Sample records for accelerate thrombus formation

  1. Vibration assessment for thrombus formation in the centrifugal pump.

    PubMed

    Nakazawa, T; Makinouchi, K; Takami, Y; Glueck, J; Tayama, E; Nosé, Y

    1997-04-01

    To clarify the correlation of vibration and thrombus formation inside a rotary blood pump, 40 preliminary vibration studies were performed on pivot bearing centrifugal pumps. No such studies were found in the literature. The primary data acquisition equipment included an accelerometer (Isotron PE accelerometer, ENDEVCO, San Juan Capistrano, CA, U.S.A.), digitizing oscilloscope (TDS 420, Tektronix Inc., Pittsfield, MA, U.S.A.), and pivot bearing centrifugal pumps. The pump impeller was coupled magnetically to the driver magnet. The accelerometer was mounted on the top of the pump casing to sense radial and axial accelerations. To simulate the 3 common areas of thrombus formation, a piece of silicone rubber was attached to each of the following 3 locations as described: a circular shape on the center bottom of the impeller (CI), an eccentric shape on the bottom of the impeller (EI), and a circular shape on the center bottom casing (CC). A fast Fourier transform (FFT) method at 5 L/min against 100 mm Hg, with a pump rotating speed of 1,600 rpm was used. The frequency response of the vibration sensors used spans of 40 Hz to 2 kHz. The frequency domain was already integrated into the oscilloscope, allowing for comparison of the vibration results. The area of frequency domain at a radial direction was 206 +/- 12.7 mVHz in CI, 239.5 +/- 12.1 mVHz in EI, 365 +/- 12.9 mVHz in CC, and 163 +/- 7.9 mVHz in the control (control vs. CI p = 0.07, control vs. EI p < 0.001, control vs. CC p < 0.001, EI vs. CC p < 0.001, CI vs. CC p < 0.001). Three types of imitation thrombus formations were roughly distinguishable. These results suggested the possibility of detecting thrombus formation using vibration signals, and these studies revealed the usefulness of vibration monitoring to detect thrombus formation in a centrifugal pump.

  2. Platelet response heterogeneity in thrombus formation.

    PubMed

    Munnix, Imke C A; Cosemans, Judith M E M; Auger, Jocelyn M; Heemskerk, Johan W M

    2009-12-01

    Vascular injury leads to formation of a structured thrombus as a consequence of platelet activation and aggregation, thrombin and fibrin formation, and trapping of leukocytes and red cells. This review summarises current evidence for heterogeneity of platelet responses and functions in the thrombus-forming process. Environmental factors contribute to response heterogeneity, as the platelets in a thrombus adhere to different substrates, and sense specific (ant)agonists and rheological conditions. Contraction of platelets and interaction with fibrin and other blood cells cause further response variation. On the other hand, response heterogeneity can also be due to intrinsic differences between platelets in age and in receptor and signalling proteins. As a result, at least three subpopulations of platelets are formed in a thrombus: aggregating platelets with (reversible) integrin activation, procoagulant (coated) platelets exposing phosphatidylserine and binding coagulation factors, and contracting platelets with cell-cell contacts. This recognition of thrombus heterogeneity has implications for the use and development of antiplatelet medication.

  3. Thrombus Formation at High Shear Rates.

    PubMed

    Casa, Lauren D C; Ku, David N

    2017-06-21

    The final common pathway in myocardial infarction and ischemic stroke is occlusion of blood flow from a thrombus forming under high shear rates in arteries. A high-shear thrombus forms rapidly and is distinct from the slow formation of coagulation that occurs in stagnant blood. Thrombosis at high shear rates depends primarily on the long protein von Willebrand factor (vWF) and platelets, with hemodynamics playing an important role in each stage of thrombus formation, including vWF binding, platelet adhesion, platelet activation, and rapid thrombus growth. The prediction of high-shear thrombosis is a major area of biofluid mechanics in which point-of-care testing and computational modeling are promising future directions for clinically relevant research. Further research in this area will enable identification of patients at high risk for arterial thrombosis, improve prevention and treatment based on shear-dependent biological mechanisms, and improve blood-contacting device design to reduce thrombosis risk.

  4. PKCalpha regulates platelet granule secretion and thrombus formation in mice.

    PubMed

    Konopatskaya, Olga; Gilio, Karen; Harper, Matthew T; Zhao, Yan; Cosemans, Judith M E M; Karim, Zubair A; Whiteheart, Sidney W; Molkentin, Jeffery D; Verkade, Paul; Watson, Steve P; Heemskerk, Johan W M; Poole, Alastair W

    2009-02-01

    Platelets are central players in atherothrombosis development in coronary artery disease. The PKC family provides important intracellular mechanisms for regulating platelet activity, and platelets express several members of this family, including the classical isoforms PKCalpha and PKCbeta and novel isoforms PKCdelta and PKCtheta. Here, we used a genetic approach to definitively demonstrate the role played by PKCalpha in regulating thrombus formation and platelet function. Thrombus formation in vivo was attenuated in Prkca-/- mice, and PKCalpha was required for thrombus formation in vitro, although this PKC isoform did not regulate platelet adhesion to collagen. The ablation of in vitro thrombus formation in Prkca-/- platelets was rescued by the addition of ADP, consistent with the key mechanistic finding that dense-granule biogenesis and secretion depend upon PKCalpha expression. Furthermore, defective platelet aggregation in response to either collagen-related peptide or thrombin could be overcome by an increase in agonist concentration. Evidence of overt bleeding, including gastrointestinal and tail bleeding, was not seen in Prkca-/- mice. In summary, the effects of PKCalpha ablation on thrombus formation and granule secretion may implicate PKCalpha as a drug target for antithrombotic therapy.

  5. Platelet size and density affect shear-induced thrombus formation in tortuous arterioles

    NASA Astrophysics Data System (ADS)

    Chesnutt, Jennifer K. W.; Han, Hai-Chao

    2013-10-01

    Thrombosis accounts for 80% of deaths in patients with diabetes mellitus. Diabetic patients demonstrate tortuous microvessels and larger than normal platelets. Large platelets are associated with increased platelet activation and thrombosis, but the physical effects of large platelets in the microscale processes of thrombus formation are not clear. Therefore, the objective of this study was to determine the physical effects of mean platelet volume (MPV), mean platelet density (MPD) and vessel tortuosity on platelet activation and thrombus formation in tortuous arterioles. A computational model of the transport, shear-induced activation, collision, adhesion and aggregation of individual platelets was used to simulate platelet interactions and thrombus formation in tortuous arterioles. Our results showed that an increase in MPV resulted in a larger number of activated platelets, though MPD and level of tortuosity made little difference on platelet activation. Platelets with normal MPD yielded the lowest amount of mural thrombus. With platelets of normal MPD, the amount of mural thrombus decreased with increasing level of tortuosity but did not have a simple monotonic relationship with MPV. The physical mechanisms associated with MPV, MPD and arteriole tortuosity play important roles in platelet activation and thrombus formation.

  6. Inhibition of thrombus formation on intravascular sensors by electrical polarization.

    PubMed

    Schmitt, J M; Baer, M; Meindl, J D; Anderson, M F; Mihm, F G

    1984-09-01

    Implantable biomedical sensors built on a silicon substrate capped with glass are currently being developed for intravascular applications. Electrical techniques for inhibiting thrombus formation on the surface of a proposed optical sensor in direct contact with blood have been investigated. Glass-on-silicon specimens (4 X 1.2 X 0.4 mm3) were coated with indium-tin oxide, a transparent conductor, and implanted in the vena cava and iliac veins of three dogs for 10, 20, or 33 days. The equilibrium surface-blood interface potentials of the specimens were modified by implanted current sources which supplied either direct current (8-15 microA) or 100 KHz alternating current (5 microA, root mean square). Light-microscopic and scanning electron-microscopic analyses showed each of the DC-polarized specimens to be free of thrombus, in contrast to nonpolarized (control) specimens on which varying amounts of adsorbed protein and thrombus deposits were found. Like the control specimens, the AC-polarized specimens formed thrombus, but the appearance of the deposits differed. These findings support the view that the polarity, magnitude and time dependence of the potential across conducting surface-blood interface significantly influence thrombogenicity. Further work is necessary to determine the roles of electrochemical and electrostatic factors in preventing thrombus formation on foreign materials.

  7. Feasibility of the optical imaging of thrombus formation in a rotary blood pump by near-infrared light.

    PubMed

    Sakota, Daisuke; Murashige, Tomotaka; Kosaka, Ryo; Nishida, Masahiro; Maruyama, Osamu

    2014-09-01

    Blood coagulation is one of the primary concerns when using mechanical circulatory support devices such as blood pumps. Noninvasive detection and imaging of thrombus formation is useful not only for the development of more hemocompatible devices but also for the management of blood coagulation to avoid risk of infarction. The objective of this study is to investigate the use of near-infrared light for imaging of thrombus formation in a rotary blood pump. The optical properties of a thrombus at wavelengths ranging from 600 to 750 nm were analyzed using a hyperspectral imaging (HSI) system. A specially designed hydrodynamically levitated centrifugal blood pump with a visible bottom area was used. In vitro antithrombogenic testing was conducted five times with the pump using bovine whole blood in which the activated blood clotting time was adjusted to 200 s prior to the experiment. Two halogen lights were used for the light sources. The forward scattering through the pump and backward scattering on the pump bottom area were imaged using the HSI system. HSI showed an increase in forward scattering at wavelengths ranging from 670 to 750 nm in the location of thrombus formation. The time at which the thrombus began to form in the impeller rotating at 2780 rpm could be detected. The spectral difference between the whole blood and the thrombus was utilized to image thrombus formation. The results indicate the feasibility of dynamically detecting and imaging thrombus formation in a rotary blood pump. Copyright © 2014 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  8. Enhanced Venous Thrombus Resolution in Plasminogen Activator Inhibitor Type-2 Deficient Mice

    PubMed Central

    Siefert, Suzanne A; Chabasse, Christine; Mukhopadhyay, Subhradip; Hoofnagle, Mark H; Strickland, Dudley K; Sarkar, Rajabrata; Antalis, Toni M

    2014-01-01

    Background The resolution of deep vein thrombosis (DVT) requires an inflammatory response and mobilization of proteases, such as urokinase-type plasminogen activator (uPA) and matrix metalloproteinases (MMPs), to degrade the thrombus and remodel the injured vein wall. PAI-2 is a serine protease inhibitor (serpin) with unique immunosuppressive and cell survival properties that was originally identified as an inhibitor of uPA. Objective To investigate the role of PAI-2 in venous thrombus formation and resolution. Methods Venous thrombus resolution was compared in wild type C57BL/6, PAI-2 -/- and PAI-1 -/- mice using the stasis model of DVT. Formed thrombi were harvested, thrombus weights were recorded, and tissue was analyzed for uPA, and MMP activities, PAI-1 expression, and the nature of inflammatory cell infiltration. Results We found that absence of PAI-2 enhanced venous thrombus resolution, while thrombus formation was unaffected. Enhanced venous thrombus resolution in PAI-2 -/- mice was associated with increased uPA activity and reduced levels of PAI-1, with no significant effect on MMP-2 and -9 activities. PAI-1 deficiency resulted in an increase in thrombus resolution similar to PAI-2 deficiency, but additionally reduced venous thrombus formation and altered MMP activity. PAI-2 deficient thrombi had increased levels of the neutrophil chemoattractant, CXCL2, which was associated with early enhanced neutrophil recruitment. Conclusions These data identify PAI-2 as a novel regulator of venous thrombus resolution, which modulates several pathways involving both inflammatory and uPA activity mechanisms, distinct from PAI-1. Further examination of these pathways may lead to potential therapeutic prospects in accelerating thrombus resolution. PMID:25041188

  9. Enhanced venous thrombus resolution in plasminogen activator inhibitor type-2 deficient mice.

    PubMed

    Siefert, S A; Chabasse, C; Mukhopadhyay, S; Hoofnagle, M H; Strickland, D K; Sarkar, R; Antalis, T M

    2014-10-01

    The resolution of deep vein thrombosis requires an inflammatory response and mobilization of proteases, such as urokinase-type plasminogen activator (uPA) and matrix metalloproteinases (MMPs), to degrade the thrombus and remodel the injured vein wall. Plasminogen activator inhibitor type 2 (PAI-2) is a serine protease inhibitor (serpin) with unique immunosuppressive and cell survival properties that was originally identified as an inhibitor of uPA. To investigate the role of PAI-2 in venous thrombus formation and resolution. Venous thrombus resolution was compared in wild-type C57BL/6, PAI-2(-/-) , and PAI-1(-/-) mice using the stasis model of deep vein thrombosis. Formed thrombi were harvested, thrombus weights were recorded, and tissue was analyzed for uPA and MMP activities, PAI-1 expression, and the nature of inflammatory cell infiltration. We found that the absence of PAI-2 enhanced venous thrombus resolution, while thrombus formation was unaffected. Enhanced venous thrombus resolution in PAI-2(-/-) mice was associated with increased uPA activity and reduced levels of PAI-1, with no significant effect on MMP-2 and -9 activities. PAI-1 deficiency resulted in an increase in thrombus resolution similar to PAI-2 deficiency, but additionally reduced venous thrombus formation and altered MMP activity. PAI-2-deficient thrombi had increased levels of the neutrophil chemoattractant CXCL2, which was associated with early enhanced neutrophil recruitment. These data identify PAI-2 as a novel regulator of venous thrombus resolution, which modulates several pathways involving both inflammatory and uPA activity mechanisms, distinct from PAI-1. Further examination of these pathways may lead to potential therapeutic prospects in accelerating thrombus resolution. © 2014 International Society on Thrombosis and Haemostasis.

  10. Computational Study of Thrombus Formation and Clotting Factor Effects under Venous Flow Conditions

    PubMed Central

    Govindarajan, Vijay; Rakesh, Vineet; Reifman, Jaques; Mitrophanov, Alexander Y.

    2016-01-01

    A comprehensive understanding of thrombus formation as a physicochemical process that has evolved to protect the integrity of the human vasculature is critical to our ability to predict and control pathological states caused by a malfunctioning blood coagulation system. Despite numerous investigations, the spatial and temporal details of thrombus growth as a multicomponent process are not fully understood. Here, we used computational modeling to investigate the temporal changes in the spatial distributions of the key enzymatic (i.e., thrombin) and structural (i.e., platelets and fibrin) components within a growing thrombus. Moreover, we investigated the interplay between clot structure and its mechanical properties, such as hydraulic resistance to flow. Our model relied on the coupling of computational fluid dynamics and biochemical kinetics, and was validated using flow-chamber data from a previous experimental study. The model allowed us to identify the distinct patterns characterizing the spatial distributions of thrombin, platelets, and fibrin accumulating within a thrombus. Our modeling results suggested that under the simulated conditions, thrombin kinetics was determined predominantly by prothrombinase. Furthermore, our simulations showed that thrombus resistance imparted by fibrin was ∼30-fold higher than that imparted by platelets. Yet, thrombus-mediated bloodflow occlusion was driven primarily by the platelet deposition process, because the height of the platelet accumulation domain was approximately twice that of the fibrin accumulation domain. Fibrinogen supplementation in normal blood resulted in a nonlinear increase in thrombus resistance, and for a supplemented fibrinogen level of 48%, the thrombus resistance increased by ∼2.7-fold. Finally, our model predicted that restoring the normal levels of clotting factors II, IX, and X while simultaneously restoring fibrinogen (to 88% of its normal level) in diluted blood can restore fibrin generation to

  11. A Computational Model for Thrombus Formation in Response to Cardiovascular Implantable Devices

    NASA Astrophysics Data System (ADS)

    Horn, John; Ortega, Jason; Maitland, Duncan

    2014-11-01

    Cardiovascular implantable devices elicit complex physiological responses within blood. Notably, alterations in blood flow dynamics and interactions between blood proteins and biomaterial surface chemistry may lead to the formation of thrombus. For some devices, such as stents and heart valves, this is an adverse outcome. For other devices, such as embolic aneurysm treatments, efficient blood clot formation is desired. Thus a method to study how biomedical devices induce thrombosis is paramount to device development and optimization. A multiscale, multiphysics computational model is developed to predict thrombus formation within the vasculature. The model consists of a set of convection-diffusion-reaction partial differential equations for blood protein constituents involved in the progression of the clotting cascades. This model is used to study thrombus production from endovascular devices with the goal of optimizing the device design to generate the desired clotting response. This work was performed in part under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

  12. Elevated plasma factor VIII enhances venous thrombus formation in rabbits: contribution of factor XI, von Willebrand factor and tissue factor.

