortae. siRNA-mediated CEACAM1 knockdown in bovine aortic endothelial cells adversely affected insulin's stimulation of IRS-1/PI 3-kinase/Akt/eNOS activation by increasing IRS-1 binding to SHP2 phosphatase. This demonstrates that CEACAM1 regulates both endothelial cell autonomous and nonautonomous mechanisms involved in vascular morphology and NO production in aortae. Systemic factors such as hyperinsulinemia could contribute to the pathogenesis of these vascular abnormalities. Cc1-/- mice provide a first in vivo demonstration of distinct CEACAM1-dependent hepatic insulin clearance linking hepatic to macrovascular abnormalities.

  2. Brain abnormalities in murderers indicated by positron emission tomography.

    PubMed

    Raine, A; Buchsbaum, M; LaCasse, L

    1997-09-15

    Murderers pleading not guilty by reason of insanity (NGRI) are thought to have brain dysfunction, but there have been no previous studies reporting direct measures of both cortical and subcortical brain functioning in this specific group. Positron emission tomography brain imaging using a continuous performance challenge task was conducted on 41 murderers pleading not guilty by reason of insanity and 41 age- and sex-matched controls. Murderers were characterized by reduced glucose metabolism in the prefrontal cortex, superior parietal gyrus, left angular gyrus, and the corpus callosum, while abnormal asymmetries of activity (left hemisphere lower than right) were also found in the amygdala, thalamus, and medial temporal lobe. These preliminary findings provide initial indications of a network of abnormal cortical and subcortical brain processes that may predispose to violence in murderers pleading NGRI.

  3. Periodontal growth in areas of vascular malformation in patients with Sturge-Weber syndrome: a management protocol.

    PubMed

    Pontes, Flávia Sirotheau Corrêa; Conte Neto, Nicolau; da Costa, Rodrigo Moreira Bringel; Loureiro, Arlison Miranda; do Nascimento, Liliane Silva; Pontes, Hélder Antônio Rebelo

    2014-01-01

    Sturge-Weber syndrome (SWS) is a very rare condition characterized by abnormal vascular formations that encompass several manifestations: cutaneous, neurologic, ocular, and oral. Neurologic conditions are the most important factor, especially epilepsy, which frequently leads patients to make use of anticonvulsants. These drugs are capable of inducing abnormal tissue growth in the oral cavity that can be situated over areas with vascular malformation, requiring special attention by the clinician. This report describes 1 case of SWS and performs a literature review of treatments for this condition, providing a protocol of treatment for these clinical situations.

  4. Vascular remodeling in the growth hormone transgenic mouse.

    PubMed

    Dilley, R J; Schwartz, S M

    1989-11-01

    Using mice transgenic for the growth hormone gene (TGHM), we have studied the effects of a systemic elevation of growth hormone on vascular growth with the aim of investigating the role of vascular mass changes in producing hypertension. In contrast to human acromegaly or gigantism, there was no elevation of blood pressure in TGHM, but there were significant increases in vascular wall mass. In accordance with a presumably increased perfusion of larger organs, the medial cross-sectional areas of thoracic aorta and mesenteric resistance vessels were greater in the TGHM. These differences could be normalized in the aorta by body weight and in the mesenteric vessel by small intestine weight. Furthermore, the brain was not significantly heavier in the TGHM, and their carotid and cerebral vessels also were not larger. Wall-to-lumen ratios were similar in the aorta, carotid, and middle cerebral arteries suggesting that wall stress was the controlling factor in wall thickness. Surprisingly, the mesenteric vessels had increased wall-to-lumen ratio, which was similar to that seen in hypertensive vascular remodeling but in a normotensive animal. In an attempt to explain this finding it was noted that the pattern of mesenteric vascular networks and even organized structure within the vessel wall itself appeared to be fixed, perhaps by genetic mechanisms. Thus, vascular network structure may be a potentially limiting factor in the ability of the vessel wall to remodel and may have been responsible for the greater wall-to-lumen ratio in TGHM mesenteric vessels. A similar situation in human acromegaly or gigantism could result in a circulation marginally able to correct for other demands on blood flow resulting in about one third of cases being hypertensive. PMID:2805241

  5. Concomitant axial cineangiography and barium esophagography in the evaluation of vascular rings.

    PubMed

    Tonkin, I L; Elliott, L P; Bargeron, L M

    1980-04-01

    Six vascular rings were evaluated using axial biplane cineangiography and concomitant barium esophagography. Three patients had a double aortic arch, two had a right aortic arch and aberrant left subclavian artery with a foreshortened left ligamentum arteriosum, and one had a pulmonary vascular sling. Barium was administered in the esophagus of the anesthetized patient followed by cineangiography. Five patients were evaluated using both the standard and four-chamber projection, while the sixth patient with the pulmonary sling was evaluated in the standard and sitting projection. With the four-chamber view, vascular rings were exposed and atypical features such as a small right aortic arch component and branch stenoses of the brachiocephalic arteries were revealed. Axial views with an esophagogram allow easier morphologic analysis and more precise definition of the vascular abnormality than conventional views. PMID:7360983

  6. Phenotypic abnormalities: terminology and classification.

    PubMed

    Merks, Johannes H M; van Karnebeek, Clara D M; Caron, Hubert N; Hennekam, Raoul C M

    2003-12-15

    Clinical morphology has proved essential for the successful delineation of hundreds of syndromes and as a powerful instrument for detecting (candidate) genes (Gorlin et al. [2001]; Syndromes of the Head and Neck; Oxford: Oxford University Press. 1 p]. The major approach to reach this has been careful clinical evaluations of patients, focused on congenital anomalies. A similar careful physical examination performed in patients, who have been treated for childhood cancer, may allow detection of concurrent patterns of anomalies and provide clues for causative genes. In the past, several studies were performed describing the prevalence of anomalies in patients with cancer. However, in most studies, it was not possible to indicate the biologic relevance of the recorded anomalies, or to judge their relative importance. Are the detected anomalies common variants, and should they thus be regarded as normal, or are they minor anomalies or true abnormalities, indicating a possible developmental cause? Classification of items in the categories of common variants (disturbances of phenogenesis with a prevalence >4%), minor anomalies (disturbances of phenogenesis with a prevalence abnormal physical findings by a nomenclature for errors of morphogenesis detectable on surface examination, and secondly a uniform classification system. This should allow investigators to evaluate systematically the presence of patterns in phenotypic anomalies, in the general population, and in patients with various disorders, suspected to be a developmental anomaly. Also

  7. BMP signaling in vascular diseases.

    PubMed

    Cai, Jie; Pardali, Evangelia; Sánchez-Duffhues, Gonzalo; ten Dijke, Peter

    2012-07-01

    Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-β (TGF-β) family that signal via type I and type II serine/threonine kinase receptors and intracellular Smad transcription factors. BMPs are multifunctional regulators of development and tissue homeostasis and they were initially characterized as inducers of bone regeneration. Genetic studies in humans and mice showed that perturbations in BMP signaling lead to various diseases, such as skeletal diseases, vascular diseases and cancer. Mutations in BMP type II receptor and BMP type I receptor/activin receptor-like kinase 1 have been linked to pulmonary arterial hypertension and hereditary hemorrhagic telangiectasia, respectively. BMPs have also been implicated in promoting vascular calcification and tumor angiogenesis. In this review we discuss the role of BMP signaling in vascular diseases and the value of BMP signaling as a vascular disease marker or a therapeutic target. PMID:22710160

  8. Biomaterials for vascular tissue engineering

    PubMed Central

    Ravi, Swathi; Chaikof, Elliot L

    2010-01-01

    Cardiovascular disease is the leading cause of mortality in the USA. The limited availability of healthy autologous vessels for bypass grafting procedures has led to the fabrication of prosthetic vascular conduits. While synthetic polymers have been extensively studied as substitutes in vascular engineering, they fall short of meeting the biological challenges at the blood–material interface. Various tissue engineering strategies have emerged to address these flaws and increase long-term patency of vascular grafts. Vascular cell seeding of scaffolds and the design of bioactive polymers for in situ arterial regeneration have yielded promising results. This article describes the advances made in biomaterials design to generate suitable materials that not only match the mechanical properties of native vasculature, but also promote cell growth, facilitate extracellular matrix production and inhibit thrombogenicity. PMID:20017698

  9. How to Prevent Vascular Disease

    MedlinePlus

    ... or 911 immediately. @ 2016 Vascular Cures is a tax-exempt, nonprofit organization tax ID#: 94-2825216 as described in the Section ... 3) of the Internal Revenue Code. Donations are tax deductible. 555 Price Ave., Suite 180, Redwood City, ...

  10. Construction of three-dimensional vascularized cardiac tissue with cell sheet engineering.

    PubMed

    Sakaguchi, Katsuhisa; Shimizu, Tatsuya; Okano, Teruo

    2015-05-10

    Construction of three-dimensional (3D) tissues with pre-isolated cells is a promising achievement for novel medicine and drug-discovery research. Our laboratory constructs 3D tissues with an innovative and unique method for layering multiple cell sheets. Cell sheets maintain a high-efficiently regenerating function, because of the higher cell density and higher transplantation efficiency, compared to other cell-delivery methods. Cell sheets have already been applied in clinical applications for regenerative medicine in treating patients with various diseases. Therefore, in our search to develop a more efficient treatment with cell sheets, we are constructing 3D tissues by layering cell sheets. Native animal tissues and organs have an abundance of capillaries to supply oxygen and nutrients, and to remove waste molecules. In our investigation of vascularized cardiac cell sheets, we have found that endothelial cells within cell sheets spontaneously form blood vessel networks as in vivo capillaries. To construct even thicker 3D tissues by layering multiple cell sheets, it is critical to have a medium or blood flow within the vascular networks of the cell sheets. Therefore, to perfuse medium or blood in the cell sheet vascular network to maintain the viability of all cells, we developed two types of vascular beds; (1) a femoral muscle-based vascular bed, and (2) a synthetic collagen gel-based vascular bed. Both vascular beds successfully provide the critical flow of culture medium, which allows 12-layer cell sheets to survive. Such bioreactor systems, when combined with cell sheet engineering techniques, have produced functional vascularized 3D tissues. Here we explain and discuss the various processes to obtain vascular networks by properly connecting cell sheets and the engineering of 3D tissues.

  11. Vascular heterogeneity in the kidney.

    PubMed

    Molema, Grietje; Aird, William C

    2012-03-01

    Blood vessels and their endothelial lining are uniquely adapted to the needs of the underlying tissue. The structure and function of the vasculature varies both between and within different organs. In the kidney, the vascular architecture is designed to function both in oxygen/nutrient delivery and filtration of blood according to the homeostatic needs of the body. Here, we review spatial and temporal differences in renal vascular phenotypes in both health and disease.

  12. [Renal abnormalities in ankylosing spondylitis].

    PubMed

    Samia, Barbouch; Hazgui, Faiçal; Abdelghani, Khaoula Ben; Hamida, Fethi Ben; Goucha, Rym; Hedri, Hafedh; Taarit, Chokri Ben; Maiz, Hedi Ben; Kheder, Adel

    2012-07-01

    We will study the epidemiologic, clinical, biological, therapeutic, prognostic characteristics and predictive factors of development of nephropathy in ankylosing spondylitis patients. We retrospectively reviewed the medical record of 32 cases with renal involvement among 212 cases of ankylosing spondylitis followed in our service during the period spread out between 1978 and 2006. The renal involvement occurred in all patients a mean of 12 years after the clinical onset of the rheumatic disease. Thirty-two patients presented one or more signs of renal involvement: microscopic hematuria in 22 patients, proteinuria in 23 patients, nephrotic syndrome in 11 patients and decreased renal function in 24 patients (75%). Secondary renal amyloidosis (13 patients), which corresponds to a prevalence of 6,1% and tubulointerstitial nephropathy (7 patients) were the most common cause of renal involvement in ankylosing spondylitis followed by IgA nephropathy (4 patients). Seventeen patients evolved to the end stage renal disease after an average time of 29.8 ± 46 months. The average follow-up of the patients was 4,4 years. By comparing the 32 patients presenting a SPA and renal disease to 88 with SPA and without nephropathy, we detected the predictive factors of occurred of nephropathy: tobacco, intense inflammatory syndrome, sacroileite stage 3 or 4 and presence of column bamboo. The finding of 75% of the patients presented a renal failure at the time of the diagnosis of renal involvement suggests that evidence of renal abnormality involvement should be actively sought in this disease. PMID:22520483

  13. [Renal abnormalities in ankylosing spondylitis].

    PubMed

    Samia, Barbouch; Hazgui, Faiçal; Abdelghani, Khaoula Ben; Hamida, Fethi Ben; Goucha, Rym; Hedri, Hafedh; Taarit, Chokri Ben; Maiz, Hedi Ben; Kheder, Adel

    2012-07-01

    We will study the epidemiologic, clinical, biological, therapeutic, prognostic characteristics and predictive factors of development of nephropathy in ankylosing spondylitis patients. We retrospectively reviewed the medical record of 32 cases with renal involvement among 212 cases of ankylosing spondylitis followed in our service during the period spread out between 1978 and 2006. The renal involvement occurred in all patients a mean of 12 years after the clinical onset of the rheumatic disease. Thirty-two patients presented one or more signs of renal involvement: microscopic hematuria in 22 patients, proteinuria in 23 patients, nephrotic syndrome in 11 patients and decreased renal function in 24 patients (75%). Secondary renal amyloidosis (13 patients), which corresponds to a prevalence of 6,1% and tubulointerstitial nephropathy (7 patients) were the most common cause of renal involvement in ankylosing spondylitis followed by IgA nephropathy (4 patients). Seventeen patients evolved to the end stage renal disease after an average time of 29.8 ± 46 months. The average follow-up of the patients was 4,4 years. By comparing the 32 patients presenting a SPA and renal disease to 88 with SPA and without nephropathy, we detected the predictive factors of occurred of nephropathy: tobacco, intense inflammatory syndrome, sacroileite stage 3 or 4 and presence of column bamboo. The finding of 75% of the patients presented a renal failure at the time of the diagnosis of renal involvement suggests that evidence of renal abnormality involvement should be actively sought in this disease.

  14. The XXXXY Sex Chromosome Abnormality

    PubMed Central

    Barr, M. L.; Carr, D. H.; Pozsonyi, J.; Wilson, R. A.; Dunn, H. G.; Jacobson, T. S.; Miller, J. R.; Chown, B.

    1962-01-01

    The most common sex chromosome complex in sex chromatin-positive males with Klinefelter's syndrome is XXY. When the complex is XXYY or XXXY, the clinical findings do not seem to differ materially from those seen in XXY subjects, although more patients with these intersexual chromosome complements need to be studied to establish possible phenotypical expressions of the chromosomal variants. Two male children with an XXXXY sex chromosome abnormality are described. The data obtained from the study of these cases and five others described in the literature suggest that the XXXXY patient is likely to have congenital defects not usually seen in the common form of the Klinefelter syndrome. These include a triad of (1) skeletal anomalies (including radioulnar synostosis), (2) hypogenitalism (hypoplasia of penis and scrotum, incomplete descent of testes and defective prepubertal development of seminiferous tubules), and (3) greater risk of severe mental deficiency. That the conclusions are based on data from a small number of patients is emphasized, together with the need for a cytogenetic survey of a large control or unselected population. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8Fig. 9Fig. 10 PMID:13969480

  15. Remodelling the vascular microenvironment of glioblastoma with alpha-particles

    PubMed Central

    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.

    2016-01-01

    Rationale Tumors escape anti-angiogenic therapy by activation of pro-angiogenic signaling pathways. Bevacizumab is approved for the treatment of recurrent glioblastoma, but patients inevitably develop resistance to this angiogenic inhibitor. We investigated targeted α-particle therapy with 225Ac-E4G10 as an anti-vascular approach and previously showed increased survival and tumor control in a high-grade transgenic orthotopic glioblastoma model. Here we investigate changes in tumor-vascular morphology and functionality caused by 225Ac-E4G10. Methods We investigated remodeling of tumor microenvironment in transgenic Ntva glioblastoma mice using a therapeutic 7.4 kBq dose of 225Ac-E4G10. Immunofluorescence and immunohistochemical analyses imaged morphological changes in the tumor blood brain barrier microenvironment. Multi-color flow cytometry quantified the endothelial progenitor cell population in the bone marrow. Diffusion-weighted magnetic resonance imaged functional changes of the tumor vascular network. Results The mechanism of drug action is a combination of glioblastoma vascular microenvironment remodeling, edema relief, 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 was lessened and resulted in increased perfusion and reduced diffusion. Pharmacological uptake of dasatinib into tumor was enhanced following α-particle therapy. Conclusion Targeted anti-vascular 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. PMID:27261519

  16. Maternal diabetes: effects on embryonic vascular development--a vascular endothelial growth factor-A-mediated process.