    PubMed

    Sugita, Chihiro; Yamashita, Atsushi; Matsuura, Yunosuke; Iwakiri, Takashi; Okuyama, Nozomi; Matsuda, Shuntaro; Matsumoto, Tomoko; Inoue, Osamu; Harada, Aya; Kitazawa, Takehisa; Hattori, Kunihiro; Shima, Midori; Asada, Yujiro

    2013-07-01

    Elevated plasma levels of factor VIII (FVIII) are associated with increased risk of deep venous thrombosis. The aim of this study is to elucidate how elevated FVIII levels affect venous thrombus formation and propagation in vivo. We examined rabbit plasma FVIII activity, plasma thrombin generation, whole blood coagulation, platelet aggregation and venous wall thrombogenicity before and one hour after an intravenous infusion of recombinant human FVIII (rFVIII). Venous thrombus induced by the endothelial denudation of rabbit jugular veins was histologically assessed. Thrombus propagation was evaluated as indocyanine green fluorescence intensity. Argatroban, a thrombin inhibitor, and neutralised antibodies for tissue factor (TF), factor XI (FXI), and von Willebrand factor (VWF) were infused before or after thrombus induction to investigate their effects on venous thrombus formation or propagation. Recombinant FVIII (100 IU/kg) increased rabbit plasma FVIII activity two-fold and significantly enhanced whole blood coagulation and total plasma thrombin generation, but did not affect initial thrombin generation time, platelet aggregation and venous wall thrombogenicity. The rFVIII infusion also increased the size of venous thrombus 1 hour after thrombus induction. Argatroban and the antibodies for TF, FXI or VWF inhibited such enhanced thrombus formation and all except TF suppressed thrombus propagation. In conclusion, elevated plasma FVIII levels enhance venous thrombus formation and propagation. Excess thrombin generation by FXI and VWF-mediated FVIII recruitment appear to contribute to the growth of FVIII-driven venous thrombus.

  13. Deep vein thrombus formation induced by flow reduction in mice is determined by venous side branches.

    PubMed

    Brandt, Moritz; Schönfelder, Tanja; Schwenk, Melanie; Becker, Christian; Jäckel, Sven; Reinhardt, Christoph; Stark, Konstantin; Massberg, Steffen; Münzel, Thomas; von Brühl, Marie-Luise; Wenzel, Philip

    2014-01-01

    Interaction between vascular wall abnormalities, inflammatory leukocytes, platelets, coagulation factors and hemorheology in the pathogenesis of deep vein thrombosis (DVT) is incompletely understood, requiring well defined animal models of human disease. We subjected male C57BL/6 mice to ligation of the inferior vena cava (IVC) as a flow reduction model to induce DVT. Thrombus size and weight were analyzed macroscopically and sonographically by B-mode, pulse wave (pw) Doppler and power Doppler imaging (PDI) using high frequency ultrasound. Thrombus size varied substantially between individual procedures and mice, irrespective of the flow reduction achieved by the ligature. Interestingly, PDI accurately predicted thrombus size in a very robust fashion (r2 = 0.9734, p < 0.0001). Distance of the insertion of side branches from the ligature significantly determines thrombus weight (r2 = 0.5597, p < 0.0001) and length (r2 = 0.5441, p < 0.0001) in the IVC, regardless of the flow measured by pw-Doppler with distances <1.5 mm drastically impairing thrombus formation. Occlusion of side branches prior to ligation of IVC did not increase thrombus size, probably due to patent side branches inaccessible to surgery. Venous side branches influence thrombus size in experimental DVT and might therefore prevent thrombus formation. This renders vessel anatomy and hemorheology important determinants in mouse models of DVT, which should be controlled for.

  14. The fluid mechanics of thrombus formation

    NASA Technical Reports Server (NTRS)

    1972-01-01

    Experimental data are presented for the growth of thrombi (blood clots) in a stagnation point flow of fresh blood. Thrombus shape, size and structure are shown to depend on local flow conditions. The evolution of a thrombus is described in terms of a physical model that includes platelet diffusion, a platelet aggregation mechanism, and diffusion and convection of the chemical species responsible for aggregation. Diffusion-controlled and convection-controlled regimes are defined by flow parameters and thrombus location, and the characteristic growth pattern in each regime is explained. Quantitative comparisons with an approximate theoretical model are presented, and a more general model is formulated.

  15. Defective PDI release from platelets and endothelial cells impairs thrombus formation in Hermansky-Pudlak syndrome

    PubMed Central

    Sharda, Anish; Kim, Sarah H.; Jasuja, Reema; Gopal, Srila; Flaumenhaft, Robert; Furie, Barbara C.

    2015-01-01

    Protein disulfide isomerase (PDI), secreted from platelets and endothelial cells after injury, is required for thrombus formation. The effect of platelet and endothelial cell granule contents on PDI-mediated thrombus formation was studied by intravital microscopy using a mouse model of Hermansky-Pudlak syndrome in which platelet dense granules are absent. Platelet deposition and fibrin generation were nearly absent, and extracellular PDI was significantly reduced in HPS6−/− mice after vascular injury. HPS6−/− platelets displayed impaired PDI secretion and impaired exocytosis of α granules, lysosomes, and T granules due to decreased sensitivity to thrombin, but these defects could be corrected by addition of subthreshold amounts of adenosine 5′-diphosphate (ADP). Human Hermansky-Pudlak syndrome platelets demonstrated similar characteristics. Infusion of wild-type platelets rescued thrombus formation in HPS6−/− mice. Human umbilical vein endothelial cells in which the HPS6 gene was silenced displayed impaired PDI secretion and exocytosis of Weibel-Palade bodies. Defective thrombus formation in Hermansky-Pudlak syndrome, associated with impaired exocytosis of residual granules in endothelial cells and platelets, the latter due to deficiency of ADP, is characterized by a defect in T granule secretion, a deficiency in extracellular PDI secretion, and impaired fibrin generation and platelet aggregation. Hermansky-Pudlak syndrome is an example of a hereditary disease whereby impaired PDI secretion contributes to a bleeding phenotype. PMID:25593336

  16. Comparison Between Retrograde and Antegrade Peripheral Venous Cannulation in Intensive Care Unit Patients: Assessment of Thrombus Formation.

    PubMed

    Abdelaal Ahmed Mahmoud, Ahmed; El-Shafei, Hassan Ismail; Yassin, Hany Mahmoud; Elramely, Mohamed Adly; Abdelhaq, Mohamed Mohamed; El Kady, Hany Wafiq; Awada, Wael Nabil Fahemy

    2017-06-01

    Antegrade cannulation of peripheral veins is the usual practice. Blood stasis between a catheter and the wall of the vein or at its tip in addition to catheter-induced phlebitis may initiate a thrombosis. The use of retrograde ventriculojugular shunts against the direction of the blood flow with resultant decrease in the incidence of venous thrombosis encouraged us to compare retrograde versus conventional antegrade peripheral venous cannulation. Monocentric, nonblinded, prospective observational cohort of 40 intensive care unit patients receiving 2 peripheral venous catheters in upper limbs, 1 inserted in the direction of blood flow (antegrade cannula) and the other inserted in an opposite direction to blood flow (retrograde cannula). Daily ultrasound assessment of the angle between the catheter and the vascular wall was done to detect onset and progression of thrombus formation. The study included 40 patients, aged 46.7 ± 10.132 years. The incidence of thrombus formation was 100% in both techniques. The onset time of thrombus formation between the catheter and the wall of a vein was significantly longer with the retrograde catheters than with the antegrade catheters with median time (interquartile range [range]) 6 days (5-6.75 [4-8]) with 95% confidence interval (CI), 5.58-6.42 vs 3 days (3-4 [2-5]) with 95% CI (2.76-3.24), respectively, with a P value <.001. The time needed by the recently detected thrombus to reach the catheter tip determined by ultrasound with or without catheter failure was significantly longer in the retrograde catheters than in the antegrade catheter with median time (interquartile range [range]) 9 days (8-9 [7-10]) with 95% CI, 8.76-9.24 vs 4 days (4-5 [3-6]) with 95% CI, 3.76-4.24, respectively, with a P value <.001. Retrograde cannulation did not decrease the incidence of thrombus formation, but significantly increased the onset time until thrombus formation and prolonged the time needed by the newly formed thrombus to reach the

  17. Losartan and captopril treatment rescue normal thrombus formation in microfibril associated glycoprotein-1 (MAGP1) deficient mice.

    PubMed

    Vassequi-Silva, Tallita; Pereira, Danielle Sousa; Nery Diez, Ana Cláudia C; Braga, Guilherme G; Godoy, Juliana A; Mendes, Camila B; Dos Santos, Leonardo; Krieger, José E; Antunes, Edson; Costa, Fábio T M; Vicente, Cristina P; Werneck, Claudio C

    2016-02-01

    MAGP1 is a glycoprotein present in the elastic fibers and is a part of the microfibrils components. MAGP1 interacts with von Willebrand factor and the active form of TGF-β and BMP. In mice lacking MAGP1, thrombus formation is delayed, increasing the occlusion time of carotid artery despite presenting normal blood coagulation in vitro. MAGP1-containing microfibrils may play a role in hemostasis and thrombosis. In this work, we evaluated the function of MAGP1 and its relation to TGF-β in the arterial thrombosis process. We analyzed thrombus formation time in wild type and MAGP1-deficient mice comparing Rose Bengal and Ferric Chloride induced arterial lesion. The potential participation of TGF-β in this process was accessed when we treated both wild type and MAGP1-deficient mice with losartan (an antihypertensive drug that decreases TGF-β activity) or captopril (an angiotensin converting enzyme inhibitor that was used as a control antihypertensive drug). Besides, we evaluated thrombus embolization and the gelatinolytic activity in the arterial walls in vitro and ex vivo. Losartan and captopril were able to recover the thrombus formation time without changing blood pressure, activated partial thromboplastin time (aPTT), PT (prothrombin time), platelet aggregation and adhesion, but decreased gelatinase activity. Our results suggest that both treatments are effective in the prevention of the sub-endothelial ECM degradation, allowing the recovery of normal thrombus formation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Endothelial progenitor cells bind and inhibit platelet function and thrombus formation.

    PubMed

    Abou-Saleh, Haissam; Yacoub, Daniel; Théorêt, Jean-François; Gillis, Marc-Antoine; Neagoe, Paul-Eduard; Labarthe, Benoit; Théroux, Pierre; Sirois, Martin G; Tabrizian, Maryam; Thorin, Eric; Merhi, Yahye

    2009-12-01

    Interactions of endothelial progenitor cells (EPCs) with vascular and blood cells contribute to vascular homeostasis. Although platelets promote the homing of EPCs to sites of vascular injury and their differentiation into endothelial cells, the functional consequences of such interactions on platelets remain unknown. Herein, we addressed the interactions between EPCs and platelets and their impact on platelet function and thrombus formation. Cultured on fibronectin in conditioned media, human peripheral blood mononuclear cells differentiated, within 10 days of culture, into EPCs, which uptake acetylated low-density lipoprotein, bind ulex-lectin, lack monocyte/leukocyte markers (CD14, P-selectin glycoprotein ligand-1, L-selectin), express progenitor/endothelial markers (CD34, vascular endothelial growth factor receptor-2, von Willebrand factor, and vascular endothelial cadherin), and proliferate in culture. These EPCs bound activated platelets via CD62P and inhibited its translocation, glycoprotein IIb/IIIa activation, aggregation, and adhesion to collagen, mainly via prostacyclin secretion. Indeed, this was associated with upregulation of cyclooxygenase-2 and inducible nitric oxide synthase. However, the effects on platelets in vitro were reversed by cyclooxygenase and cyclooxygenase-2 inhibition but not by nitric oxide or inducible nitric oxide synthase inhibition. Moreover, in a ferric chloride-induced murine arterial thrombosis model, injection of EPCs led to their incorporation into sites of injury and impaired thrombus formation, leading to an incomplete occlusion with 50% residual flow. Peripheral blood mononuclear cell-derived EPCs bind platelets via CD62P and inhibit platelet activation, aggregation, adhesion to collagen, and thrombus formation, predominantly via upregulation of cyclooxygenase-2 and secretion of prostacyclin. These findings add new insights into the biology of EPCs and define their potential roles in regulating platelet function and

  19. Endothelial Progenitor Cells Bind and Inhibit Platelet Function and Thrombus Formation

    PubMed Central

    Abou-Saleh, Haissam; Yacoub, Daniel; Théorêt, Jean-François; Gillis, Marc-Antoine; Neagoe, Paul-Eduard; Labarthe, Benoit; Théroux, Pierre; Sirois, Martin G.; Tabrizian, Maryam; Thorin, Eric; Merhi, Yahye

    2013-01-01

    Background Interactions of endothelial progenitor cells (EPCs) with vascular and blood cells contribute to vascular homeostasis. Although platelets promote the homing of EPCs to sites of vascular injury and their differentiation into endothelial cells, the functional consequences of such interactions on platelets remain unknown. Herein, we addressed the interactions between EPCs and platelets and their impact on platelet function and thrombus formation. Methods and Results Cultured on fibronectin in conditioned media, human peripheral blood mononuclear cells differentiated, within 10 days of culture, into EPCs, which uptake acetylated low-density lipoprotein, bind ulex-lectin, lack monocyte/leukocyte markers (CD14, P-selectin glycoprotein ligand-1, L-selectin), express progenitor/endothelial markers (CD34, vascular endothelial growth factor receptor-2, von Willebrand factor, and vascular endothelial cadherin), and proliferate in culture. These EPCs bound activated platelets via CD62P and inhibited its translocation, glycoprotein IIb/IIIa activation, aggregation, and adhesion to collagen, mainly via prostacyclin secretion. Indeed, this was associated with upregulation of cyclooxygenase-2 and inducible nitric oxide synthase. However, the effects on platelets in vitro were reversed by cyclooxygenase and cyclooxygenase-2 inhibition but not by nitric oxide or inducible nitric oxide synthase inhibition. Moreover, in a ferric chloride–induced murine arterial thrombosis model, injection of EPCs led to their incorporation into sites of injury and impaired thrombus formation, leading to an incomplete occlusion with 50% residual flow. Conclusions Peripheral blood mononuclear cell– derived EPCs bind platelets via CD62P and inhibit platelet activation, aggregation, adhesion to collagen, and thrombus formation, predominantly via upregulation of cyclooxygenase-2 and secretion of prostacyclin. These findings add new insights into the biology of EPCs and define their potential

  20. Vascular Nitric Oxide-Superoxide Balance and Thrombus Formation after Acute Exercise.

    PubMed

    Przyborowski, Kamil; Proniewski, Bartosz; Czarny, Joanna; Smeda, Marta; Sitek, Barbara; Zakrzewska, Agnieszka; Zoladz, Jerzy A; Chlopicki, Stefan

    2018-02-21

    An acute bout of strenuous exercise in humans results in transient impairment of NO-dependent function, but it remains unknown whether this phenomenon is associated with increased risk of post-exercise thrombotic events. This study aimed to evaluate effects of a single bout of exhaustive running in mice on the balance of vascular nitric oxide (NO)/reactive oxygen species (ROS) production, and on thrombogenicity. At different time-points (0h, 2h and 4h) after exercise and in sedentary C57BL/6 mice the production of NO and superoxide (O2) in aorta was measured by electron paramagnetic resonance (EPR) spin trapping and by dihydroethidium (DHE)/HPLC-based method, respectively, while collagen-induced thrombus formation was analyzed in a microchip-based flow-chamber system (T-TAS). We also measured pre- and post-exercise plasma concentration of nitrite/nitrate and 6-keto-PGF1α. An acute bout of exhaustive running in mice resulted in decreased production of NO and increased production of O2 in aorta, with maximum changes 2h after completion of exercise when compared to sedentary mice. However, platelet thrombus formation was not changed by exercise as evidenced by unaltered time to start of thrombus formation (T10) and capillary occlusion (OT), and total thrombogenicity (AUC) as measured in a flow-chamber system. Strenuous exercise increased the plasma concentration of nitrite but did not affect nitrate and 6-keto-PGF1α concentrations. An acute bout of strenuous exercise in mice reduced NO and in parallel increased O2 production in aorta. This response was most pronounced 2h after exercise. Surprisingly, the reduced NO and increased O2 production did not result in increased post-exercise platelet-dependent thrombogenicity. These results show that transient reduction in NO bioavailability, caused by exercise-induced oxidative stress, does not modify post-exercise thromboresistance in healthy mice.