    PubMed

    Madri, Joseph A; Enciso, Josephine; Pinter, Emese

    2003-01-01

    Major congenital malformations, many of which result from abnormal cardiovascular patterning, remain the leading cause in infant mortality and morbidity. Targeted mutations of several genes (including VEGF and VEGF receptors) and certain teratogenic agents (including excess alpha-D-glucose) give rise to embryonic lethal phenotypes associated with failure in the formation of a functional vitelline circulation and aberrant organogenesis. Our work to date has demonstrated that yolk sac vasculopathy and failure of endocardial cushion epithelial-mesenchymal transformation occurs in hyperglycemic conditions in murine whole conceptus culture and in embryos from streptozotocin-induced diabetic mice. These cardiovascular abnormalities are associated with changes in expression and phosphorylation state of adhesion molecules such as platelet endothelial growth factor-1 and expression of growth factors such as vascular endothelial growth factor (VEGF-A). Further understanding of the effects of maternal diabetes on yolk sac and embryonic vasculogenesis/angiogenesis and organogenesis may lead to novel approaches in treating and preventing major birth defects.

  17. Multimodality imaging of vascular anomalies.

    PubMed

    Restrepo, Ricardo

    2013-03-01

    Vascular malformations and hemangiomas are common in children but remain a source of confusion during diagnosis, in part because of the lack of a uniform terminology. With the existing treatments for hemangiomas and vascular malformations, it is important to make the correct diagnosis initially to prevent adverse physical and emotional sequelae in not only the child but also the family. The diagnosis of vascular malformations is made primarily by the clinician and based on the physical exam. Imaging is carried out using predominantly ultrasound (US) and magnetic resonance imaging (MRI), which are complementary modalities. In most cases of vascular anomalies, US is the first line of imaging as it is readily available, less expensive, lacks ionizing radiation and does not require sedation. MRI is also of great help for further characterizing the lesions. Conventional arteriography is reserved for cases that require therapeutic intervention, more commonly for arteriovenous malformations. Radiographs usually play no role in diagnosing vascular anomalies in children. In this article, the author describes the terminology and types of hemangiomas and vascular malformations and their clinical, histological features, as well as the imaging approach and appearance.

  18. Self-Replenishing Vascularized Fouling-Release Surfaces

    SciTech Connect

    Howell, C; Vu, TL; Lin, JJ; Kolle, S; Juthani, N; Watson, E; Weaver, JC; Alvarenga, J; Aizenberg, J

    2014-08-13

    Inspired by the long-term effectiveness of living antifouling materials, we have developed a method for the self-replenishment of synthetic biofouling-release surfaces. These surfaces are created by either molding or directly embedding 3D vascular systems into polydimethylsiloxane (PDMS) and filling them with a silicone oil to generate a nontoxic oil-infused material. When replenished with silicone oil from an outside source, these materials are capable of self-lubrication and continuous renewal of the interfacial fouling-release layer. Under accelerated lubricant loss conditions, fully infused vascularized samples retained significantly more lubricant than equivalent nonvascularized controls. Tests of lubricant-infused PDMS in static cultures of the infectious bacteria Staphylococcus aureus and Escherichia coli as well as the green microalgae Botryococcus braunii, Chlamydomonas reinhardtii, Dunaliella sauna, and Nannochloropsis oculata showed a significant reduction in biofilm adhesion compared to PDMS and glass controls containing no lubricant. Further experiments on vascularized versus nonvascularized samples that had been subjected to accelerated lubricant evaporation conditions for up to 48 h showed significantly less biofilm adherence on the vascularized surfaces. These results demonstrate the ability of an embedded lubricant-filled vascular network to improve the longevity of fouling-release surfaces.

  19. Self-Replenishing Vascularized Fouling-Release Surfaces

    SciTech Connect

    Howell, Caitlin; Vu, Thy L.; Lin, Jennifer J.; Kolle, Stefan; Juthani, Nidhi; Watson, Emily; Weaver, James C.; Alvarenga, Jack; Aizenberg, Joanna

    2014-08-13

    Inspired by the long-term effectiveness of living antifouling materials, we have developed a method for the selfreplenishment of synthetic biofouling-release surfaces. These surfaces are created by either molding or directly embedding 3D vascular systems into polydimethylsiloxane (PDMS) and filling them with a silicone oil to generate a nontoxic oil-infused material. When replenished with silicone oil from an outside source, these materials are capable of self-lubrication and continuous renewal of the interfacial fouling-release layer. Under accelerated lubricant loss conditions, fully infused vascularized samples retained significantly more lubricant than equivalent nonvascularized controls. Tests of lubricant-infused PDMS in static cultures of the infectious bacteria Staphylococcus aureus and Escherichia coli as well as the green microalgae Botryococcus braunii, Chlamydomonas reinhardtii, Dunaliella salina, and Nannochloropsis oculata showed a significant reduction in biofilm adhesion compared to PDMS and glass controls containing no lubricant. Further experiments on vascularized versus nonvascularized samples that had been subjected to accelerated lubricant evaporation conditions for up to 48 h showed significantly less biofilm adherence on the vascularized surfaces. These results demonstrate the ability of an embedded lubricant-filled vascular network to improve the longevity of fouling-release surfaces.

  20. Self-Replenishing Vascularized Fouling-Release Surfaces

    DOE PAGES

    Howell, Caitlin; Vu, Thy L.; Lin, Jennifer J.; Kolle, Stefan; Juthani, Nidhi; Watson, Emily; Weaver, James C.; Alvarenga, Jack; Aizenberg, Joanna

    2014-08-13

    Inspired by the long-term effectiveness of living antifouling materials, we have developed a method for the selfreplenishment of synthetic biofouling-release surfaces. These surfaces are created by either molding or directly embedding 3D vascular systems into polydimethylsiloxane (PDMS) and filling them with a silicone oil to generate a nontoxic oil-infused material. When replenished with silicone oil from an outside source, these materials are capable of self-lubrication and continuous renewal of the interfacial fouling-release layer. Under accelerated lubricant loss conditions, fully infused vascularized samples retained significantly more lubricant than equivalent nonvascularized controls. Tests of lubricant-infused PDMS in static cultures of the infectiousmore » bacteria Staphylococcus aureus and Escherichia coli as well as the green microalgae Botryococcus braunii, Chlamydomonas reinhardtii, Dunaliella salina, and Nannochloropsis oculata showed a significant reduction in biofilm adhesion compared to PDMS and glass controls containing no lubricant. Further experiments on vascularized versus nonvascularized samples that had been subjected to accelerated lubricant evaporation conditions for up to 48 h showed significantly less biofilm adherence on the vascularized surfaces. These results demonstrate the ability of an embedded lubricant-filled vascular network to improve the longevity of fouling-release surfaces.« less

  1. Extracellular Vesicles and Vascular Injury: New Insights for Radiation Exposure.

    PubMed

    Flamant, Stéphane; Tamarat, Radia

    2016-08-01

    This article reviews our current knowledge about cell-derived extracellular vesicles (EVs), including microparticles and exosomes, and their emergence as mediators of a new important mechanism of cell-to-cell communication. Particular emphasis has been given to the increasing involvement of EVs in the field of radiation-induced vascular injury. Although EVs have been considered for a long time as cell "dust", they in fact precisely reflect the physiological state of the cells. The role of microparticles and exosomes in mediating vascular dysfunction suggests that they may represent novel pathways in short- or long-distance paracrine intercellular signaling in vascular environment. In this article, the mechanisms involved in the biogenesis of microparticles and exosomes, their composition and participation in the pathogenesis of vascular dysfunction are discussed. Furthermore, this article highlights the concept of EVs as potent vectors of biological information and protagonists of an intercellular communication network. Special emphasis is made on EV-mediated microRNA transfer and on the principal consequences of such signal exchange on vascular injury and radiation-induced nontargeted effect. The recent progress in elucidating the biology of EVs has provided new insights for the field of radiation, advancing their use as diagnostic biomarkers or in therapeutic interventions. PMID:27459703

  2. Hierarchical Fabrication of Engineered Vascularized Bone Biphasic Constructs via Dual 3D Bioprinting: Integrating Regional Bioactive Factors into Architectural Design.

    PubMed

    Cui, Haitao; Zhu, Wei; Nowicki, Margaret; Zhou, Xuan; Khademhosseini, Ali; Zhang, Lijie Grace

    2016-09-01

    A biphasic artificial vascularized bone construct with regional bioactive factors is presented using dual 3D bioprinting platform technique, thereby forming a large functional bone grafts with organized vascular networks. Biocompatible mussel-inspired chemistry and "thiol-ene" click reaction are used to regionally immobilize bioactive factors during construct fabrication for modulating or improving cellular events.

  3. Abnormal aortic fatty acid composition and small artery function in offspring of rats fed a high fat diet in pregnancy

    PubMed Central

    Ghosh, P; Bitsanis, D; Ghebremeskel, K; Crawford, M A; Poston, L

    2001-01-01

    Disturbances of the in utero environment are associated with an increased risk of cardiovascular disease in adulthood. In this study we have determined whether abnormal vascular function in the adult offspring of rats fed a high saturated fat diet in pregnancy is associated with altered plasma lipids or vascular fatty acid content. Female Sprague-Dawley rats were fed a breeding diet (4 % fat) or a diet high in saturated fat (20 % fat) for 10 days prior to and throughout pregnancy, and during weaning. Female offspring were then fed a maintenance diet (3 % fat) until 160 days of age. Endothelium-dependent relaxation induced by acetylcholine was blunted in isolated branches of the femoral artery from 160-day-old female offspring of dams fed the saturated fat diet when compared with female offspring of dams fed the breeding diet. These offspring exhibited elevated plasma triglyceride and reduced plasma high density lipoprotein cholesterol concentrations. The fatty acid composition of the aortas was abnormal, with a marked reduction in the content of arachidonic and docosahexaenoic acids. This study demonstrates that a high fat diet in pregnant rats produces abnormal vascular function, plasma lipid disturbances and altered vascular fatty acid content in their female offspring during adulthood. PMID:11410637

  4. Vascular Extracellular Matrix and Arterial Mechanics

    PubMed Central

    WAGENSEIL, JESSICA E.; MECHAM, ROBERT P.

    2009-01-01

    An important factor in the transition from an open to a closed circulatory system was a change in vessel wall structure and composition that enabled the large arteries to store and release energy during the cardiac cycle. The component of the arterial wall in vertebrates that accounts for these properties is the elastic fiber network organized by medial smooth muscle. Beginning with the onset of pulsatile blood flow in the developing aorta, smooth muscle cells in the vessel wall produce a complex extracellular matrix (ECM) that will ultimately define the mechanical properties that are critical for proper function of the adult vascular system. This review discusses the structural ECM proteins in the vertebrate aortic wall and will explore how the choice of ECM components has changed through evolution as the cardiovascular system became more advanced and pulse pressure increased. By correlating vessel mechanics with physiological blood pressure across animal species and in mice with altered vessel compliance, we show that cardiac and vascular development are physiologically coupled, and we provide evidence for a universal elastic modulus that controls the parameters of ECM deposition in vessel wall development. We also discuss mechanical models that can be used to design better tissue-engineered vessels and to test the efficacy of clinical treatments. PMID:19584318

  5. Retinal Vascular Fractals and Cognitive Impairment

    PubMed Central

    Ong, Yi-Ting; Hilal, Saima; Cheung, Carol Yim-lui; Xu, Xin; Chen, Christopher; Venketasubramanian, Narayanaswamy; Wong, Tien Yin; Ikram, Mohammad Kamran

    2014-01-01

    Background Retinal microvascular network changes have been found in patients with age-related brain diseases such as stroke and dementia including Alzheimer's disease. We examine whether retinal microvascular network changes are also present in preclinical stages of dementia. Methods This is a cross-sectional study of 300 Chinese participants (age: ≥60 years) from the ongoing Epidemiology of Dementia in Singapore study who underwent detailed clinical examinations including retinal photography, brain imaging and neuropsychological testing. Retinal vascular parameters were assessed from optic disc-centered photographs using a semiautomated program. A comprehensive neuropsychological battery was administered, and cognitive function was summarized as composite and domain-specific Z-scores. Cognitive impairment no dementia (CIND) and dementia were diagnosed according to standard diagnostic criteria. Results Among 268 eligible nondemented participants, 78 subjects were categorized as CIND-mild and 69 as CIND-moderate. In multivariable adjusted models, reduced retinal arteriolar and venular fractal dimensions were associated with an increased risk of CIND-mild and CIND-moderate. Reduced fractal dimensions were associated with poorer cognitive performance globally and in the specific domains of verbal memory, visuoconstruction and visuomotor speed. Conclusion A sparser retinal microvascular network, represented by reduced arteriolar and venular fractal dimensions, was associated with cognitive impairment, suggesting that early microvascular damage may be present in preclinical stages of dementia. PMID:25298774

  6. Differentiation of Multipotent Vascular Stem Cells Contributes to Vascular Diseases

    PubMed Central

    Tang, Zhenyu; Wang, Aijun; Yuan, Falei; Yan, Zhiqiang; Liu, Bo; Chu, Julia S.; Helms, Jill A.

    2012-01-01

    It is generally accepted that the de-differentiation of smooth muscle cells (SMCs) from contractile to proliferative/synthetic phenotype has an important role during vascular remodeling and diseases. Here we provide evidence that challenges this theory. We identify a new type of multipotent vascular stem cell (MVSC) in blood vessel wall. MVSCs express markers including Sox17, Sox10 and S100β, are cloneable, have telomerase activity, and can differentiate into neural cells and mesenchymal stem cell (MSC)-like cells that subsequently differentiate into SMCs. On the other hand, we use lineage tracing with smooth muscle myosin heavy chain as a marker to show that MVSCs and proliferative or synthetic SMCs do not arise from the de-differentiation of mature SMCs. Upon vascular injuries, MVSCs, instead of SMCs, become proliferative, and MVSCs can differentiate into SMCs and chondrogenic cells, thus contributing to vascular remodeling and neointimal hyperplasia. These findings support a new hypothesis that the differentiation of MVSCs, rather than the de-differentiation of SMCs, contributes to vascular remodeling and diseases. PMID:22673902

  7. Early experience on peripheral vascular application of the vascular plugs

    PubMed Central

    Rohit, Manoj Kumar; Sinha, Alok Kumar; Kamana, Naveen Krishna

    2013-01-01

    Background Transcatheter closure of various congenital and acquired vascular malformations with Amplatzer Vascular plugs I and II has been established. Here we present our experience with device closure. Materials and methods Between October 2006 and August 2012, nine (three males and six females) patients aged between 11 months and 62 years (mean age 19 years) underwent percutaneous device closure with AVP I and II vascular plugs for congenital and acquired arteriovenous malformation and cardiac diverticulum are presented here. Results One case of coronary cameral fistula, four cases of pulmonary arteriovenous fistula, one case of large major aortopulmonary collaterals (in tetralogy of Fallot closed before intracardiac repair), one case of congenital cardiac diverticulum, one case of fistula between external carotid artery and internal jugular vein and one case of iatrogenic carotid jugular fistula were successfully closed with AVP I and II plugs. Overall in nine cases, 16 AVP I and II plugs were deployed to occlude feeding vessels and one cardiac diverticulum. The technical success rate was 100%. No major complications were observed. Conclusion Amplatzer vascular plugs can be used successfully for closure of various congenital and acquired vascular malformations with good result. PMID:24206877

  8. Vascular endothelial growth factor coordinates islet innervation via vascular scaffolding

    PubMed Central

    Reinert, Rachel B.; Cai, Qing; Hong, Ji-Young; Plank, Jennifer L.; Aamodt, Kristie; Prasad, Nripesh; Aramandla, Radhika; Dai, Chunhua; Levy, Shawn E.; Pozzi, Ambra; Labosky, Patricia A.; Wright, Christopher V. E.; Brissova, Marcela; Powers, Alvin C.

    2014-01-01

    Neurovascular alignment is a common anatomical feature of organs, but the mechanisms leading to this arrangement are incompletely understood. Here, we show that vascular endothelial growth factor (VEGF) signaling profoundly affects both vascularization and innervation of the pancreatic islet. In mature islets, nerves are closely associated with capillaries, but the islet vascularization process during embryonic organogenesis significantly precedes islet innervation. Although a simple neuronal meshwork interconnects the developing islet clusters as they begin to form at E14.5, the substantial ingrowth of nerve fibers into islets occurs postnatally, when islet vascularization is already complete. Using genetic mouse models, we demonstrate that VEGF regulates islet innervation indirectly through its effects on intra-islet endothelial cells. Our data indicate that formation of a VEGF-directed, intra-islet vascular plexus is required for development of islet innervation, and that VEGF-induced islet hypervascularization leads to increased nerve fiber ingrowth. Transcriptome analysis of hypervascularized islets revealed an increased expression of extracellular matrix components and axon guidance molecules, with these transcripts being enriched in the islet-derived endothelial cell population. We propose a mechanism for coordinated neurovascular development within pancreatic islets, in which endocrine cell-derived VEGF directs the patterning of intra-islet capillaries during embryogenesis, forming a scaffold for the postnatal ingrowth of essential autonomic nerve fibers. PMID:24574008