  1. Cathepsin G-Dependent Modulation of Platelet Thrombus Formation In Vivo by Blood Neutrophils

    PubMed Central

    Faraday, Nauder; Schunke, Kathryn; Saleem, Sofiyan; Fu, Juan; Wang, Bing; Zhang, Jian; Morrell, Craig; Dore, Sylvain

    2013-01-01

    Neutrophils are consistently associated with arterial thrombotic morbidity in human clinical studies but the causal basis for this association is unclear. We tested the hypothesis that neutrophils modulate platelet activation and thrombus formation in vivo in a cathepsin G-dependent manner. Neutrophils enhanced aggregation of human platelets in vitro in dose-dependent fashion and this effect was diminished by pharmacologic inhibition of cathepsin G activity and knockdown of cathepsin G expression. Tail bleeding time in the mouse was prolonged by a cathepsin G inhibitor and in cathepsin G knockout mice, and formation of neutrophil-platelet conjugates in blood that was shed from transected tails was reduced in the absence of cathepsin G. Bleeding time was highly correlated with blood neutrophil count in wildtype but not cathepsin G deficient mice. In the presence of elevated blood neutrophil counts, the anti-thrombotic effect of cathepsin G inhibition was greater than that of aspirin and additive to it when administered in combination. Both pharmacologic inhibition of cathepsin G and its congenital absence prolonged the time for platelet thrombus to form in ferric chloride-injured mouse mesenteric arterioles. In a vaso-occlusive model of ischemic stroke, inhibition of cathepsin G and its congenital absence improved cerebral blood flow, reduced histologic brain injury, and improved neurobehavioral outcome. These experiments demonstrate that neutrophil cathepsin G is a physiologic modulator of platelet thrombus formation in vivo and has potential as a target for novel anti-thrombotic therapies. PMID:23940756

  2. Thrombus resolution and hemodynamic recovery using ultrasound-accelerated thrombolysis in acute pulmonary embolism.

    PubMed

    Kennedy, Robert J; Kenney, Hai H; Dunfee, Brian L

    2013-06-01

    To evaluate retrospectively the safety profile and clinical success of ultrasound-accelerated thrombolysis for acute pulmonary embolism (PE) with a standard lytic infusion protocol. A retrospective study was performed at a single center treating patients with acute PE between October 2009 and April 2012. On diagnosis of submassive or massive PE by pulmonary computed tomography angiography or ventilation/perfusion scan, all patients received anticoagulation and treatment using the EkoSonic endovascular system (EKOS Corporation, Bothell, Washington). The ultrasound-accelerated thrombolytic infusion catheters were placed into the affected pulmonary arteries to facilitate administration of recombinant tissue plasminogen activator at 0.5-1.0mg/h/catheter. Treatment of 60 patients (35 men, 25 women; age 61 y±16; 53 bilateral PE; 48 submassive PE) resulted in complete thrombus clearance (≥90%) in 57% and near-complete (50%-90%) clearance in 41% of patients after infusion of 35.1 mg±11.1 of recombinant tissue plasminogen activator over 19.6 hours±6.0. Measurements before and after treatment showed a decrease in pulmonary artery pressure (47 mm Hg±15 to 38 mm Hg±12 [systolic], P<.001) and Miller score (25±3 to 17±6, P<.001). There were 57 patients who survived to discharge. All three patients who died in the hospital presented with massive PE. On 90-day follow-up, 56 patients (93%) were alive. The current study demonstrates effectiveness and safety of ultrasound-accelerated thrombolysis in patients with acute PE with a large thrombus burden. Copyright © 2013 SIR. Published by Elsevier Inc. All rights reserved.

  3. Cancer cell–derived microparticles bearing P-selectin glycoprotein ligand 1 accelerate thrombus formation in vivo

    PubMed Central

    Thomas, Grace M.; Panicot-Dubois, Laurence; Lacroix, Romaric; Dignat-George, Françoise; Lombardo, Dominique

    2009-01-01

    Recent publications have demonstrated the presence of tissue factor (TF)–bearing microparticles (MPs) in the blood of patients suffering from cancer. However, whether these MPs are involved in thrombosis remains unknown. We show that pancreatic and lung cancer cells produce MPs that express active TF and P-selectin glycoprotein ligand 1 (PSGL-1). Cancer cell–derived MPs aggregate platelets via a TF-dependent pathway. In vivo, cancer cell–derived MPs, but not their parent cells, infused into a living mouse accumulate at the site of injury and reduce tail bleeding time and the time to occlusion of venules and arterioles. This thrombotic state is also observed in mice developing tumors. In such mice, the amount of circulating platelet-, endothelial cell–, and cancer cell–derived MPs is increased. Endogenous cancer cell–derived MPs shed from the growing tumor are able to accumulate at the site of injury. Infusion of a blocking P-selectin antibody abolishes the thrombotic state observed after injection of MPs or in mice developing a tumor. Collectively, our results indicate that cancer cell–derived MPs bearing PSGL-1 and TF play a key role in thrombus formation in vivo. Targeting these MPs could be of clinical interest in the prevention of thrombosis and to limit formation of metastasis in cancer patients. PMID:19667060

  4. Acute failure of a St. Jude's prosthetic aortic valve: large pannus formation masked by a small thrombus.

    PubMed

    Hurwitz, Seth Eric; Waxman, Daniel; Hecht, Susan

    2009-09-01

    Pannus formation and valve thrombus can cause prosthetic valve failure. The authors report the case of a 50-year-old woman who presented to the emergency room with decompensated heart failure secondary to mechanical valve dysfunction. On two-dimensional and transesophageal echocardiography, the patient had severe aortic stenosis and regurgitation. A thrombus seen on the valve was felt to be the etiology of her prosthetic valve failure. She underwent emergent cardiac surgery for aortic valve replacement. Pathology revealed that although a small thrombus was present, extensive pannus was the underlying mechanism of valve dysfunction. Differentiation between pannus and thrombus may have important clinical implications, but this case illustrates that distinguishing between these entities by echocardiographic and clinical criteria may not be possible.

  5. Functional Divergence of Platelet Protein Kinase C (PKC) Isoforms in Thrombus Formation on Collagen*

    PubMed Central

    Gilio, Karen; Harper, Matthew T.; Cosemans, Judith M. E. M.; Konopatskaya, Olga; Munnix, Imke C. A.; Prinzen, Lenneke; Leitges, Michael; Liu, Qinghang; Molkentin, Jeffery D.; Heemskerk, Johan W. M.; Poole, Alastair W.

    2010-01-01

    Arterial thrombosis, a major cause of myocardial infarction and stroke, is initiated by activation of blood platelets by subendothelial collagen. The protein kinase C (PKC) family centrally regulates platelet activation, and it is becoming clear that the individual PKC isoforms play distinct roles, some of which oppose each other. Here, for the first time, we address all four of the major platelet-expressed PKC isoforms, determining their comparative roles in regulating platelet adhesion to collagen and their subsequent activation under physiological flow conditions. Using mouse gene knock-out and pharmacological approaches in human platelets, we show that collagen-dependent α-granule secretion and thrombus formation are mediated by the conventional PKC isoforms, PKCα and PKCβ, whereas the novel isoform, PKCθ, negatively regulates these events. PKCδ also negatively regulates thrombus formation but not α-granule secretion. In addition, we demonstrate for the first time that individual PKC isoforms differentially regulate platelet calcium signaling and exposure of phosphatidylserine under flow. Although platelet deficient in PKCα or PKCβ showed reduced calcium signaling and phosphatidylserine exposure, these responses were enhanced in the absence of PKCθ. In summary therefore, this direct comparison between individual subtypes of PKC, by standardized methodology under flow conditions, reveals that the four major PKCs expressed in platelets play distinct non-redundant roles, where conventional PKCs promote and novel PKCs inhibit thrombus formation on collagen. PMID:20479008

  6. Functional divergence of platelet protein kinase C (PKC) isoforms in thrombus formation on collagen.

    PubMed

    Gilio, Karen; Harper, Matthew T; Cosemans, Judith M E M; Konopatskaya, Olga; Munnix, Imke C A; Prinzen, Lenneke; Leitges, Michael; Liu, Qinghang; Molkentin, Jeffery D; Heemskerk, Johan W M; Poole, Alastair W

    2010-07-23

    Arterial thrombosis, a major cause of myocardial infarction and stroke, is initiated by activation of blood platelets by subendothelial collagen. The protein kinase C (PKC) family centrally regulates platelet activation, and it is becoming clear that the individual PKC isoforms play distinct roles, some of which oppose each other. Here, for the first time, we address all four of the major platelet-expressed PKC isoforms, determining their comparative roles in regulating platelet adhesion to collagen and their subsequent activation under physiological flow conditions. Using mouse gene knock-out and pharmacological approaches in human platelets, we show that collagen-dependent alpha-granule secretion and thrombus formation are mediated by the conventional PKC isoforms, PKCalpha and PKCbeta, whereas the novel isoform, PKC, negatively regulates these events. PKCdelta also negatively regulates thrombus formation but not alpha-granule secretion. In addition, we demonstrate for the first time that individual PKC isoforms differentially regulate platelet calcium signaling and exposure of phosphatidylserine under flow. Although platelet deficient in PKCalpha or PKCbeta showed reduced calcium signaling and phosphatidylserine exposure, these responses were enhanced in the absence of PKC. In summary therefore, this direct comparison between individual subtypes of PKC, by standardized methodology under flow conditions, reveals that the four major PKCs expressed in platelets play distinct non-redundant roles, where conventional PKCs promote and novel PKCs inhibit thrombus formation on collagen.

  7. Redirection of arachidonic acid metabolism by ICI D1542: effects on thrombus formation in the coronary artery of the anaesthetized dog.

    PubMed Central

    McAuliffe, S. J.; Moors, J. A.; Snow, H. M.; Wayne, M.; Jessup, R.

    1993-01-01

    1. The effects of simultaneous redirection of arachidonic acid metabolism, by inhibition of thromboxane A2 (TXA2) synthase and blockade of the platelet thromboxane A2 receptor (TP-receptor), was examined on the rate of thrombus formation in a stenosed coronary artery with damaged endothelium in an anaesthetized dog. 2. Redirection of arachidonic acid metabolism was achieved by intravenous doses of ICI D1542, a selective and potent inhibitor of TXA2 synthase and the TP-receptor. 3. Redirection of arachidonic acid metabolism was demonstrated in whole blood, stimulated ex vivo by collagen. The ED50 for inhibition of TXB2 production was 7.1 micrograms kg-1, i.v.; there were corresponding increases in the production of the eicosanoids prostaglandin D2 (PGD2), PGE2 and PGF2 alpha. 4. Thrombus formation was inhibited by D1542 (ED50 0.55 micrograms kg-1, i.v.), but could be restarted by an intravenous infusion of adrenaline (0.2-38 micrograms kg-1 min-1, i.v.). In the presence of the maximum effective dose of D1542 (1 mg kg-1, i.v.) a 190 fold increase in the infusion rate of adrenaline was required to restore thrombus formation. 5. In the presence of D1542, removal of endoperoxide metabolites by inhibition of cyclo-oxygenase with aspirin (5 mg kg-1, i.v.) caused thrombus formation to restart, indicating the ability of the endoperoxide metabolites to inhibit thrombus formation in vivo. 6. These results indicate that, in the stenosed and damaged coronary artery of the dog, redirection of arachidonic acid metabolism by D1542 is more effective at preventing thrombus formation than inhibition of cyclo-oxygenase by aspirin. PMID:8485629

  8. Development of real-time and quantitative monitoring of thrombus formation in an extracorporeal centrifugal blood pump

    NASA Astrophysics Data System (ADS)

    Sakota, Daisuke; Fujiwara, Tatsuki; Ohuchi, Katsuhiro; Kuwana, Katsuyuki; Yamazaki, Hiroyuki; Kosaka, Ryo; Maruyama, Osamu

    2018-02-01

    We developed an optical detector of thrombus formed on the pivot bearing of an extracorporeal centrifugal blood pump (MERA HCF-MP23; Senko Medical Instrument Mfg. Co., Ltd., Tokyo, Japan) which is frequently used for long-term extracorporeal circulation support to bridge to an implantable artificial heart, which in turn is used for bridge to heart transplantation in Japan. In this study, we investigated the quantitative performance of the thrombus formation in acute animal experiments. A total of three experiments of extracorporeal left ventricular assist using Japanese specific pathogen-free pigs were conducted. The optical fibers were set in the pump driver unit. The incident light at nearinfrared wavelength aiming at the pivot bearing and the resulting scattered light were guided to respective fibers. The detected signal was analyzed to obtain thrombus formation level (TFL) calculated by a specially developed software. When the increase in TFL was confirmed, the pump was exchanged and the extracorporeal circulation was restarted. The number of pump exchanges were four times at each experiment so a total of twelve pumps were evaluated. 3-dimentional data surrounding the pivot bearing and the adhered thrombus was captured by a 3-dimantional surface measurement system to calculate the thrombus surface area (TSA) formed on the pivot bearing. As a result, the correlation coefficient between TFL and TSA was 0.878. The accuracy of TSA estimated by the optical detector was 3.6+/-2.3 mm2. This was small enough to not have the pump exchanged in clinical judgement. The developed detector would be useful for optimal anti-coagulation management.

  9. Multi-Constituent Simulation of Thrombus Deposition

    NASA Astrophysics Data System (ADS)

    Wu, Wei-Tao; Jamiolkowski, Megan A.; Wagner, William R.; Aubry, Nadine; Massoudi, Mehrdad; Antaki, James F.

    2017-02-01

    In this paper, we present a spatio-temporal mathematical model for simulating the formation and growth of a thrombus. Blood is treated as a multi-constituent mixture comprised of a linear fluid phase and a thrombus (solid) phase. The transport and reactions of 10 chemical and biological species are incorporated using a system of coupled convection-reaction-diffusion (CRD) equations to represent three processes in thrombus formation: initiation, propagation and stabilization. Computational fluid dynamic (CFD) simulations using the libraries of OpenFOAM were performed for two illustrative benchmark problems: in vivo thrombus growth in an injured blood vessel and in vitro thrombus deposition in micro-channels (1.5 mm × 1.6 mm × 0.1 mm) with small crevices (125 μm × 75 μm and 125 μm × 137 μm). For both problems, the simulated thrombus deposition agreed very well with experimental observations, both spatially and temporally. Based on the success with these two benchmark problems, which have very different flow conditions and biological environments, we believe that the current model will provide useful insight into the genesis of thrombosis in blood-wetted devices, and provide a tool for the design of less thrombogenic devices.