  9. Vascular hand-arm vibration syndrome--magnetic resonance angiography.

    PubMed

    Poole, C J M; Cleveland, T J

    2016-01-01

    The diagnosis of vascular hand-arm vibration syndrome (HAVS) requires consistent symptoms, photographic evidence of digital blanching and sufficient exposure to hand-transmitted vibration (HTV; A(8) > 2.5 m/s2). There is no reliable quantitative investigation for distinguishing HAVS from other causes of Raynaud's phenomenon and from normal individuals. Hypothenar and thenar hammer syndromes produce similar symptoms to HAVS but are difficult to diagnose clinically and may be confused with HAVS. Magnetic resonance angiography (MRA) is a safe and minimally invasive method of visualizing blood vessels. Three cases of vascular HAVS are described in which MRA revealed occlusions of the ulnar, radial and superficial palmar arteries. It is proposed that HTV was the cause of these occlusions, rather than blows to the hand unrelated to vibration, the assumed mechanism for the hammer syndromes. All three cases were advised not to expose their hands to HTV despite one of them being at Stockholm vascular stage 2 (early). MRA should be the investigation of choice for stage 2 vascular HAVS or vascular HAVS with unusual features or for a suspected hammer syndrome. The technique is however technically challenging and best done in specialist centres in collaboration with an occupational physician familiar with the examination of HAVS cases. Staging for HAVS should be developed to include anatomical arterial abnormalities as well as symptoms and signs of blanching. Workers with only one artery supplying a hand, or with only one palmar arch, may be at increased risk of progression and therefore should not be exposed to HTV irrespective of their Stockholm stage.

  10. Immune Abnormalities in Patients with Autism.

    ERIC Educational Resources Information Center

    Warren, Reed P.; And Others

    1986-01-01

    A study of 31 autistic patients (3-28 years old) has revealed several immune-system abnormalities, including decreased numbers of T lymphocytes and an altered ratio of helper-to-suppressor T cells. Immune-system abnormalities may be directly related to underlying biologic processes of autism or an indirect reflection of the actual pathologic…

  11. An Abnormal Psychology Community Based Interview Assignment

    ERIC Educational Resources Information Center

    White, Geoffry D.

    1977-01-01

    A course option in abnormal psychology involves students in interviewing and observing the activities of individuals in the off-campus community who are concerned with some aspect of abnormal psychology. The technique generates student interest in the field when they interview people about topics such as drug abuse, transsexualism, and abuse of…

  12. Detection of Structural Abnormalities Using Neural Nets

    NASA Technical Reports Server (NTRS)

    Zak, M.; Maccalla, A.; Daggumati, V.; Gulati, S.; Toomarian, N.

    1996-01-01

    This paper describes a feed-forward neural net approach for detection of abnormal system behavior based upon sensor data analyses. A new dynamical invariant representing structural parameters of the system is introduced in such a way that any structural abnormalities in the system behavior are detected from the corresponding changes to the invariant.

  13. Nail abnormalities in patients with vitiligo*

    PubMed Central

    Topal, Ilteris Oguz; Gungor, Sule; Kocaturk, Ozgur Emek; Duman, Hatice; Durmuscan, Mustafa

    2016-01-01

    Background Vitiligo is an acquired pigmentary skin disorder affecting 0.1-4% of the general population. The nails may be affected in patients with an autoimmune disease such as psoriasis, and in those with alopecia areata. It has been suggested that nail abnormalities should be apparent in vitiligo patients. Objective We sought to document the frequency and clinical presentation of nail abnormalities in vitiligo patients compared to healthy volunteers. We also examined the correlations between nail abnormalities and various clinical parameters. Methods This study included 100 vitiligo patients and 100 healthy subjects. Full medical histories were collected from the subjects, who underwent thorough general and nail examinations. All nail changes were noted. In the event of clinical suspicion of a fungal infection, additional mycological investigations were performed. Results Nail abnormalities were more prevalent in the patients (78%) than in the controls (55%) (p=0.001). Longitudinal ridging was the most common finding (42%), followed by (in descending order): leukonychia, an absent lunula, onycholysis, nail bed pallor, onychomycosis, splinter hemorrhage and nail plate thinning. The frequency of longitudinal ridging was significantly higher in patients than in controls (p<0.001). Conclusions Nail abnormalities were more prevalent in vitiligo patients than in controls. Systematic examination of the nails in such patients is useful because nail abnormalities are frequent. However, the causes of such abnormalities require further study. Longitudinal ridging and leukonychia were the most common abnormalities observed in this study. PMID:27579738

  14. Skeletal Muscle Abnormalities in Heart Failure.

    PubMed

    Kinugawa, Shintaro; Takada, Shingo; Matsushima, Shouji; Okita, Koichi; Tsutsui, Hiroyuki

    2015-01-01

    Exercise capacity is lowered in patients with heart failure, which limits their daily activities and also reduces their quality of life. Furthermore, lowered exercise capacity has been well demonstrated to be closely related to the severity and prognosis of heart failure. Skeletal muscle abnormalities including abnormal energy metabolism, transition of myofibers from type I to type II, mitochondrial dysfunction, reduction in muscular strength, and muscle atrophy have been shown to play a central role in lowered exercise capacity. The skeletal muscle abnormalities can be classified into the following main types: 1) low endurance due to mitochondrial dysfunction; and 2) low muscle mass and muscle strength due to imbalance of protein synthesis and degradation. The molecular mechanisms of these skeletal muscle abnormalities have been studied mainly using animal models. The current review including our recent study will focus upon the skeletal muscle abnormalities in heart failure. PMID:26346520

  15. Vascular tissue engineering: towards the next generation vascular grafts.

    PubMed

    Naito, Yuji; Shinoka, Toshiharu; Duncan, Daniel; Hibino, Narutoshi; Solomon, Daniel; Cleary, Muriel; Rathore, Animesh; Fein, Corey; Church, Spencer; Breuer, Christopher

    2011-04-30

    The application of tissue engineering technology to cardiovascular surgery holds great promise for improving outcomes in patients with cardiovascular diseases. Currently used synthetic vascular grafts have several limitations including thrombogenicity, increased risk of infection, and lack of growth potential. We have completed the first clinical trial evaluating the feasibility of using tissue engineered vascular grafts (TEVG) created by seeding autologous bone marrow-derived mononuclear cells (BM-MNC) onto biodegradable tubular scaffolds. Despite an excellent safety profile, data from the clinical trial suggest that the primary graft related complication of the TEVG is stenosis, affecting approximately 16% of grafts within the first seven years after implantation. Continued investigation into the cellular and molecular mechanisms underlying vascular neotissue formation will improve our basic understanding and provide insights that will enable the rationale design of second generation TEVG. PMID:21421015

  16. Vascular changes in hard palate sialolipoma: Sialoangiolipoma or vascular malformation?

    PubMed Central

    Handra-Luca, Adriana

    2015-01-01

    Palate sialolipomas are rare. Less than 10 cases located in the hard palate are reported to our knowledge. We report a case of hard palate sialolipoma, peculiar by the intratumor vascular patterns. A 67-year-old man presented with a 1.5 cm lesion of the oral hard palate. The lesion was surgically resected. On microscopy, the lesion, partly encapsulated, consisted of a proliferation of mature adipocytes containing normal minor salivary gland tissue and branching intratumoral vessels of varied size with irregularly thickened wall and papillary projections or tufts. The microscopic features of the tumor we report suggest that vascular malformation-like patterns may occur in sialolipomas of the hard palate. This morphological vascular peculiarity should be acknowledged since it may represent source of hemorrhage. PMID:26604516

  17. Identify potential drugs for cardiovascular diseases caused by stress-induced genes in vascular smooth muscle cells

    PubMed Central

    Ciou, Jin-Shuei; Chen, Shun-Tsung; Chung, Yi; Tsai, Jeffrey J. P.; Kurubanjerdjit, Nilubon