  10. Multi-Constituent Simulation of Thrombus Deposition

    PubMed Central

    Wu, Wei-Tao; Jamiolkowski, Megan A.; Wagner, William R.; Aubry, Nadine; Massoudi, Mehrdad; Antaki, James F.

    2017-01-01

    In this paper, we present a spatio-temporal mathematical model for simulating the formation and growth of a thrombus. Blood is treated as a multi-constituent mixture comprised of a linear fluid phase and a thrombus (solid) phase. The transport and reactions of 10 chemical and biological species are incorporated using a system of coupled convection-reaction-diffusion (CRD) equations to represent three processes in thrombus formation: initiation, propagation and stabilization. Computational fluid dynamic (CFD) simulations using the libraries of OpenFOAM were performed for two illustrative benchmark problems: in vivo thrombus growth in an injured blood vessel and in vitro thrombus deposition in micro-channels (1.5 mm × 1.6 mm × 0.1 mm) with small crevices (125 μm × 75 μm and 125 μm × 137 μm). For both problems, the simulated thrombus deposition agreed very well with experimental observations, both spatially and temporally. Based on the success with these two benchmark problems, which have very different flow conditions and biological environments, we believe that the current model will provide useful insight into the genesis of thrombosis in blood-wetted devices, and provide a tool for the design of less thrombogenic devices. PMID:28218279

  11. Multi-Constituent Simulation of Thrombus Deposition.

    PubMed

    Wu, Wei-Tao; Jamiolkowski, Megan A; Wagner, William R; Aubry, Nadine; Massoudi, Mehrdad; Antaki, James F

    2017-02-20

    In this paper, we present a spatio-temporal mathematical model for simulating the formation and growth of a thrombus. Blood is treated as a multi-constituent mixture comprised of a linear fluid phase and a thrombus (solid) phase. The transport and reactions of 10 chemical and biological species are incorporated using a system of coupled convection-reaction-diffusion (CRD) equations to represent three processes in thrombus formation: initiation, propagation and stabilization. Computational fluid dynamic (CFD) simulations using the libraries of OpenFOAM were performed for two illustrative benchmark problems: in vivo thrombus growth in an injured blood vessel and in vitro thrombus deposition in micro-channels (1.5 mm × 1.6 mm × 0.1 mm) with small crevices (125 μm × 75 μm and 125 μm × 137 μm). For both problems, the simulated thrombus deposition agreed very well with experimental observations, both spatially and temporally. Based on the success with these two benchmark problems, which have very different flow conditions and biological environments, we believe that the current model will provide useful insight into the genesis of thrombosis in blood-wetted devices, and provide a tool for the design of less thrombogenic devices.

  12. Evaluation of the antithrombotic abilities of non-vitamin K antagonist oral anticoagulants using the Total Thrombus-formation Analysis System®.

    PubMed

    Idemoto, Yoshiaki; Miura, Shin-Ichiro; Norimatsu, Kenji; Suematsu, Yasunori; Hitaka, Yuka; Shiga, Yuhei; Morii, Joji; Imaizumi, Satoshi; Kuwano, Takashi; Iwata, Atsushi; Zhang, Bo; Ogawa, Masahiro; Saku, Keijiro

    2017-03-01

    The Total Thrombus-formation Analysis System (T-TAS ® ) is a novel automated microchip flow-chamber system for the quantitative evaluation of thrombus formation under blood flow conditions. T-TAS ® uses two types of microchip to evaluate thrombus formation: the AR-chip quantifies white thrombus formation and the PL-chip quantifies platelet thrombus formation. We assessed the antithrombotic abilities of various non-vitamin K antagonist oral anticoagulants (NOACs) using T-TAS ® . One hundred and three consecutive patients who were hospitalized with cardiovascular diseases were enrolled. We divided the patients into 2 groups; a control group that did not receive an anticoagulant (non-AC group) and an anticoagulant group (AC group). The AC group was further divided into warfarin, dabigatran, rivaroxaban and apixaban groups. We performed common coagulation tests and evaluated the area under the flow pressure curve (AR-AUC and PL-AUC) to quantify antithrombotic ability using T-TAS ® at the trough. There were no significant differences in patient characteristics between the non-AC and AC groups. Only 55.1 % of patients in the AC group achieved the target blood pressure (BP) of less than 130/80 mmHg. Compared with the non-AC group, AR-AUC was significantly decreased in the AC, warfarin, dabigatran and apixaban groups. Only the rivaroxaban group did not show a significant decrease in AR-AUC. NOACs showed a significant decrease in PL-AUC compared with the non-AC group. In conclusion, T-TAS ® was a useful tool for evaluating anticoagulation activity. NOACs was significantly effective as an antiplatelet agent. BP control should be a higher priority than the selection of an anticoagulant drug, especially NOACs.

  13. Genetic Analysis of the Role of Protein Kinase Cθ in Platelet Function and Thrombus Formation

    PubMed Central

    Hall, Kellie J.; Harper, Matthew T.; Gilio, Karen; Cosemans, Judith M.; Heemskerk, Johan W. M.; Poole, Alastair W.

    2008-01-01

    Background PKCθ is a novel protein kinase C isozyme, predominately expressed in T cells and platelets. PKCθ−/− T cells exhibit reduced activation and PKCθ−/− mice are resistant to autoimmune disease, making PKCθ an attractive therapeutic target for immune modulation. Collagen is a major agonist for platelets, operating through an immunoreceptor-like signalling pathway from its receptor GPVI. Although it has recently been shown that PKCθ positively regulates outside-in signalling through integrin αIIbβ3 in platelets, the role of PKCθ in GPVI-dependent signalling and functional activation of platelets has not been assessed. Methodology/Principal Findings In the present study we assessed static adhesion, cell spreading, granule secretion, integrin αIIbβ3 activation and platelet aggregation in washed mouse platelets lacking PKCθ. Thrombus formation on a collagen-coated surface was assessed in vitro under flow. PKCθ−/− platelets exhibited reduced static adhesion and filopodia generation on fibrinogen, suggesting that PKCθ positively regulates outside-in signalling, in agreement with a previous report. In contrast, PKCθ−/− platelets also exhibited markedly enhanced GPVI-dependent α-granule secretion, although dense granule secretion was unaffected, suggesting that PKCθ differentially regulates these two granules. Inside-out regulation of αIIbβ3 activation was also enhanced downstream of GPVI stimulation. Although this did not result in increased aggregation, importantly thrombus formation on collagen under high shear (1000 s−1) was enhanced. Conclusions/Significance These data suggest that PKCθ is an important negative regulator of thrombus formation on collagen, potentially mediated by α-granule secretion and αIIbβ3 activation. PKCθ therefore may act to restrict thrombus growth, a finding that has important implications for the development and safe clinical use of PKCθ inhibitors. PMID:18815612

  14. Effect of wood smoke exposure on vascular function and thrombus formation in healthy fire fighters.

    PubMed

    Hunter, Amanda L; Unosson, Jon; Bosson, Jenny A; Langrish, Jeremy P; Pourazar, Jamshid; Raftis, Jennifer B; Miller, Mark R; Lucking, Andrew J; Boman, Christoffer; Nyström, Robin; Donaldson, Kenneth; Flapan, Andrew D; Shah, Anoop S V; Pung, Louis; Sadiktsis, Ioannis; Masala, Silvia; Westerholm, Roger; Sandström, Thomas; Blomberg, Anders; Newby, David E; Mills, Nicholas L

    2014-12-09

    Myocardial infarction is the leading cause of death in fire fighters and has been linked with exposure to air pollution and fire suppression duties. We therefore investigated the effects of wood smoke exposure on vascular vasomotor and fibrinolytic function, and thrombus formation in healthy fire fighters. In a double-blind randomized cross-over study, 16 healthy male fire fighters were exposed to wood smoke (~1 mg/m³ particulate matter concentration) or filtered air for one hour during intermittent exercise. Arterial pressure and stiffness were measured before and immediately after exposure, and forearm blood flow was measured during intra-brachial infusion of endothelium-dependent and -independent vasodilators 4-6 hours after exposure. Thrombus formation was assessed using the ex vivo Badimon chamber at 2 hours, and platelet activation was measured using flow cytometry for up to 24 hours after the exposure. Compared to filtered air, exposure to wood smoke increased blood carboxyhaemoglobin concentrations (1.3% versus 0.8%; P < 0.001), but had no effect on arterial pressure, augmentation index or pulse wave velocity (P > 0.05 for all). Whilst there was a dose-dependent increase in forearm blood flow with each vasodilator (P < 0.01 for all), there were no differences in blood flow responses to acetylcholine, sodium nitroprusside or verapamil between exposures (P > 0.05 for all). Following exposure to wood smoke, vasodilatation to bradykinin increased (P = 0.003), but there was no effect on bradykinin-induced tissue-plasminogen activator release, thrombus area or markers of platelet activation (P > 0.05 for all). Wood smoke exposure does not impair vascular vasomotor or fibrinolytic function, or increase thrombus formation in fire fighters. Acute cardiovascular events following fire suppression may be precipitated by exposure to other air pollutants or through other mechanisms, such as strenuous physical exertion and dehydration.

  15. Thrombus formation in the interrupted segment of the aorta.

    PubMed

    Karavelioğlu, Yusuf; Kalçık, Macit; Yetim, Mucahit; Doğan, Tolga; Gölbaşı, Zehra

    2017-06-01

    Interrupted aorta is a very rare heart defect in which there is a gap between the ascending and the descending thoracic aorta. It is usually associated with other cardiac anomalies, including ventricular septal defect, ductus arteriosus, and truncus arteriosus. Severe cases present with serious complications such as hypertension, heart failure, or intracranial hemorrhage. Neurological complications are very rare form of presentation and commonly associated with intracranial aneurysms. We have reported a case of interrupted aorta who presented with transient ischemic attack due to thrombus formation in the interrupted segment of the aorta. © 2017, Wiley Periodicals, Inc.

  16. Complementary roles of platelets and coagulation in thrombus formation on plaques acutely ruptured by targeted ultrasound treatment: a novel intravital model.

    PubMed

    Kuijpers, M J E; Gilio, K; Reitsma, S; Nergiz-Unal, R; Prinzen, L; Heeneman, S; Lutgens, E; van Zandvoort, M A M J; Nieswandt, B; Egbrink, M G A Oude; Heemskerk, J W M

    2009-01-01

    Atherothrombosis is a major cause of cardiovascular events. However, animal models to study this process are scarce. We describe the first murine model of acute thrombus formation upon plaque rupture to study atherothrombosis by intravital fluorescence microscopy. Localized rupture of an atherosclerotic plaque in a carotid artery from Apoe(-/-) mice was induced in vivo using ultrasound. Rupture of the plaque and formation of localized thrombi were verified by two-photon laser scanning microscopy (TPLSM) in isolated arteries, and by immunohistochemistry. The thrombotic reaction was quantified by intravital fluorescence microscopy. Inspection of the ultrasound-treated plaques by histochemistry and TPLSM demonstrated local damage, collagen exposure, luminal thrombus formation as well as intra-plaque intrusion of erythrocytes and fibrin. Ultrasound treatment of healthy carotid arteries resulted in endothelial damage and limited platelet adhesion. Real-time intravital fluorescence microscopy demonstrated rapid platelet deposition on plaques and formation of a single thrombus that remained subocclusive. The thrombotic process was antagonized by thrombin inhibition, or by blocking of collagen or adenosine diphosphate receptor pathways. Multiple thrombi were formed in 70% of mice lacking CD40L. Targeted rupture of murine plaques results in collagen exposure and non-occlusive thrombus formation. The thrombotic process relies on platelet activation as well as on thrombin generation and coagulation, and is sensitive to established and novel antithrombotic medication. This model provides new possibilities to study atherothrombosis in vivo.

  17. Dangerous liaison: successful percutaneous edge-to-edge mitral valve repair in patients with end-stage systolic heart failure can cause left ventricular thrombus formation.

    PubMed

    Orban, Martin; Braun, Daniel; Sonne, Carolin; Orban, Mathias; Thaler, Raffael; Grebmer, Christian; Lesevic, Hasema; Schömig, Albert; Mehilli, Julinda; Massberg, Steffen; Hausleiter, Jörg

    2014-06-01

    To evaluate the characteristics and clinical outcome of patients with new formation of left ventricular (LV) thrombus after percutaneous edge-to-edge mitral valve repair. Between 2009 and 2012 we intended to treat 150 patients with severe mitral regurgitation (MR) with percutaneous edge-to-edge mitral valve repair in our centre. Post-procedural transthoracic echocardiographic examinations scheduled during the hospital stay revealed the new formation of LV thrombi in three out of 150 patients. All three patients suffered from end-stage systolic heart failure with a LV ejection fraction (LVEF) below 20% and were successfully treated in terms of MR reduction (reduction of at least two MR grades). No thrombus formation was observed in patients with a LVEF >20% treated in our centre (a total of 136 patients). The frequency of new LV thrombus formation in the cohort of patients with a LVEF ≤20% treated in our centre was 21% (three out of 14 patients). New formation of LV thrombus was detected in patients with severely depressed LVEF (≤20%) after successful reduction of MR following percutaneous edge-to-edge mitral valve repair. This phenomenon could be a play of chance, but percutaneous edge-to-edge mitral valve repair using the MitraClip¨ system is a new procedure. Special care is needed when performing new procedures, and the unexpected post-procedural finding of LV thrombus formation in approximately 20% in this cohort is worth reporting.

  18. P-selectin ligation induces platelet activation and enhances microaggregate and thrombus formation.

    PubMed

    Théorêt, Jean-François; Yacoub, Daniel; Hachem, Ahmed; Gillis, Marc-Antoine; Merhi, Yahye

    2011-09-01

    Platelet P-selectin is a thrombo-inflammatory molecule involved in platelet activation and aggregation. This may occur via the adhesive function of P-selectin and its potential capacity to trigger intracellular signaling. However, its impact on platelet function remains elusive. This study was therefore designed to investigate the relationship between the signaling potential of platelet P-selectin and its function in platelet physiology. Human and mouse platelets were freshly isolated from whole blood. Platelet activation was assessed using flow cytometry and western blot analysis, while platelet physiological responses were evaluated through aggregation, microaggregate formation and in a thrombosis model in wild-type and P-selectin-deficient (CD62P(-/-)) mice. Interaction of P-selectin with its high-affinity ligand, a recombinant soluble form of P-Selectin Glycoprotein Ligand-1 (rPSGL-1), enhances platelet activation, adhesion and microaggregate formation. This augmented platelet microaggregates requires an intact cytoskeleton, but occurs independently of platelet α(IIb)β(3). Thrombus formation and microaggregate were both enhanced by rPSGL-1 in wild-type, but not in CD62P(-/-) mice. In addition, CD62P(-/-) mice exhibited thrombosis abnormalities without an α(IIb)β(3) activation defect. This study demonstrates that the role of platelet P-selectin is not solely adhesive; its binding to PSGL-1 induces platelet activation that enhances platelet aggregation and thrombus formation. Therefore, targeting platelet P-selectin or its ligand PSGL-1 could provide a potential therapeutic approach in the management of thrombotic disorders. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Critical role of FcR gamma-chain, LAT, PLCgamma2 and thrombin in arteriolar thrombus formation upon mild, laser-induced endothelial injury in vivo.

    PubMed

    Kalia, Neena; Auger, Jocelyn M; Atkinson, Ben; Watson, Steve P

    2008-05-01

    The role of collagen receptor complex GPVI-FcR gamma-chain, PLCgamma2 and LAT in laser-induced thrombosis is unclear. Controversy surrounds whether collagen is exposed in this model or whether thrombosis is dependent on thrombin. This study hypothesized that collagen exposure plays a critical role in thrombus formation in this model, which was tested by investigating contributions of FcR gamma-chain, LAT, PLCgamma2 and thrombin. Thrombi were monitored using intravital microscopy in anesthetized wild-type and FcR gamma-chain, LAT and PLCgamma2 knockout mice. Hirudin (thrombin inhibitor) was administered to wild-type and FcR gamma-chain knockout mice. Significantly reduced thrombus formation was observed in FcR gamma-chain and PLCgamma2 knockouts with a greater decrease observed in LAT knockouts. Dramatic reduction was observed in wild-types treated with hirudin, with abolished thrombus formation only observed in FcR gamma-chain knockouts treated with hirudin. GPVI-FcR gamma-chain, LAT and PLCgamma2 are essential for thrombus generation and stability in this laser-induced model of injury. More importantly, a greater role for LAT was identified, which may reflect a role for it downstream of a second matrix protein receptor. However, inhibition of platelet activation by matrix proteins and thrombin generation are both required to maximally prevent thrombus formation.

  20. Sensitivity analysis of geometrical parameters to study haemodynamics and thrombus formation in the left atrial appendage.

    PubMed

    García-Isla, Guadalupe; Olivares, Andy Luis; Silva, Etelvino; Nuñez-Garcia, Marta; Butakoff, Constantine; Sanchez-Quintana, Damian; G Morales, Hernán; Freixa, Xavier; Noailly, Jérôme; De Potter, Tom; Camara, Oscar

    2018-05-08

    The left atrial appendage (LAA) is a complex and heterogeneous protruding structure of the left atrium (LA). In atrial fibrillation patients, it is the location where 90% of the thrombi are formed. However, the role of the LAA in thrombus formation is not fully known yet. The main goal of this work is to perform a sensitivity analysis to identify the most relevant LA and LAA morphological parameters in atrial blood flow dynamics. Simulations were run on synthetic ellipsoidal left atria models where different parameters were individually studied: pulmonary veins and mitral valve dimensions; LAA shape; and LA volume. Our computational analysis confirmed the relation between large LAA ostia, low blood flow velocities and thrombus formation. Additionally, we found that pulmonary vein configuration exerted a critical influence on LAA blood flow patterns. These findings contribute to a better understanding of the LAA and to support clinical decisions for atrial fibrillation patients. Copyright © 2018 John Wiley & Sons, Ltd.

  1. Image-based characterization of thrombus formation in time-lapse DIC microscopy

    PubMed Central

    Brieu, Nicolas; Navab, Nassir; Serbanovic-Canic, Jovana; Ouwehand, Willem H.; Stemple, Derek L.; Cvejic, Ana; Groher, Martin

    2012-01-01

    The characterization of thrombus formation in time-lapse DIC microscopy is of increased interest for identifying genes which account for atherothrombosis and coronary artery diseases (CADs). In particular, we are interested in large-scale studies on zebrafish, which result in large amount of data, and require automatic processing. In this work, we present an image-based solution for the automatized extraction of parameters quantifying the temporal development of thrombotic plugs. Our system is based on the joint segmentation of thrombotic and aortic regions over time. This task is made difficult by the low contrast and the high dynamic conditions observed in vivo DIC microscopic scenes. Our key idea is to perform this segmentation by distinguishing the different motion patterns in image time series rather than by solving standard image segmentation tasks in each image frame. Thus, we are able to compensate for the poor imaging conditions. We model motion patterns by energies based on the idea of dynamic textures, and regularize the model by two prior energies on the shape of the aortic region and on the topological relationship between the thrombus and the aorta. We demonstrate the performance of our segmentation algorithm by qualitative and quantitative experiments on synthetic examples as well as on real in vivo microscopic sequences. PMID:22482997

  2. Interleukin-6 mediates enhanced thrombus development in cerebral arterioles following a brief period of focal brain ischemia

    PubMed Central

    Tang, Ya Hui; Vital, Shantel; Russell, Janice; Seifert, Hilary; Granger, D. Neil

    2015-01-01

    Objective The cerebral microvasculature is rendered more vulnerable to thrombus formation following a brief (5.0 min) period of focal ischemia. This study examined the contribution of interleukin-6 (IL-6), a neuroprotective and prothrombotic cytokine produced by the brain, to transient ischemia-induced thrombosis in cerebral arterioles. Approach & results The middle cerebral artery of C57BL/6J mice was occluded for 5 minutes, followed by 24 hrs of reperfusion (MCAo/R). Intravital fluorescence microscopy was used to monitor thrombus development in cerebral arterioles induced by light/dye photoactivation. Thrombosis was quantified as the time of onset of platelet aggregation on the vessel wall and the time for complete blood flow cessation. MCAo/R in wild type (WT) mice yielded an acceleration of thrombus formation that was accompanied by increased IL-6 levels in plasma and in post-ischemic brain tissue. The exaggerated thrombosis response to MCAo/R was blunted in WT mice receiving an IL-6 receptor-blocking antibody and in IL-6 deficient (IL-6−/−) mice. Bone marrow chimeras, produced by transplanting IL-6−/− marrow into WT recipients, did not exhibit protection against MCAo/R-induced thrombosis. Conclusions The increased vulnerability of the cerebral vasculature to thrombus development after MCAo/R is mediated by IL-6, which is likely derived from brain cells rather than circulating blood cells. These findings suggest that anti-IL-6 therapy may reduce the likelihood of cerebral thrombus development after a transient ischemic attack. PMID:26054883

  3. Non-redundant roles of phosphoinositide 3-kinase isoforms alpha and beta in glycoprotein VI-induced platelet signaling and thrombus formation.

    PubMed

    Gilio, Karen; Munnix, Imke C A; Mangin, Pierre; Cosemans, Judith M E M; Feijge, Marion A H; van der Meijden, Paola E J; Olieslagers, Servé; Chrzanowska-Wodnicka, Magdalena B; Lillian, Rivka; Schoenwaelder, Simone; Koyasu, Shigeo; Sage, Stewart O; Jackson, Shaun P; Heemskerk, Johan W M

    2009-12-04

    Platelets are activated by adhesion to vascular collagen via the immunoglobulin receptor, glycoprotein VI (GPVI). This causes potent signaling toward activation of phospholipase Cgamma2, which bears similarity to the signaling pathway evoked by T- and B-cell receptors. Phosphoinositide 3-kinase (PI3K) plays an important role in collagen-induced platelet activation, because this activity modulates the autocrine effects of secreted ADP. Here, we identified the PI3K isoforms directly downstream of GPVI in human and mouse platelets and determined their role in GPVI-dependent thrombus formation. The targeting of platelet PI3Kalpha or -beta strongly and selectively suppressed GPVI-induced Ca(2+) mobilization and inositol 1,4,5-triphosphate production, thus demonstrating enhancement of phospholipase Cgamma2 by PI3Kalpha/beta. That PI3Kalpha and -beta have a non-redundant function in GPVI-induced platelet activation and thrombus formation was concluded from measurements of: (i) serine phosphorylation of Akt, (ii) dense granule secretion, (iii) intracellular Ca(2+) increases and surface expression of phosphatidylserine under flow, and (iv) thrombus formation, under conditions where PI3Kalpha/beta was blocked or p85alpha was deficient. In contrast, GPVI-induced platelet activation was insensitive to inhibition or deficiency of PI3Kdelta or -gamma. Furthermore, PI3Kalpha/beta, but not PI3Kgamma, contributed to GPVI-induced Rap1b activation and, surprisingly, also to Rap1b-independent platelet activation via GPVI. Together, these findings demonstrate that both PI3Kalpha and -beta isoforms are required for full GPVI-dependent platelet Ca(2+) signaling and thrombus formation, partly independently of Rap1b. This provides a new mechanistic explanation for the anti-thrombotic effect of PI3K inhibition and makes PI3Kalpha an interesting new target for anti-platelet therapy.

  4. Total Thrombus-formation Analysis System Predicts Periprocedural Bleeding Events in Patients With Coronary Artery Disease Undergoing Percutaneous Coronary Intervention.

    PubMed

    Oimatsu, Yu; Kaikita, Koichi; Ishii, Masanobu; Mitsuse, Tatsuro; Ito, Miwa; Arima, Yuichiro; Sueta, Daisuke; Takahashi, Aya; Iwashita, Satomi; Yamamoto, Eiichiro; Kojima, Sunao; Hokimoto, Seiji; Tsujita, Kenichi

    2017-04-24

    Periprocedural bleeding events are common after percutaneous coronary intervention. We evaluated the association of periprocedural bleeding events with thrombogenicity, which was measured quantitatively by the Total Thrombus-formation Analysis System equipped with microchips and thrombogenic surfaces (collagen, platelet chip [PL]; collagen plus tissue factor, atheroma chip [AR]). Between August 2013 and March 2016, 313 consecutive patients with coronary artery disease undergoing elective percutaneous coronary intervention were enrolled. They were divided into those with or without periprocedural bleeding events. We determined the bleeding events as composites of major bleeding events defined by the International Society on Thrombosis and Hemostasis and minor bleeding events (eg, minor hematoma, arteriovenous shunt and pseudoaneurysm). Blood samples obtained at percutaneous coronary intervention were analyzed for thrombus formation area under the curve (PL 24 -AUC 10 for PL chip; AR 10 -AUC 30 for AR chip) by the Total Thrombus-formation Analysis System and P2Y12 reaction unit by the VerifyNow system. Periprocedural bleeding events occurred in 37 patients. PL 24 -AUC 10 levels were significantly lower in patients with such events than those without ( P =0.002). Multiple logistic regression analyses showed association between low PL 24 -AUC 10 levels and periprocedural bleeding events (odds ratio, 2.71 [1.22-5.99]; P =0.01) and association between PL 24 -AUC 10 and periprocedural bleeding events in 176 patients of the femoral approach group (odds ratio, 2.88 [1.11-7.49]; P =0.03). However, PL 24 -AUC 10 levels in 127 patients of the radial approach group were not significantly different in patients with or without periprocedural bleeding events. PL 24 -AUC 10 measured by the Total Thrombus-formation Analysis System is a potentially useful predictor of periprocedural bleeding events in coronary artery disease patients undergoing elective percutaneous coronary

  5. Effects of Cone-Shaped Bend Inlet Cannulas of an Axial Blood Pump on Thrombus Formation: An Experiment and Simulation Study.

    PubMed

    Liu, Guangmao; Zhou, Jianye; Sun, Hansong; Zhang, Yan; Chen, Haibo; Hu, Shengshou

    2017-04-05

    BACKGROUND Cannula shape and connection style influence the risk of thrombus formation in the blood pump by varying the blood flow characteristics inside the pump. Inlet cannulas should be designed based on the need for anatomical fit and reducing the risk of thrombus generation in the blood pump. The effects on thrombus formation of the cone-shaped bend inlet cannulas of axial blood pumps should be studied. MATERIAL AND METHODS The cannulas were designed as cone-shaped, with 1 bent section connecting 2 straight sections. Both the silicone tube and novel cone-shaped cannula were simulated for comparison. The flow fields of a blood pump with inlet cannula were simulated by computational fluid dynamics (CFD) at flows of 2.0, 2.5, and 3.0 liters per minute (lpm), with pump rotational speeds of 7500, 8000, and 8500 rpm, respectively. Then, 6 two-dimensional (2D) particle image velocimetry (PIV) tests were conducted and the velocity distributions were analyzed. RESULTS A low-velocity region was located inside the pump entrance when a soft silicone tube was used. At 8500 rpm and 3.0 lpm working condition, the minimum velocity inside the pump with cone-shaped cannulas was 2.5×10^-1 m/s. The cone-shaped cannulas eliminated the low-velocity region inside the pump. Both CFD and PIV results showed that the low-velocity region did not spread to the entrance of the blood pump within the flow range from 2.0 lpm to 7.0 lpm. CONCLUSIONS The designed cone-shaped bent cannulas can eliminate the low-velocity region inside the blood pump and reduce the risk of thrombus formation in the blood pump.

  6. Modulation of Platelet Activation and Thrombus Formation Using a Pan-PI3K Inhibitor S14161

    PubMed Central

    Ren, Lijie; Liu, Xiaohui; Wang, Qi; He, Sudan; Wu, Qingyu; Hu, Hu; Mao, Xinliang; Zhu, Li

    2014-01-01

    The phosphatidylinositol 3–kinase (PI3K) signaling pathway is critical in modulating platelet functions. In the present study, we evaluated the effect of S14161, a recently identified pan-class I PI3K inhibitor, on platelet activation and thrombus formation. Results showed that S14161 inhibited human platelet aggregation induced by collagen, thrombin, U46619, and ADP in a dose-dependent manner. Flow cytometric studies showed that S14161 inhibited convulxin- or thrombin-induced P-selectin expression and fibrinogen binding of single platelet. S14161 also inhibited platelet spreading on fibrinogen and clot retraction, processes mediated by outside-in signaling. Using a microfluidic chamber we demonstrated that S14161 decreased platelet adhesion on collagen-coated surface by about 80%. Western blot showed that S14161 inhibited phosphorylation of Akt at both Ser473 and Thr308 sites, and GSK3β at Ser9 in response to collagen, thrombin, or U46619. Comparable studies showed that S14161 has a higher potential bioavailability than LY294002, a prototypical inhibitor of pan-class I PI3K. Finally, the effects of S14161 on thrombus formation in vivo were measured using a ferric chloride-induced carotid artery injury model in mice. The intraperitoneal injection of S14161 (2 mg/kg) to male C57BL/6 mice significantly extended the first occlusion time (5.05±0.99 min, n = 9) compared to the vehicle controls (3.72±0.95 min, n = 8) (P<0.05), but did not prolong the bleeding time (P>0.05). Taken together, our data showed that S14161 inhibits platelet activation and thrombus formation without significant bleeding tendency and toxicity, and considering its potential higher bioavailability, it may be developed as a novel therapeutic agent for the prevention of thrombotic disorders. PMID:25115838

  7. Distinct contributions of complement factors to platelet activation and fibrin formation in venous thrombus development

    PubMed Central

    Jäckel, Sven; Saffarzadeh, Mona; Langer, Florian

    2017-01-01

    Expanding evidence indicates multiple interactions between the hemostatic system and innate immunity, and the coagulation and complement cascades. Here we show in a tissue factor (TF)–dependent model of flow restriction-induced venous thrombosis that complement factors make distinct contributions to platelet activation and fibrin deposition. Complement factor 3 (C3) deficiency causes prolonged bleeding, reduced thrombus incidence, thrombus size, fibrin and platelet deposition in the ligated inferior vena cava, and diminished platelet activation in vitro. Initial fibrin deposition at the vessel wall over 6 hours in this model was dependent on protein disulfide isomerase (PDI) and TF expression by myeloid cells, but did not require neutrophil extracellular trap formation involving peptidyl arginine deiminase 4. In contrast to C3−/− mice, C5-deficient mice had no apparent defect in platelet activation in vitro, and vessel wall platelet deposition and initial hemostasis in vivo. However, fibrin formation, the exposure of negatively charged phosphatidylserine (PS) on adherent leukocytes, and clot burden after 48 hours were significantly reduced in C5−/− mice compared with wild-type controls. These results delineate that C3 plays specific roles in platelet activation independent of formation of the terminal complement complex and provide in vivo evidence for contributions of complement-dependent membrane perturbations to prothrombotic TF activation on myeloid cells. PMID:28223279

  8. White thrombus formation in blood tubing lines in a chronic hemodialysis unit.

    PubMed

    Watnick, Suzanne; Stooksbury, Michael; Winter, Rolf; Riscoe, Michael; Cohen, David M

    2008-03-01

    Previous reports have described white particulate matter in banked blood components, but no prior public reports describe such matter in blood tubing during the course of routine in-center hemodialysis. This report describes the events, investigations, and preliminary conclusions associated with the spontaneous formation of adherent white thrombus in the venous and arterial blood lines during routine in-center hemodialysis treatments. Design setting, participants, & measurements: This investigation occurred at the Portland Veterans Administration Medical Center (PVAMC) Hemodialysis Unit from October 2006 through April 2007. Sixty-eight variables regarding demographics, medical history and dialysis treatments were collected on our 34 chronic hemodialysis outpatients. Over a 5-wk interval, 62% (21 of 34) of the chronic hemodialysis patients unexpectedly developed a white precipitate adhering to the lumenal surface of their dialysis blood tubing, with 73 of 580 chronic dialysis treatments exhibiting the phenomenon. Microscopic and biochemical analyses were consistent with white thrombus, formed by an aggregation of platelets and fibrin. An alert was issued and other in-center hemodialysis units noted similar findings. This was remedied by the removal of specific tubing. Both patient-specific and tubing-specific factors may have been operative. Although patient safety was not adversely affected, assessment of clinical and manufacturing variables potentially affecting platelet activation is warranted.