    2016-01-01

    Background Abnormal proliferation of vascular smooth muscle cells (VSMC) is a major cause of cardiovascular diseases (CVDs). Many studies suggest that vascular injury triggers VSMC dedifferentiation, which results in VSMC changes from a contractile to a synthetic phenotype; however, the underlying molecular mechanisms are still unclear. Methods In this study, we examined how VSMC responds under mechanical stress by using time-course microarray data. A three-phase study was proposed to investigate the stress-induced differentially expressed genes (DEGs) in VSMC. First, DEGs were identified by using the moderated t-statistics test. Second, more DEGs were inferred by using the Gaussian Graphical Model (GGM). Finally, the topological parameters-based method and cluster analysis approach were employed to predict the last batch of DEGs. To identify the potential drugs for vascular diseases involve VSMC proliferation, the drug-gene interaction database, Connectivity Map (cMap) was employed. Success of the predictions were determined using in-vitro data, i.e. MTT and clonogenic assay. Results Based on the differential expression calculation, at least 23 DEGs were found, and the findings were qualified by previous studies on VSMC. The results of gene set enrichment analysis indicated that the most often found enriched biological processes are cell-cycle-related processes. Furthermore, more stress-induced genes, well supported by literature, were found by applying graph theory to the gene association network (GAN). Finally, we showed that by processing the cMap input queries with a cluster algorithm, we achieved a substantial increase in the number of potential drugs with experimental IC50 measurements. With this novel approach, we have not only successfully identified the DEGs, but also improved the DEGs prediction by performing the topological and cluster analysis. Moreover, the findings are remarkably validated and in line with the literature. Furthermore, the cMap and

  18. MicroRNAs in vascular tissue engineering and post-ischemic neovascularization☆

    PubMed Central

    Caputo, Massimo; Saif, Jaimy; Rajakaruna, Cha; Brooks, Marcus; Angelini, Gianni D.; Emanueli, Costanza

    2015-01-01

    Increasing numbers of paediatric patients with congenital heart defects are surviving to adulthood, albeit with continuing clinical needs. Hence, there is still scope for revolutionary new strategies to correct vascular anatomical defects. Adult patients are also surviving longer with the adverse consequences of ischemic vascular disease, especially after acute coronary syndromes brought on by plaque erosion and rupture. Vascular tissue engineering and therapeutic angiogenesis provide new hope for these patients. Both approaches have shown promise in laboratory studies, but have not yet been able to deliver clear evidence of clinical success. More research into biomaterials, molecular medicine and cell and molecular therapies is necessary. This review article focuses on the new opportunities offered by targeting microRNAs for the improved production and greater empowerment of vascular cells for use in vascular tissue engineering or for increasing blood perfusion of ischemic tissues by amplifying the resident microvascular network. PMID:25980937

  19. Open Problems in Computational Vascular Biomechanics: Hemodynamics and Arterial Wall Mechanics

    PubMed Central

    Taylor, C.A.; Humphrey, J.D.

    2009-01-01

    The vasculature consists of a complex network of vessels ranging from large arteries to arterioles, capillaries, venules, and veins. This network is vital for the supply of oxygen and nutrients to tissues and the removal of carbon dioxide and waste products from tissues. Because of its primary role as a pressure-driven chemomechanical transport system, it should not be surprising that mechanics plays a vital role in the development and maintenance of the normal vasculature as well as in the progression and treatment of vascular disease. This review highlights some past successes of vascular biomechanics, but emphasizes the need for research that synthesizes complementary advances in molecular biology, biomechanics, medical imaging, computational methods, and computing power for purposes of increasing our understanding of vascular physiology and pathophysiology as well as improving the design of medical devices and clinical interventions, including surgical procedures. That is, computational mechanics has great promise to contribute to the continued improvement of vascular health. PMID:20161129

  20. Vascular effect of photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Fyodorov, Svyatoslav N.; Kopayeva, V. G.; Andreev, J. B.; Ponomarev, Gelii V.; Stranadko, Eugeny P.; Suchin, H. M.

    1996-01-01

    Vascular effect of PDT has been studied in patients with corneal vascularized leucomas (10 patients) and in patients with corneal neovascularized transplant (3 patients). For vascularized leucomas the method of photodynamic therapy consisted of the local injection of dimegin (deiteroporphyrin derivative) into the space of the newly-formed vessels under operating microscope (opton) with the microneedle (diameter 200 microns) and corneal irradiation by the operating microscope light. For corneal neovascularized transplant the injection of photogem (hematoporphyrin derivative) intravenously were made with subsequent irradiation by light of dye laser (5 hours after the injection) with light density of 150 mW/cm2 for 15 minutes. In all the cases at the time of irradiation the aggregated blood flow was appeared, followed by blood flow stasis. In postoperative period the vessels disintegrated into separate fragments which disappeared completely after 10 - 15 days. Taking into account the data of light microscopy, the disappearance of the vessels took place as a result of the vascular endothelium lisis along the vascular walls. Neovascularized cornea and newly-formed vessels in tumor stroms have much in common. The vessel alterations study presented in this paper, may serve to specify the mechanism of photodynamic destruction of neovascularized stroma of tumor.

  1. Vascular potassium channels in NVC.

    PubMed

    Yamada, K

    2016-01-01

    It has long been proposed that the external potassium ion ([K(+)]0) works as a potent vasodilator in the dynamic regulation of local cerebral blood flow. Astrocytes may play a central role for producing K(+) outflow possibly through calcium-activated potassium channels on the end feet, responding to a rise in the intracellular Ca(2+) concentration, which might well reflect local neuronal activity. A mild elevation of [K(+)]0 in the end feet/vascular smooth muscle space could activate Na(+)/K(+)-ATPase concomitant with inwardly rectifying potassium (Kir) channels in vascular smooth muscle cells, leading to a hyperpolarization of vascular smooth muscle and relaxation of smooth muscle actin-positive vessels. Also proposed notion is endothelial calcium-activated potassium channels and/or inwardly rectifying potassium channel-mediated hyperpolarization of vascular smooth muscle. A larger elevation of [K(+)]0, which may occur pathophysiologically in such as spreading depression or stroke, can trigger a depolarization of vascular smooth muscle cells and vasoconstriction instead. PMID:27130411

  2. Adverse Outcome Pathways for Embryonic Vascular Disruption and Alternative Methods to Identify Chemical Vascular Disruptor

    EPA Science Inventory

    Chemically induced vascular toxicity during embryonic development can result in a wide range of adverse prenatal outcomes. We used information from genetic mouse models linked to phenotypic outcomes and a vascular toxicity knowledge base to construct an embryonic vascular disrupt...

  3. The spacing principle for unlearning abnormal neuronal synchrony.

    PubMed

    Popovych, Oleksandr V; Xenakis, Markos N; Tass, Peter A

    2015-01-01

    Desynchronizing stimulation techniques were developed to specifically counteract abnormal neuronal synchronization relevant to several neurological and psychiatric disorders. The goal of our approach is to achieve an anti-kindling, where the affected neural networks unlearn abnormal synaptic connectivity and, hence, abnormal neuronal synchrony, by means of desynchronizing stimulation, in particular, Coordinated Reset (CR) stimulation. As known from neuroscience, psychology and education, learning effects can be enhanced by means of the spacing principle, i.e. by delivering repeated stimuli spaced by pauses as opposed to delivering a massed stimulus (in a single long stimulation session). To illustrate that the spacing principle may boost the anti-kindling effect of CR neuromodulation, in this computational study we carry this approach to extremes. To this end, we deliver spaced CR neuromodulation at particularly weak intensities which render permanently delivered CR neuromodulation ineffective. Intriguingly, spaced CR neuromodulation at these particularly weak intensities effectively induces an anti-kindling. In fact, the spacing principle enables the neuronal population to successively hop from one attractor to another one, finally approaching attractors characterized by down-regulated synaptic connectivity and synchrony. Our computational results might open up novel opportunities to effectively induce sustained desynchronization at particularly weak stimulation intensities, thereby avoiding side effects, e.g., in the case of deep brain stimulation.

  4. Theories of schizophrenia: a genetic-inflammatory-vascular synthesis

    PubMed Central

    Hanson, Daniel R; Gottesman, Irving I

    2005-01-01

    Background Schizophrenia, a relatively common psychiatric syndrome, affects virtually all brain functions yet has eluded explanation for more than 100 years. Whether by developmental and/or degenerative processes, abnormalities of neurons and their synaptic connections have been the recent focus of attention. However, our inability to fathom the pathophysiology of schizophrenia forces us to challenge our theoretical models and beliefs. A search for a more satisfying model to explain aspects of schizophrenia uncovers clues pointing to genetically mediated CNS microvascular inflammatory disease. Discussion A vascular component to a theory of schizophrenia posits that the physiologic abnormalities leading to illness involve disruption of the exquisitely precise regulation of the delivery of energy and oxygen required for normal brain function. The theory further proposes that abnormalities of CNS metabolism arise because genetically modulated inflammatory reactions damage the microvascular system of the brain in reaction to environmental agents, including infections, hypoxia, and physical trauma. Damage may accumulate with repeated exposure to triggering agents resulting in exacerbation and deterioration, or healing with their removal. There are clear examples of genetic polymorphisms in inflammatory regulators leading to exaggerated inflammatory responses. There is also ample evidence that inflammatory vascular disease of the brain can lead to psychosis, often waxing and waning, and exhibiting a fluctuating course, as seen in schizophrenia. Disturbances of CNS blood flow have repeatedly been observed in people with schizophrenia using old and new technologies. To account for the myriad of behavioral and other curious findings in schizophrenia such as minor physical anomalies, or reported decreased rates of rheumatoid arthritis and highly visible nail fold capillaries, we would have to evoke a process that is systemic such as the vascular and immune

  5. [Monitoring protocol of native vascular accesses for haemodialysis].