  9. Protein kinase C mediates platelet secretion and thrombus formation through protein kinase D2.

    PubMed

    Konopatskaya, Olga; Matthews, Sharon A; Harper, Matthew T; Gilio, Karen; Cosemans, Judith M E M; Williams, Christopher M; Navarro, Maria N; Carter, Deborah A; Heemskerk, Johan W M; Leitges, Michael; Cantrell, Doreen; Poole, Alastair W

    2011-07-14

    Platelets are highly specialized blood cells critically involved in hemostasis and thrombosis. Members of the protein kinase C (PKC) family have established roles in regulating platelet function and thrombosis, but the molecular mechanisms are not clearly understood. In particular, the conventional PKC isoform, PKCα, is a major regulator of platelet granule secretion, but the molecular pathway from PKCα to secretion is not defined. Protein kinase D (PKD) is a family of 3 kinases activated by PKC, which may represent a step in the PKC signaling pathway to secretion. In the present study, we show that PKD2 is the sole PKD member regulated downstream of PKC in platelets, and that the conventional, but not novel, PKC isoforms provide the upstream signal. Platelets from a gene knock-in mouse in which 2 key phosphorylation sites in PKD2 have been mutated (Ser707Ala/Ser711Ala) show a significant reduction in agonist-induced dense granule secretion, but not in α-granule secretion. This deficiency in dense granule release was responsible for a reduced platelet aggregation and a marked reduction in thrombus formation. Our results show that in the molecular pathway to secretion, PKD2 is a key component of the PKC-mediated pathway to platelet activation and thrombus formation through its selective regulation of dense granule secretion.

  10. Increased Levels of Markers of Oxidative Stress and Inflammation in Patients with Rheumatic Mitral Stenosis Predispose to Left Atrial Thrombus Formation

    PubMed Central

    Pulimamidi, Vinay Kumar; Murugesan, Vengatesan; Rajappa, Medha; Satheesh, Santhosh; Harichandrakumar, Kottenyen Thazhath

    2013-01-01

    Background: Rheumatic mitral stenosis (MS) causes stagnation of blood flow, leading to thrombus formation in the left atrium (LA), which may lead to systemic thromboembolic complications. We compared alterations in circulating levels of pro-/anti–oxidants and markers of inflammation in patients of severe rheumatic MS with and without LA thrombus and studied their predictive power to detect the presence of LA thrombus in patients with rheumatic MS. Material and Methods: This is a cross-sectional study of 80 patients with rheumatic MS, evaluated for percutaneous mitral commisurotomy. Group 1 comprised of patients with rheumatic MS with LA thrombus (n=35) and Group 2 included patients with rheumatic MS without LA thrombus (n=45). The following oxidative stress markers-malondialdehyde (MDA), protein carbonyls, total oxidant status and total antioxidant status and inflammation markers-high sensitivity C-reactive protein (hs-CRP), total sialic acid (TSA) and protein-bound sialic acid (PBSA) were estimated in all study subjects. Results: Levels of plasma MDA, protein carbonyl and total oxidant status were significantly elevated, whilst the total antioxidant status levels were significantly lowered, in Group 1, as compared with Group 2. hs-CRP, TSA and PBSA levels showed a significant rise in Group 1 patients, as compared with Group 2. Conclusion: Our results suggest that circulating levels of MDA, protein carbonyl and PBSA were independent predictors of occurrence of LA thrombus in patients with rheumatic MS. PMID:24392368

  11. Dabigatran Etexilate Reduces Thrombin-Induced Inflammation and Thrombus Formation in Experimental Ischemic Stroke.

    PubMed

    Dittmeier, Melanie; Wassmuth, Kathrin; Schuhmann, Michael K; Kraft, Peter; Kleinschnitz, Christoph; Fluri, Felix

    2016-01-01

    Dabigatran etexilate (DE), a direct-acting, oral inhibitor of thrombin, significantly reduces the risk of stroke compared with traditional anticoagulants, without increasing the risk of major bleeding. However, studies on the fate of cerebral tissue after ischemic stroke in patients receiving DE are sparse and the role of dabigatran-mediated reduction of thrombin in this context has not yet been investigated. Here, we investigated whether pretreatment with DE reduces thrombin-mediated pro-inflammatory mechanisms and leakage of the blood-brain barrier (BBB) following ischemic stroke in rats. Male Wistar rats received DE (15 mg/kg) or a vehicle solution 1 hour before transient middle cerebral artery occlusion (tMCAO) for 90 minutes. Infarct volume, neurologic outcome and intracranial hemorrhage (ICH) were determined after tMCAO. Thrombin generation was indirectly assessed by measuring thrombin/antithrombin III complex. Microvascular patency was evaluated histologically. Cytokine expression and immunoreactivity of cluster of differentiation (CD) 68 were examined to characterize inflammatory processes after pretreatment with DE. BBB integrity was examined by quantifying brain edema. Rats given DE revealed a significant reduction in infarct size without an increase in ICH and significant recovery of neurologic deficits compared to controls. Administration of DE decreased thrombin generation and thrombus formation, dampened the CD68-immunoreactivity and attenuated pro-inflammatory cytokine expression in the cerebral parenchyma ipsilateral to the ischemic lesion. BBB permeability was unaltered following treatment with DE. In summary, prophylactic anticoagulation with DE improves stroke outcome by reducing thrombin-induced inflammation and thrombus formation without increasing the rate of ICH.

  12. White Thrombus Formation in Blood Tubing Lines in a Chronic Hemodialysis Unit

    PubMed Central

    Watnick, Suzanne; Stooksbury, Michael; Winter, Rolf; Riscoe, Michael; Cohen, David M.

    2008-01-01

    Background and objectives: Previous reports have described white particulate matter in banked blood components, but no prior public reports describe such matter in blood tubing during the course of routine in-center hemodialysis. This report describes the events, investigations, and preliminary conclusions associated with the spontaneous formation of adherent white thrombus in the venous and arterial blood lines during routine in-center hemodialysis treatments. Design setting, participants, & measurements: This investigation occurred at the Portland Veterans Administration Medical Center (PVAMC) Hemodialysis Unit from October 2006 through April 2007. Sixty-eight variables regarding demographics, medical history and dialysis treatments were collected on our 34 chronic hemodialysis outpatients. Results: Over a 5-wk interval, 62% (21 of 34) of the chronic hemodialysis patients unexpectedly developed a white precipitate adhering to the lumenal surface of their dialysis blood tubing, with 73 of 580 chronic dialysis treatments exhibiting the phenomenon. Microscopic and biochemical analyses were consistent with white thrombus, formed by an aggregation of platelets and fibrin. An alert was issued and other in-center hemodialysis units noted similar findings. This was remedied by the removal of specific tubing. Conclusions: Both patient-specific and tubing-specific factors may have been operative. Although patient safety was not adversely affected, assessment of clinical and manufacturing variables potentially affecting platelet activation is warranted. PMID:18184880

  13. Thrombus aspiration in acute myocardial infarction: concepts, clinical trials, and current guidelines.

    PubMed

    Vandermolen, Sebastian; Marciniak, Maciej; Byrne, Jonathan; De Silva, Kalpa

    2016-05-01

    The pathogenesis that underlies acute myocardial infarction is complex and multifactorial. One of the most important components, however, is the role of thrombus formation following atherosclerotic plaque rupture, leading to sudden coronary occlusion and subsequent ischemia and infarction. Thrombus aspiration provides the opportunity of intracoronary clot extraction with the aim to improve coronary and myocardial perfusion, by reducing the risk of no-reflow secondary to distal embolization of thrombus. The utility of thrombus aspiration during primary percutaneous coronary intervention has been assessed in an increasing number of observational and randomized studies. This article reviews the contemporary data and provides insights into the validity of thrombus aspiration in the setting of acute myocardial infarction.

  14. Cooperative integrin/ITAM signaling in platelets enhances thrombus formation in vitro and in vivo

    PubMed Central

    Zhi, Huiying; Rauova, Lubica; Hayes, Vincent; Gao, Cunji; Boylan, Brian; Newman, Debra K.; McKenzie, Steven E.; Cooley, Brian C.; Poncz, Mortimer; Newman, Peter J.

    2013-01-01

    The integrin family is composed of a series of 24 αβ heterodimer transmembrane adhesion receptors that mediate cell-cell and cell-extracellular matrix interactions. Adaptor molecules bearing immunoreceptor tyrosine-based activation motifs (ITAMs) have recently been shown to cooperate with specific integrins to increase the efficiency of transmitting ligand-binding–induced signals into cells. In human platelets, Fc receptor γ-chain IIa (FcγRIIa) has been identified as an ITAM-bearing transmembrane receptor responsible for mediating “outside-in” signaling through αIIbβ3, the major adhesion receptor on the platelet surface. To explore the importance of FcγRIIa in thrombosis and hemostasis, we subjected FcγRIIa-negative and FcγRIIa-positive murine platelets to a number of well-accepted models of platelet function. Compared with their FcγRIIa-negative counterparts, FcγRIIa-positive platelets exhibited increased tyrosine phosphorylation of Syk and phospholipase Cγ2 and increased spreading upon interaction with immobilized fibrinogen, retracted a fibrin clot faster, and showed markedly enhanced thrombus formation when perfused over a collagen-coated flow chamber under conditions of arterial and venous shear. They also displayed increased thrombus formation and fibrin deposition in in vivo models of vascular injury. Taken together, these data establish FcγRIIa as a physiologically important functional conduit for αIIbβ3-mediated outside-in signaling, and suggest that modulating the activity of this novel integrin/ITAM pair might be effective in controlling thrombosis. PMID:23264598

  15. Protective mechanisms of adenosine 5'-monophosphate in platelet activation and thrombus formation.

    PubMed

    Fuentes, E; Badimon, L; Caballero, J; Padró, T; Vilahur, G; Alarcón, M; Pérez, P; Palomo, I

    2014-03-03

    Platelet activation is relevant to a variety of acute thrombotic events. We sought to examine adenosine 5'-monophosphate (AMP) mechanisms of action in preventing platelet activation, thrombus formation and platelet-related inflammatory response. We assessed the effect of AMP on 1) P-selectin expression and GPIIb/IIIa activation by flow cytometry; 2) Platelet aggregation and ATP secretion induced by ADP, collagen, TRAP-6, convulxin and thrombin; 3) Platelet rolling and firm adhesion, and platelet-leukocyte interactions under flow-controlled conditions; and, 4) Platelet cAMP levels, sP-selectin, sCD40L, IL-1β, TGF-β1 and CCL5 release, PDE3A activity and PKA phosphorylation. The effect of AMP on in vivo thrombus formation was also evaluated in a murine model. The AMP docking with respect to A2 adenosine receptor was determined by homology. AMP concentration-dependently (0.1 to 3 mmol/l) inhibited P-selectin expression and GPIIb/IIIa activation, platelet secretion and aggregation induced by ADP, collagen, TRAP-6 and convulxin, and diminished platelet rolling and firm adhesion. Furthermore, AMP induced a marked increase in the rolling speed of leukocytes retained on the platelet surface. At these concentrations AMP significantly decreased inflammatory mediator from platelet, increased intraplatelet cAMP levels and inhibited PDE3A activity. Interestingly, SQ22536, ZM241385 and SCH58261 attenuated the antiplatelet effect of AMP. Docking experiments revealed that AMP had the same orientation that adenosine inside the A2 adenosine receptor binding pocket. These in vitro antithrombotic properties were further supported in an in vivo model of thrombosis. Considering the successful use of combined antiplatelet therapy, AMP may be further developed as a novel antiplatelet agent.

  16. Minimally invasive vein therapy and treatment options for endovenous heat-induced thrombus.

    PubMed

    Frasier, Krista; Latessa, Victoria

    2008-06-01

    Radiofrequency ablation and endovenous laser therapy are types of minimally invasive techniques that have been used in the treatment of chronic venous insufficiency. In both procedures, high-intensity heat via thermal energy is produced and delivered via an endovenous catheter placed in the saphenous vein. This results in changes that therapeutically induce closure of the vein by denaturing the vessel wall with subsequent thrombus formation. Patients undergo ultrasound 48 to 72 hours postprocedure to confirm vessel occlusion and assess for possible extension of thrombus into the deep venous system. Thrombus is frequently visualized with the procedure in the tributaries, the venous dilations, and at times the saphenofemoral junction. In any other setting, thrombus at the saphenofemoral junction would warrant anticoagulation. However, the characteristics, composition, and behavior of endovenous heat-induced thrombus are different than de novo thrombosis. This postprocedure endovenous heat-induced thrombus is considered a normal consequence of the procedure and does not require traditional anticoagulation in most cases, depending on the location.

  17. Glaucocalyxin A Inhibits Platelet Activation and Thrombus Formation Preferentially via GPVI Signaling Pathway

    PubMed Central

    Li, Qiang; Ren, Lijie; Liu, Xiaohui; Chu, Chunjun; Ozaki, Yukio; Zhang, Jian; Zhu, Li

    2013-01-01

    Platelets play a pivotal role in atherothrombosis and the antiplatelet agents have been proved to be useful in preventing onset of acute clinical events including myocardial infarction and stroke. Increasing number of natural compounds has been identified to be potential antiplatelet agents. Here we report the antiplatelet effect of glaucocalyxin A (GLA), an ent-diterpenoid that we isolated and purified from the aerial parts of Rabdosia japonica (Burm. f.) var. glaucocalyx (Maxim.) Hara, and investigate the molecular mechanisms by which GLA inhibits platelet activation and thrombus formation. The effect of GLA on platelet activation was measured using platelets freshly isolated from peripheral blood of healthy donors. Results showed that pretreatment of human platelets with lower concentrations of GLA (0.01μg/ml, 0.1μg/ml) significantly inhibited platelet aggregation induced by collagen (P<0.001) and CRP (P<0.01), a synthetic GPVI ligand, but not by ADP and U46619. Accordingly, GLA inhibited collagen-stimulated tyrosine phosphorylation of Syk, LAT, and phospholipase Cγ2, the signaling events in collagen receptor GPⅥ pathway. GLA also inhibited platelet p-selectin secretion and integrin activation by convulxin, a GPVI selective ligand. Additionally, GLA was found to inhibit low-dose thrombin-induced platelet activation. Using a flow chamber device, GLA was found to attenuate platelet adhesion on collagen surfaces in high shear condition. In vivo studies showed that GLA administration increased the time for complete occlusion upon vascular injury in mice, but did not extend tail-bleeding time when mice were administered with relatively lower doses of GLA. Therefore, the present results provide the molecular basis for the inhibition effect of GLA on platelet activation and its in vivo effect on thrombus formation, suggesting that GLA could potentially be developed as an antiplatelet and antithrombotic agent. PMID:24386454

  18. Method of cell transplantation promoting the organization of intraarterial thrombus.

    PubMed

    Hirano, Koji; Shimono, Takatsugu; Imanaka-Yoshida, Kyoko; Miyamoto, Keiichi; Fujinaga, Kazuya; Kajimoto, Masaki; Miyake, Yoichiro; Nishikawa, Masakatsu; Yoshida, Toshimichi; Uchida, Atsumasa; Shimpo, Hideto; Yada, Isao; Hirata, Hitoshi

    2005-08-30

    Endovascular aortic repairs have been developed as less invasive treatments for aortic aneurysms. Some aneurismal cavities, however, remain without organization, causing a re-expansion of the aneurysms. We studied cell transplantation into the aneurismal sac to promote the organization of thrombus for the complete healing of aneurysms. Skin fibroblasts and skeletal myoblasts were isolated from rats for cell transplantation. An intraarterial thrombus model was made by ligation of the carotid artery. Culture medium (medium group, n=11), collagen gel (gel group, n=11), fibroblasts with collagen gel (F group, n=15), myoblasts with collagen gel (M group, n=12), or mixture of fibroblasts and myoblasts with collagen gel (F+M group, n=14) were injected into the thrombus. After 28 days, histologically, the arterial lumens of the F and M groups were partly filled with fibrous tissues, whereas in the F+M group organization was almost completed and luminal sizes diminished. Immunohistochemical staining demonstrated that alpha-smooth muscle actin-positive cells were more abundantly contained in the organized area of the F+M group than in the other groups. We also analyzed cellular function in vitro with immunofluorescence; coculture of fibroblasts and myoblasts showed that the fraction of alpha-smooth muscle actin-positive fibroblasts increased. This phenomenon accounts for the rapid organization of thrombus in the F+M group in vivo. Cell transplantation accelerated thrombus organization. Especially, myoblasts enhanced differentiation of fibroblasts into myofibroblasts, contributing to rapid thrombus organization. Cell transplantation into unorganized spaces seems applicable to endovascular treatment of aneurysms.