    PubMed

    Armada, E; Trillo, M; Pérez Melón, C; Molina Herrero, J; Gayoso, P; Camba, M; Morcillo Esteban, J; Otero, A

    2005-01-01

    Vascular access failure is an important cause of morbidity and mortality for patients on haemodialysis. We have prospectively studied, with a 5 years follow up, a monitoring protocol of native vascular accesses, using the available methods in every haemodialysis unit. All the native vascular accesses, created from 1- 1998 to XII-2001, with a posterior follow up until XII-2002, were monitored. Monitoring was based on physical examination, dificulty for blood flow greater than 300 ml/min, and in a monthly basis: dynamic venous pressure, urea recirculation and urea kinetic model. Abnormalities suggestive of fistulogram were a priori defined. During the recruitment period, a total of 164 accesses were created in 144 patients. Of these only 3 were grafts, 28 native vascular accesses were never functioning (primary failure rate 17. 1%), and 127 native accesses created in 113 patients (age 63.3 +/- 12.4 years; 18 % diabetics), were monitored (83% cephalic vein). Monitoring findings indicated realization of fistulogram in 35% and percutaneus angioplasty in 25% of the accesses. In order to maintain patency, the surgical intervention rate was 0.03 procedures/patient/year, the radiological 0.10 and the total 0.13. During the 5 years of the study occurred 41 thrombosis episodes in 40 accesses (0.07 thrombosis/patient/year), with percutaneus repermeabilization in 30%. Primary (unassisted) survival was 30.3 months (Confidence Interval 95% 25.6, 35.0) and secondary (assisted) survival 42.8 months (Confidence Interval 95%: 38.7, 46.9). Logistic regression analysis showed that presence of a central catheter at the time of creating the vascular access posses a greater risk for thrombosis (Relative Risk 5.6 if in subclavian vein), whereas age, diabetes, time to canulation, number of previous accesses and anatomic type do not increase that risk. In conclusion, in an old haemodialysis population, with an important diabetes prevalence, it is possible to create functioning native

  6. (123)I-FP-CIT SPECT imaging in early diagnosis of dementia in patients with and without a vascular component.

    PubMed

    Garriga, Marina; Milà, Marta; Mir, Manzoor; Al-Baradie, Raid; Huertas, Sonia; Castejon, Cesar; Casas, Laura; Badenes, Dolors; Giménez, Nuria; Font, M Angels; Gonzalez, Jose M; Ysamat, Maria; Aguilar, Miguel; Slevin, Mark; Krupinski, Jerzy

    2015-01-01

    Alzheimer's disease (AD) and vascular dementia (VaD) are the most common cause of dementia. Cerebral ischemia is a major risk factor for development of dementia. (123)I-FP-CIT SPECT (DaTScan) is a complementary tool in the differential diagnoses of patients with incomplete or uncertain Parkinsonism. Additional application of DaTScan enables the categorization of Parkinsonian disease with dementia (PDD), and its differentiation from pure AD, and may further contribute to change the therapeutic decision. The aim of this study was to analyze the vascular contribution towards dementia and mild cognitive impairment (MCI). We evaluated the utility of DaTScan for the early diagnosis of dementia in patients with and without a clinical vascular component, and the association between neuropsychological function, vascular component and dopaminergic function on DaTScan. One-hundred and five patients with MCI or the initial phases of dementia were studied prospectively. We developed an initial assessment using neurologic examination, blood tests, cognitive function tests, structural neuroimaging and DaTScan. The vascular component was later quantified in two ways: clinically, according to the Framingham Risk Score (FRS) and by structural neuroimaging using Wahlund Scale Total Score (WSTS). Early diagnosis of dementia was associated with an abnormal DaTScan. A significant association was found between a high WSTS and an abnormal DaTScan (p < 0.01). Mixed AD was the group with the highest vascular component, followed by the VaD group, while MCI and pure AD showed similar WSTS. No significant associations were found between neuropsychological impairment and DaTScan independently of associated vascular component. DaTScan seems to be a good tool to discriminate, in a first clinical assessment, patients with MCI from those with established dementia. There was bigger general vascular affectation observable in MRI or CT in patients with abnormal dopaminergic uptake seen on Da

  7. 123I-FP-CIT SPECT imaging in early diagnosis of dementia in patients with and without a vascular component

    PubMed Central

    Garriga, Marina; Milà, Marta; Mir, Manzoor; Al-Baradie, Raid; Huertas, Sonia; Castejon, Cesar; Casas, Laura; Badenes, Dolors; Giménez, Nuria; Font, M. Angels; Gonzalez, Jose M.; Ysamat, Maria; Aguilar, Miguel; Slevin, Mark; Krupinski, Jerzy

    2015-01-01

    Alzheimer’s disease (AD) and vascular dementia (VaD) are the most common cause of dementia. Cerebral ischemia is a major risk factor for development of dementia. 123I-FP-CIT SPECT (DaTScan) is a complementary tool in the differential diagnoses of patients with incomplete or uncertain Parkinsonism. Additional application of DaTScan enables the categorization of Parkinsonian disease with dementia (PDD), and its differentiation from pure AD, and may further contribute to change the therapeutic decision. The aim of this study was to analyze the vascular contribution towards dementia and mild cognitive impairment (MCI). We evaluated the utility of DaTScan for the early diagnosis of dementia in patients with and without a clinical vascular component, and the association between neuropsychological function, vascular component and dopaminergic function on DaTScan. One-hundred and five patients with MCI or the initial phases of dementia were studied prospectively. We developed an initial assessment using neurologic examination, blood tests, cognitive function tests, structural neuroimaging and DaTScan. The vascular component was later quantified in two ways: clinically, according to the Framingham Risk Score (FRS) and by structural neuroimaging using Wahlund Scale Total Score (WSTS). Early diagnosis of dementia was associated with an abnormal DaTScan. A significant association was found between a high WSTS and an abnormal DaTScan (p < 0.01). Mixed AD was the group with the highest vascular component, followed by the VaD group, while MCI and pure AD showed similar WSTS. No significant associations were found between neuropsychological impairment and DaTScan independently of associated vascular component. DaTScan seems to be a good tool to discriminate, in a first clinical assessment, patients with MCI from those with established dementia. There was bigger general vascular affectation observable in MRI or CT in patients with abnormal dopaminergic uptake seen on Da

  8. Intrapulmonary vascular remodeling: MSCT-based evaluation in COPD and alpha-1 antitrypsin deficient subjects

    NASA Astrophysics Data System (ADS)

    Crosnier, Adeline; Fetita, Catalin; Thabut, Gabriel; Brillet, Pierre-Yves

    2016-03-01

    Whether COPD is generally known as a small airway disease, recent investigations suggest that vascular remodeling could play a key role in disease progression. This paper develops a specific investigation framework in order to evaluate the remodeling of the intrapulmonary vascular network and its correlation with other image or clinical parameters (emphysema score or FEV1) in patients with smoking- or genetic- (alpha-1 antitrypsin deficiency - AATD) related COPD. The developed approach evaluates the vessel caliber distribution per lung or lung region (upper, lower, 10%- and 20%- periphery) in relation with the severity of the disease and computes a remodeling marker given by the area under the caliber distribution curve for radii less than 1.6mm, AUC16. It exploits a medial axis analysis in relation with local caliber information computed in the segmented vascular network, with values normalized with respect to the lung volume (for which a robust segmentation is developed). The first results obtained on a 34-patient database (13 COPD, 13 AATD and 8 controls) showed significant vascular remodeling for COPD and AATD versus controls, with a negative correlation with the emphysema degree for COPD, but not for AATD. Significant vascular remodeling at 20% lung periphery was found both for the severe COPD and AATD patients, but not for the moderate groups. Also the vascular remodeling in AATD did not correlate with the FEV1, nor with DLCO, which might suggest independent mechanisms for bronchial and vascular remodeling in the lung.

  9. Vascular ultrasound for atherosclerosis imaging

    PubMed Central

    de Korte, Chris L.; Hansen, Hendrik H. G.; van der Steen, Anton F. W.