  19. High-density lipoprotein from patients with coronary heart disease loses anti-thrombotic effects on endothelial cells: impact on arterial thrombus formation.

    PubMed

    Holy, Erik W; Besler, Christian; Reiner, Martin F; Camici, Giovanni G; Manz, Jasmin; Beer, Jürg H; Lüscher, Thomas F; Landmesser, Ulf; Tanner, Felix C

    2014-11-01

    Thrombus formation is determined by the balance between pro- thrombotic mediators and anti-thrombotic factors.High-density lipoprotein (HDL) from healthy subjects exerts anti-thrombotic properties. Whether this is also the case for HDL from patients with stable coronary heart disease (CHD) or acute coronary syndrome (ACS) is unknown.In human aortic endothelial cells in culture,HDL (50 µg/ml) from healthy subjects (HS) inhibited thrombin-induced tissue factor (TF) expression and activity, while HDL (50 µg/ml) from CHD and ACS patients did not. Similarly, only healthy HDL increased endothelial tissue factor pathway inhibitor (TFPI) expression and tissue plasminogen activator (tPA) release, while HDL from CHD and ACS patients had no effect. Healthy HDL inhibited thrombin-induced plasminogen activator inhibitor type 1 (PAI-1) expression, while HDL from ACS patients enhanced endothelial PAI-1 expression. Inhibition of nitric oxide (NO) formation with L-NAME (100 µmol/l) abolished the anti-thrombotic effects of healthy HDL on TF, TFPI, and tPA expression. The exogenous nitric oxide donor, DETANO, mimicked the effects of healthy HDL and counterbalanced the loss of anti-thrombotic effects of HDL from CHD and ACS patients in endothelial cells. In line with this observation, healthy HDL, in contrast to HDL from CHD and ACS patients, increased endothelial NO production. In the laser-injured carotid artery of the mouse, thrombus formation was delayed in animals treated with healthy HDL compared with mice treated with vehicle or HDL from patients with CHD or ACS. In conclusion, HDL from CHD and ACS patients loses the ability of healthy HDL to suppress TF and to increase TFPI and t-PA and instead enhances PAI-1 and arterial thrombus formation.

  20. Endothelial LOX-1 activation differentially regulates arterial thrombus formation depending on oxLDL levels: role of the Oct-1/SIRT1 and ERK1/2 pathways.

    PubMed

    Akhmedov, Alexander; Camici, Giovanni G; Reiner, Martin F; Bonetti, Nicole R; Costantino, Sarah; Holy, Erik W; Spescha, Remo D; Stivala, Simona; Schaub Clerigué, Ariane; Speer, Thimoteus; Breitenstein, Alexander; Manz, Jasmin; Lohmann, Christine; Paneni, Francesco; Beer, Juerg-Hans; Lüscher, Thomas F

    2017-04-01

    The lectin-like oxLDL receptor-1 (LOX-1) promotes endothelial uptake of oxidized low-density lipoprotein (oxLDL) and plays an important role in atherosclerosis and acute coronary syndromes (ACS). However, its role in arterial thrombus formation remains unknown. We investigated whether LOX-1 plays a role in arterial thrombus formation in vivo at different levels of oxLDL using endothelial-specific LOX-1 transgenic mice (LOX-1TG) and a photochemical injury thrombosis model of the carotid artery. In mice fed a normal chow diet, time to arterial occlusion was unexpectedly prolonged in LOX-1TG as compared to WT. In line with this, tissue factor (TF) expression and activity in carotid arteries of LOX-1TG mice were reduced by half. This effect was mediated by activation of octamer transcription factor 1 (Oct-1) leading to upregulation of the mammalian deacetylase silent information regulator-two 1 (SIRT1) via binding to its promoter and subsequent inhibition of NF-κB signaling. In contrast, intravenous injection of oxLDL as well as high cholesterol diet for 6 weeks led to a switch from the Oct-1/SIRT1 signal transduction pathway to the ERK1/2 pathway and in turn to an enhanced thrombotic response with shortened occlusion time. Thus, LOX-1 differentially regulates thrombus formation in vivo depending on the degree of activation by oxLDL. At low oxLDL levels LOX-1 activates the protective Oct-1/SIRT1 pathway, while at higher levels of the lipoprotein switches to the thrombogenic ERK1/2 pathway. These findings may be important for arterial thrombus formation in ACS and suggest that SIRT1 may represent a novel therapeutic target in this context. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

  1. Platelet endothelial cell adhesion molecule 1 deficiency misguides venous thrombus resolution.

    PubMed

    Kellermair, Joerg; Redwan, Bassam; Alias, Sherin; Jabkowski, Joerg; Panzenboeck, Adelheid; Kellermair, Lukas; Winter, Max P; Weltermann, Ansgar; Lang, Irene M

    2013-11-07

    Platelet endothelial cell adhesion molecule 1 (PECAM-1) is involved in leukocyte migration and angiogenesis, which are key components of venous thrombus resolution. This study investigated the effect of PECAM-1 deficiency on thrombus resolution in FVB/n mice and the extent to which levels of soluble PECAM-1 (sPECAM-1) correlate with delayed thrombus resolution in humans after acute symptomatic deep vein thrombosis (DVT). In a mouse stagnant flow venous thrombosis model Pecam-1(-/-) thrombi were larger, persisted for longer periods of time, and displayed attenuated macrophage invasion and decreased vessel formation in the presence of increased fibrosis. In humans, higher levels of truncated plasma sPECAM-1 possibly cleaved from cell surfaces, were found in patients with delayed thrombus resolution (assessed via duplex-based thrombus scoring) relative to those whose thrombi resolved (median, 25th/75th percentile): 92.5 (87.7/103.4) ng/mL vs 71.5 (51.1/81.0) ng/mL; P < .001. Furthermore, unresolved human deep vein thrombus specimens stained positively with antibodies specific for the extracellular, but not the cytoplasmic domain of PECAM-1, consistent with accumulation of cleaved PECAM-1. Our data suggest a regulatory role of PECAM-1 in venous thrombus resolution and suggest a predictive value of sPECAM-1 for postthrombotic syndrome (PTS) after acute DVT.

  2. Incidence, Characteristics, and Clinical Course of Device-Related Thrombus After Watchman Left Atrial Appendage Occlusion Device Implantation in Atrial Fibrillation Patients.

    PubMed

    Kubo, Shunsuke; Mizutani, Yukiko; Meemook, Krissada; Nakajima, Yoshifumi; Hussaini, Asma; Kar, Saibal

    2017-12-11

    This study investigated characteristics and clinical impact of device-related thrombus formation after Watchman device implantation in atrial fibrillation (AF) patients. Left atrial appendage occlusion using the Watchman device is an effective alternative to anticoagulation for stroke prevention in AF patients. However, device-related thrombus formation remains an important concern after Watchman implantation. From 2006 to 2014, 119 consecutive AF patients underwent Watchman implantation. Transesophageal echocardiographic (TEE) follow-up was scheduled at 45 days, at 6 months, and at 12 months after the procedure. The incidence, characteristics, and clinical course of device-related thrombus formation detected by TEE were assessed. Follow-up TEE identified thrombus formation on the Watchman device in 4 patients (3.4%). The prevalence of chronic AF was 100% in patients with thrombus, which was higher than that for patients without thrombus (40.0%). Deployed device size was numerically larger in patients with thrombus (29.3 ± 3.8 mm vs. 25.7 ± 3.2 mm, respectively). All patients with thrombus discontinued any of the anticoagulant/antiplatelet therapy which was required under the study protocol. After restarting or continuing warfarin and aspirin therapy, complete resolution of the thrombus was achieved in all patients at subsequent follow-up TEE. Warfarin therapy was discontinued within 6 months for all cases, and there was no thrombus recurrence. The mean follow-up duration was 1,456 ± 546 days, with no death, stroke, or systemic embolization events in patients with thrombus. AF burden, device size, and anticoagulant/antiplatelet regimens can be associated with device-related thrombus after Watchman device implantation. Short-term warfarin therapy was effective, and the clinical outcomes were favorable. Copyright © 2017 American College of Cardiology Foundation. All rights reserved.

  3. Chlorogenic Acid Inhibits Human Platelet Activation and Thrombus Formation

    PubMed Central

    Fuentes, Eduardo; Caballero, Julio; Alarcón, Marcelo; Rojas, Armando; Palomo, Iván

    2014-01-01

    Background Chlorogenic acid is a potent phenolic antioxidant. However, its effect on platelet aggregation, a critical factor in arterial thrombosis, remains unclear. Consequently, chlorogenic acid-action mechanisms in preventing platelet activation and thrombus formation were examined. Methods and Results Chlorogenic acid in a dose-dependent manner (0.1 to 1 mmol/L) inhibited platelet secretion and aggregation induced by ADP, collagen, arachidonic acid and TRAP-6, and diminished platelet firm adhesion/aggregation and platelet-leukocyte interactions under flow conditions. At these concentrations chlorogenic acid significantly decreased platelet inflammatory mediators (sP-selectin, sCD40L, CCL5 and IL-1β) and increased intraplatelet cAMP levels/PKA activation. Interestingly, SQ22536 (an adenylate cyclase inhibitor) and ZM241385 (a potent A2A receptor antagonist) attenuated the antiplatelet effect of chlorogenic acid. Chlorogenic acid is compatible to the active site of the adenosine A2A receptor as revealed through molecular modeling. In addition, chlorogenic acid had a significantly lower effect on mouse bleeding time when compared to the same dose of aspirin. Conclusions Antiplatelet and antithrombotic effects of chlorogenic acid are associated with the A2A receptor/adenylate cyclase/cAMP/PKA signaling pathway. PMID:24598787

  4. Clot in Lung, Clot in Heart: A Case Report of Tumor-Like Thrombus in Right Atrium.

    PubMed

    Habibi, Roshanak; Altamirano, Alvaro J; Dadkhah, Shahriar

    2017-01-01

    Tumor-like formation of thrombus in the right atrial cavity is rare. It may be mistaken for a myxoma. The exact pathophysiology of an isolated thrombus in the heart is still unclear. Management to prevent complications such as pulmonary thromboembolism depends on the clinical judgment of a cardiologist. This report describes a 76-year-old woman with right atrial thrombus causing subsequent pulmonary thromboembolism in right lung. She initially presented to us with pulmonary embolism, and later, an incidental finding of a mass in her right atrium revealed an association of thrombus in heart with thrombus in lung. The challenging management was to resect this thrombus which was fixed to atrial septum, and a trial of anticoagulation did not resolve it. Exact management of such incidental findings in right heart cavities is not well established. Some cases may benefit from resection of such formed fixed thrombus.

  5. Clot in Lung, Clot in Heart: A Case Report of Tumor-Like Thrombus in Right Atrium

    PubMed Central

    Habibi, Roshanak; Altamirano, Alvaro J; Dadkhah, Shahriar

    2017-01-01

    Tumor-like formation of thrombus in the right atrial cavity is rare. It may be mistaken for a myxoma. The exact pathophysiology of an isolated thrombus in the heart is still unclear. Management to prevent complications such as pulmonary thromboembolism depends on the clinical judgment of a cardiologist. This report describes a 76-year-old woman with right atrial thrombus causing subsequent pulmonary thromboembolism in right lung. She initially presented to us with pulmonary embolism, and later, an incidental finding of a mass in her right atrium revealed an association of thrombus in heart with thrombus in lung. The challenging management was to resect this thrombus which was fixed to atrial septum, and a trial of anticoagulation did not resolve it. Exact management of such incidental findings in right heart cavities is not well established. Some cases may benefit from resection of such formed fixed thrombus. PMID:28579859

  6. Massive pulmonary embolism caused by internal iliac vein thrombosis with free-floating thrombus formation in the inferior vena cava.

    PubMed

    Brodmann, Marianne; Gary, Thomas; Hafner, Franz; Tiesenhausen, Kurt; Deutschmann, Hannes; Pilger, Enrst

    2012-04-01

    Nowadays, compression ultrasonography (CUS) is the gold standard for the routine diagnosis of deep venous thrombosis (DVT). The drawback of CUS is the low sensitivity concerning the diagnosis of isolated pelvic vein thrombosis, especially referring to isolated internal iliac vein and ovarian vein thromboses. Therefore, magnetic resonance (MR) venography has become a valuable alternative. We present the case of a 45-year-old female patient with a massive pulmonary embolism with the indication for thrombolytic therapy due to severe right ventricular overload. We were not able to detect a DVT in the lower limbs of this patient with CUS. However, further DVT workup by MR venography showed a free-floating thrombus formation originating from the right internal iliac veins into the inferior vena cava. Owing to the fact that this thrombus was free floating, surgical removal of the thrombus was scheduled and performed successfully. In some patients it might be important to look for so-called rare causes of pulmonary embolism, even when CUS of the lower limbs does not reveal any DVTs. The diagnostic procedure of choice for these patients seems to be MR phlebography, as iliac and pelvic veins can be evaluated without radiation exposure with this procedure. Copyright © 2012 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.