    2011-01-01

    Cardiovascular disease is a leading cause of death in the Western world. Therefore, detection and quantification of atherosclerotic disease is of paramount importance to monitor treatment and possible prevention of acute events. Vascular ultrasound is an excellent technique to assess the geometry of vessel walls and plaques. The high temporal as well as spatial resolution allows quantification of luminal area and plaque size and volume. While carotid arteries can be imaged non-invasively, scanning of coronary arteries requires invasive intravascular catheters. Both techniques have already demonstrated their clinical applicability. Using linear array technology, detection of disease as well as monitoring of pharmaceutical treatment in carotid arteries are feasible. Data acquired with intravascular ultrasound catheters have proved to be especially beneficial in understanding the development of atherosclerotic disease in coronary arteries. With the introduction of vascular elastography not only the geometry of plaques but also the risk for rupture of plaques might be identified. These so-called vulnerable plaques are frequently not flow-limiting and rupture of these plaques is responsible for the majority of cerebral and cardiac ischaemic events. Intravascular ultrasound elastography studies have demonstrated a high correlation between high strain and vulnerable plaque features, both ex vivo and in vivo. Additionally, pharmaceutical intervention could be monitored using this technique. Non-invasive vascular elastography has recently been developed for carotid applications by using compound scanning. Validation and initial clinical evaluation is currently being performed. Since abundance of vasa vasorum (VV) is correlated with vulnerable plaque development, quantification of VV might be a unique tool to even prevent this from happening. Using ultrasound contrast agents, it has been demonstrated that VV can be identified and quantified. Although far from routine

  10. Treatment of children with pulmonary hypertension. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK.

    PubMed

    Hansmann, Georg; Apitz, Christian

    2016-05-01

    Treatment of children and adults with pulmonary hypertension (PH) with or without cardiac dysfunction has improved in the last two decades. The so-called pulmonary arterial hypertension (PAH)-specific medications currently approved for therapy of adults with PAH target three major pathways (endothelin, nitric oxide, prostacyclin). Moreover, some PH centres may use off-label drugs for compassionate use. Pulmonary hypertensive vascular disease (PHVD) in children is complex, and selection of appropriate therapies remains difficult. In addition, paediatric PAH/PHVD therapy is vastly based on experience and trial data from adult rather than paediatric studies; however, the first randomised paediatric PAH trials have been conducted recently. We present consensus recommendations for the treatment of children with PH. Class of recommendation and level of evidence were assigned based on paediatric data only or on adult studies that included >10% children. After a systematic literature search and analysis of the published data, we developed treatment strategies and algorithms that can guide goal-oriented PH therapy. We discuss early combination therapy (double, triple) in patients with PAH in functional class II-IV and in those with inadequate response to the initial pharmacotherapy. In those children with progressive, severe PAH and inadequate response, advances in drug development, and interventional and surgical approaches provide promising new strategies to avoid, reverse or ameliorate right heart failure and left ventricular compression. In particular, first follow-up data indicate that Potts shunt (left pulmonary artery to descending aorta anastomosis) may be an alternative destination therapy, or bridge to bilateral lung transplantation, in end-stage paediatric PAH. PMID:27053700

  11. Treatment of children with pulmonary hypertension. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK.

    PubMed

    Hansmann, Georg; Apitz, Christian

    2016-05-01

    Treatment of children and adults with pulmonary hypertension (PH) with or without cardiac dysfunction has improved in the last two decades. The so-called pulmonary arterial hypertension (PAH)-specific medications currently approved for therapy of adults with PAH target three major pathways (endothelin, nitric oxide, prostacyclin). Moreover, some PH centres may use off-label drugs for compassionate use. Pulmonary hypertensive vascular disease (PHVD) in children is complex, and selection of appropriate therapies remains difficult. In addition, paediatric PAH/PHVD therapy is vastly based on experience and trial data from adult rather than paediatric studies; however, the first randomised paediatric PAH trials have been conducted recently. We present consensus recommendations for the treatment of children with PH. Class of recommendation and level of evidence were assigned based on paediatric data only or on adult studies that included >10% children. After a systematic literature search and analysis of the published data, we developed treatment strategies and algorithms that can guide goal-oriented PH therapy. We discuss early combination therapy (double, triple) in patients with PAH in functional class II-IV and in those with inadequate response to the initial pharmacotherapy. In those children with progressive, severe PAH and inadequate response, advances in drug development, and interventional and surgical approaches provide promising new strategies to avoid, reverse or ameliorate right heart failure and left ventricular compression. In particular, first follow-up data indicate that Potts shunt (left pulmonary artery to descending aorta anastomosis) may be an alternative destination therapy, or bridge to bilateral lung transplantation, in end-stage paediatric PAH.

  12. [Vascular Calcification - Pathological Mechanism and Clinical Application - . Role of vascular smooth muscle cells in vascular calcification].

    PubMed

    Kurabayashi, Masahiko

    2015-05-01

    Vascular calcification is commonly seen with aging, chronic kidney disese (CKD), diabetes, and atherosclerosis, and is closely associated with cardiovascular morbidity and mortality. Vascular calcification has long been regarded as the final stage of degeneration and necrosis of arterial wall and a passive, unregulated process. However, it is now known to be an active and tightly regulated process involved with phenotypic transition of vascular smooth muscle cells (VSMC) that resembles bone mineralization. Briefly, calcium deposits of atherosclerotic plaque consist of hydroxyapatite and may appear identical to fully formed lamellar bone. By using a genetic fate mapping strategy, VSMC of the vascular media give rise to the majority of the osteochondrogenic precursor- and chondrocyte-like cells observed in the calcified arterial media of MGP (- / -) mice. Osteogenic differentiation of VSMC is characterized by the expression of bone-related molecules including bone morphogenetic protein (BMP) -2, Msx2 and osteopontin, which are produced by osteoblasts and chondrocytes. Our recent findings are that (i) Runx2 and Notch1 induce osteogenic differentiation, and (ii) advanced glycation end-product (AGE) /receptor for AGE (RAGE) and palmitic acid promote osteogenic differentiation of VSMC. To understand of the molecular mechanisms of vascular calcification is now under intensive research area. PMID:25926569

  13. [Vascular Calcification - Pathological Mechanism and Clinical Application - . Role of vascular smooth muscle cells in vascular calcification].

    PubMed

    Kurabayashi, Masahiko

    2015-05-01

    Vascular calcification is commonly seen with aging, chronic kidney disese (CKD), diabetes, and atherosclerosis, and is closely associated with cardiovascular morbidity and mortality. Vascular calcification has long been regarded as the final stage of degeneration and necrosis of arterial wall and a passive, unregulated process. However, it is now known to be an active and tightly regulated process involved with phenotypic transition of vascular smooth muscle cells (VSMC) that resembles bone mineralization. Briefly, calcium deposits of atherosclerotic plaque consist of hydroxyapatite and may appear identical to fully formed lamellar bone. By using a genetic fate mapping strategy, VSMC of the vascular media give rise to the majority of the osteochondrogenic precursor- and chondrocyte-like cells observed in the calcified arterial media of MGP (- / -) mice. Osteogenic differentiation of VSMC is characterized by the expression of bone-related molecules including bone morphogenetic protein (BMP) -2, Msx2 and osteopontin, which are produced by osteoblasts and chondrocytes. Our recent findings are that (i) Runx2 and Notch1 induce osteogenic differentiation, and (ii) advanced glycation end-product (AGE) /receptor for AGE (RAGE) and palmitic acid promote osteogenic differentiation of VSMC. To understand of the molecular mechanisms of vascular calcification is now under intensive research area.

  14. Vascular contributions to cognitive impairment

    PubMed Central

    Flores, Alan

    2015-01-01

    Summary Unlike many neurodegenerative causes of cognitive impairment and dementia, vascular damage is preventable. Despite the heterogeneity of vascular cognitive impairment (VCI) and the complexity of its clinical presentations, the potential for limiting progression and changing the trajectory of damage makes it all the more important for physicians to be educated about the syndrome and to remain vigilant when taking care of patients. In this review, we outline an approach to patients with possible VCI, summarize current treatment and prevention guidelines, and provide an overview with case examples. PMID:26124978

  15. Genetic basis for vascular anomalies.

    PubMed

    Kirkorian, A Yasmine; Grossberg, Anna L; Püttgen, Katherine B

    2016-03-01

    The fundamental genetics of many isolated vascular anomalies and syndromes associated with vascular anomalies have been elucidated. The rate of discovery continues to increase, expanding our understanding of the underlying interconnected molecular pathways. This review summarizes genetic and clinical information on the following diagnoses: capillary malformation, venous malformation, lymphatic malformation, art