  7. Trivalent methylated arsenical-induced phosphatidylserine exposure and apoptosis in platelets may lead to increased thrombus formation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bae, Ok-Nam; Lim, Kyung-Min; AMOREPACIFIC CO/R and D Center, Gyeonggi-do 446-729

    2009-09-01

    Trivalent methylated metabolites of arsenic, monomethylarsonous acid (MMA{sup III}) and dimethylarsinous acid (DMA{sup III}), have been found highly reactive and toxic in various cells and in vivo animal models, suggesting their roles in the arsenic-associated toxicity. However, their effects on cardiovascular system including blood cells, one of the most important targets for arsenic toxicity, remain poorly understood. Here we found that MMA{sup III} and DMA{sup III} could induce procoagulant activity and apoptosis in platelets, which play key roles in the development of various cardiovascular diseases (CVDs) through excessive thrombus formation. In freshly isolated human platelets, treatment of MMA{sup III} resultedmore » in phosphatidylserine (PS) exposure, a hallmark of procoagulant activation, accompanied by distinctive apoptotic features including mitochondrial membrane potential disruption, cytochrome c release, and caspase-3 activation. These procoagulant activation and apoptotic features were found to be mediated by the depletion of protein thiol and intracellular ATP, and flippase inhibition by MMA{sup III}, while the intracellular calcium increase or reactive oxygen species generation was not involved. Importantly, increased platelet procoagulant activity by MMA{sup III} resulted in enhanced blood coagulation and excessive thrombus formation in a rat in vivo venous thrombosis model. DMA{sup III} also induced PS-exposure with apoptotic features mediated by protein thiol depletion, which resulted in enhanced thrombin generation. In summary, we believe that this study provides an important evidence for the role of trivalent methylated arsenic metabolites in arsenic-associated CVDs, giving a novel insight into the role of platelet apoptosis in toxicant-induced cardiovascular toxicity.« less

  8. The Adverse Survival Implications of Bland Thrombus in Renal Cell Carcinoma With Venous Tumor Thrombus.

    PubMed

    Hutchinson, Ryan; Rew, Charles; Chen, Gong; Woldu, Solomon; Krabbe, Laura-Maria; Meissner, Matthew; Sheth, Kunj; Singla, Nirmish; Shakir, Nabeel; Master, Viraj A; Karam, Jose A; Matin, Surena F; Borregales, Leonardo D; Wood, Christopher; Masterson, Timothy; Thompson, R Houston; Boorjian, Stephen A; Leibovich, Bradley C; Abel, E Jason; Bagrodia, Aditya; Margulis, Vitaly

    2018-05-01

    To characterize the presence of bland (nontumor) thrombus in advanced renal cell carcinoma and assess the impact of this finding on cancer-specific survival. A multi-institutional database of patients treated with nephrectomy with caval thrombectomy for locally-advanced renal tumors was assembled from 5 tertiary care medical centers. Using clinicopathologic variables including patient age, body mass index, Eastern Cooperative Oncology Group performance status, tumor stage, grade, nodal status and histology, and nearest-neighbor and multiple-matching propensity score matched cohorts of bland thrombus vs nonbland thrombus patients were assessed. Multivariable analysis for predictors of cancer-specific survival was performed. From an initial cohort of 579 patients, 446 met inclusion criteria (174 with bland thrombus, 272 without). At baseline, patients with bland thrombus had significantly worse performance status, higher tumor stage, higher prevalence of regional nodal metastases and higher nuclear grade (P < .01 for all). In both nearest-neighbor and multiple-matching propensity score matched cohorts, the presence of bland thrombus presence was associated with inferior median cancer-specific survival (28.1 months vs 156.8 months, and 28.1 months vs 76.7 months, P < .001 for both). The presence of bland thrombus remained independently associated with an increased risk of cancer-specific mortality on multivariable analysis (hazard ratio 4.33, 95% confidence interval 2.79-6.73, P < .001). Presence of bland thrombus is associated with adverse survival outcomes in patients treated surgically for renal tumors with venous tumor thrombus. These findings may have important implications in patient counseling, selection for surgery and inclusion in clinical trials. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Recanalization and flow regulate venous thrombus resolution and Matrix metalloproteinases expression in vivo

    PubMed Central

    Chabasse, Christine; Siefert, Suzanne A.; Chaudry, Mohammed; Hoofnagle, Mark H.; Lal, Brajesh K.; Sarkar, Rajabrata

    2016-01-01

    Objective We examined the role of thrombus recanalization and ongoing blood flow in the process of thrombus resolution by comparing two murine in vivo models of deep venous thrombosis. Design of study In CD1 mice, we performed surgical inferior vena cava (IVC) ligation (stasis thrombosis), stenosis (thrombosis with recanalization) or sham procedure. We analyzed thrombus weight over time as a measure of thrombus resolution, and quantified the mRNA and protein levels of Membrane-Type Matrix Metalloproteinases (MT-MMPs) as well as effectors of the plasmin complex at day 4, 8 and 12 post-surgery. Results Despite similar initial thrombus size, the presence of ongoing blood flow (stenosis model) was associated with a 45.91% subsequent improvement in thrombus resolution at day 8, and 12.57% at day 12, as compared with stasis thrombosis (ligation model). Immunoblot and real-time PCR demonstrated a difference in MMP-2 and MMP-9 activity at day 8 between the two models (P=.03 and P=.006 respectively), as well as a difference in MT2-MMP gene expression at day 8 (P=.044) and day 12 (P=0.03) and MT1-MMP protein expression at day 4 (P=.021). Histological analyses revealed distinct areas of recanalization in the thrombi of the stenosis model compared to the ligation model, as well as the recruitment of inflammatory cells, especially macrophages, and a focal pattern of localized expression of MT1-MMP and MT3-MMP proteins surrounding the areas of recanalization in the stenosis model. Conclusions Recanalization and ongoing blood flow accelerate deep venous thrombus resolution in vivo, and are associated with distinct patterns of MT1- and MT3-MMP expression and macrophages localization in areas of intra-thrombus recanalization. PMID:26993683

  10. Quantifying the mechanical and histological properties of thrombus analog made from human blood for the creation of synthetic thrombus for thrombectomy device testing.

    PubMed

    Merritt, William; Holter, Anne Marie; Beahm, Sharna; Gonzalez, Connor; Becker, Timothy A; Tabor, Aaron; Ducruet, Andrew F; Bonsmann, Laura S; Cotter, Trevor R; Frenklakh, Sergey

    2018-04-25

    Untreated ischemic stroke can lead to severe morbidity and death, and as such, there are numerous endovascular blood-clot removal (thrombectomy) devices approved for human use. Human thrombi types are highly variable and are typically classified in qualitative terms - 'soft/red,' 'hard/white,' or 'aged/calcified.' Quantifying human thrombus properties can accelerate the development of thrombus analogs for the study of thrombectomy outcomes, which are often inconsistent among treated patients. 'Soft'human thrombi were created from blood samples ex vivo (ie, human blood clotted in sample vials) and tested for mechanical properties using a hybrid rheometer material testing system. Synthetic thrombus materials were also mechanically tested and compared with the 'soft' human blood clots. Mechanical testing quantified the shear modulus and dynamic (elastic) modulus of volunteer human thrombus samples. This data was used to formulate a synthetic blood clot made from a composite polymer hydrogel of polyacrylamide and alginate (PAAM-Alg). The PAAM-Alg interpenetrating network of covalently and ionically cross-linked polymers had tunable elastic and shear moduli properties and shape memory characteristics. Due to its adjustable properties, PAAM-Alg can be modified to mimic various thrombi classifications. Future studies will include obtaining and quantitatively classifying patient thrombectomy samples and altering the PAAM-Alg to mimic the results for use with in vitro thrombectomy studies. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  11. Analysis of early thrombus dynamics in a humanized mouse laser injury model.

    PubMed

    Wang, Weiwei; Lindsey, John P; Chen, Jianchun; Diacovo, Thomas G; King, Michael R

    2014-01-01

    Platelet aggregation and thrombus formation at the site of injury is a dynamic process that involves the continuous addition of new platelets as well as thrombus rupture. In the early stages of hemostasis (within minutes after vessel injury) this process can be visualized by transfusing fluorescently labeled human platelets and observing their deposition and detachment. These two counterbalancing events help the developing thrombus reach a steady-state morphology, where it is large enough to cover the injured vessel surface but not too large to form a severe thrombotic occlusion. In this study, the spatial and temporal aspects of early stage thrombus dynamics which result from laser-induced injury on arterioles of cremaster muscle in the humanized mouse were visualized using fluorescent microscopy. It was found that rolling platelets show preference for the upstream region while tethering/detaching platelets were primarily found downstream. It was also determined that the platelet deposition rate is relatively steady, whereas the effective thrombus coverage area does not increase at a constant rate. By introducing a new method to graphically represent the real time in vivo physiological shear stress environment, we conclude that the thrombus continuously changes shape by regional growth and decay, and neither dominates in the high shear stress region.

  12. Recent Inferior Myocardial Infarction Complicated with a Right Ventricular Thrombus Detected by Three Cardiac Imaging Modalities.

    PubMed

    Kuno, Toshiki; Imaeda, Syohei; Hashimoto, Kenji; Ryuzaki, Toshinobu; Saito, Tetsuya; Yamazaki, Hiroyuki; Tabei, Ryota; Kodaira, Masaki; Hase, Manabu; Numasawa, Yohei

    2018-03-01

    We report the case of a 71-year-old woman diagnosed with recent inferior myocardial infarction complicated with right ventricular infarction and a right ventricular thrombus. Three-dimensional transthoracic echocardiography, contrast-enhanced computed tomography, and cardiac magnetic resonance imaging clearly detected a thrombus. We consider cases with a recent right ventricular infarction to require assessment for thrombus formations in the right ventricle. Fortunately, vigorous anticoagulation therapy resolved the thrombi in both the right ventricle and right coronary artery.

  13. Thrombus aspiration catheter is a Dottering balloon.

    PubMed

    Sheshagiri Rao, D; Barik, Ramachandra; Prasad, Akula Siva

    2016-01-01

    Coronary angiogram in a young man with history of STEMI with delayed presentation revealed subtotal occlusion of left anterior descending artery (LAD) with large thrombotic filling defect distal to the critical lesion. PCI was preferred without delay because of ongoing chest pain. Several runs of thrombus aspiration failed to detect any visible thrombus. However, the immediate angiogram after thrombus aspiration showed complete distal embolization of the thrombus which could have been achieved by Dottering or balloon dilatation. In contrary to the general perception, does thrombus aspiration push more thrombus than it can aspirate? Copyright © 2016 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

  14. Recanalization and flow regulate venous thrombus resolution and matrix metalloproteinase expression in vivo.

    PubMed

    Chabasse, Christine; Siefert, Suzanne A; Chaudry, Mohammed; Hoofnagle, Mark H; Lal, Brajesh K; Sarkar, Rajabrata

    2015-01-01

    We examined the role of thrombus recanalization and ongoing blood flow in the process of thrombus resolution by comparing two murine in vivo models of deep venous thrombosis. In CD1 mice, we performed surgical inferior vena cava ligation (stasis thrombosis), stenosis (thrombosis with recanalization), or sham procedure. We analyzed thrombus weight over time as a measure of thrombus resolution and quantified the messenger RNA and protein levels of membrane-type matrix metalloproteinases (MT-MMPs) as well as effectors of the plasmin complex at days 4, 8, and 12 after surgery. Despite similar initial thrombus size, the presence of ongoing blood flow (stenosis model) was associated with a 45.91% subsequent improvement in thrombus resolution at day 8 and 12.57% at day 12 compared with stasis thrombosis (ligation model). Immunoblot and real-time polymerase chain reaction analysis demonstrated a difference in MMP-2 and MMP-9 activity at day 8 between the two models (P = .03 and P = .006, respectively) as well as a difference in MT2-MMP gene expression at day 8 (P = .044) and day 12 (P = .03) and MT1-MMP protein expression at day 4 (P = .021). Histologic analyses revealed distinct areas of recanalization in the thrombi of the stenosis model compared with the ligation model as well as the recruitment of inflammatory cells, especially macrophages, and a focal pattern of localized expression of MT1-MMP and MT3-MMP proteins surrounding the areas of recanalization in the stenosis model. Recanalization and ongoing blood flow accelerate deep venous thrombus resolution in vivo and are associated with distinct patterns of MT1-MMP and MT3-MMP expression and macrophage localization in areas of intrathrombus recanalization. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  15. Impaired left ventricular diastolic function is related to the formation of left ventricular apical thrombus in patients with acute anterior myocardial infarction.

    PubMed

    Choi, Ung Lim; Park, Jae-Hyeong; Sun, Byung Joo; Oh, Jin Kyung; Seong, Seok Woo; Lee, Jae-Hwan; Choi, Si Wan; Jeong, Jin-Ok; Kwon, In Sun; Seong, In-Whan

    2018-05-01

    Left ventricular (LV) apical thrombus is a clinically important complication which can cause systemic embolization in patients with anterior acute myocardial infarction (AMI). Systolic dysfunction has been a risk factor for developing LV apical thrombus in AMI patients. However, the role of diastolic dysfunction in the development of LV apical thrombus in these patients is still unknown. We performed this study to evaluate whether diastolic dysfunction can influence the development of LV apical thrombus in anterior AMI patients. We retrospectively analyzed all consecutive anterior AMI patients with available echocardiographic images within 1 month from January 2005 to April 2016. After gathering clinical characteristics from their medical records, systolic and diastolic functions were analyzed from digitally stored echocardiographic images. We included a total of 1045 patients (748 males, mean age 64 ± 12 years) with anterior AMI, and 494 (47%) were diagnosed as STEMI. The incidence of LV apical thrombus was 3.3% (34/1045). The LV apical thrombus group had larger LV diastolic dimension, larger LV diastolic and systolic volumes, and lower LVEF than the no LV thrombus group. The LV apical thrombus group showed higher mitral E velocity over mitral annular E' velocity ratio, an indicator of LV end-diastolic pressure (P < 0.001). In the LV apical thrombus group, the incidence of grade 2 diastolic dysfunction (32 vs 12%, P = 0.001) and grade 3 diastolic dysfunction (26 vs 2%, P < 0.001) were significantly higher than in the no LV apical thrombus group. The presence of more than grade 2 diastolic dysfunction, LVEF and presence of LV apical aneurysm were statistically significant factors associated with LV apical thrombus after the multivariate analysis. In conclusion, along with LV systolic dysfunction and LV apical aneurysm, LV diastolic dysfunction was also related with the presence of LV apical thrombus in patients with anterior AMI.

  16. Roles of platelet STIM1 and Orai1 in glycoprotein VI- and thrombin-dependent procoagulant activity and thrombus formation.

    PubMed

    Gilio, Karen; van Kruchten, Roger; Braun, Attila; Berna-Erro, Alejandro; Feijge, Marion A H; Stegner, David; van der Meijden, Paola E J; Kuijpers, Marijke J E; Varga-Szabo, David; Heemskerk, Johan W M; Nieswandt, Bernhard

    2010-07-30

    In platelets, STIM1 has been recognized as the key regulatory protein in store-operated Ca(2+) entry (SOCE) with Orai1 as principal Ca(2+) entry channel. Both proteins contribute to collagen-dependent arterial thrombosis in mice in vivo. It is unclear whether STIM2 is involved. A key platelet response relying on Ca(2+) entry is the surface exposure of phosphatidylserine (PS), which accomplishes platelet procoagulant activity. We studied this response in mouse platelets deficient in STIM1, STIM2, or Orai1. Upon high shear flow of blood over collagen, Stim1(-/-) and Orai1(-/-) platelets had greatly impaired glycoprotein (GP) VI-dependent Ca(2+) signals, and they were deficient in PS exposure and thrombus formation. In contrast, Stim2(-/-) platelets reacted normally. Upon blood flow in the presence of thrombin generation and coagulation, Ca(2+) signals of Stim1(-/-) and Orai1(-/-) platelets were partly reduced, whereas the PS exposure and formation of fibrin-rich thrombi were normalized. Washed Stim1(-/-) and Orai1(-/-) platelets were deficient in GPVI-induced PS exposure and prothrombinase activity, but not when thrombin was present as co-agonist. Markedly, SKF96365, a blocker of (receptor-operated) Ca(2+) entry, inhibited Ca(2+) and procoagulant responses even in Stim1(-/-) and Orai1(-/-) platelets. These data show for the first time that: (i) STIM1 and Orai1 jointly contribute to GPVI-induced SOCE, procoagulant activity, and thrombus formation; (ii) a compensating Ca(2+) entry pathway is effective in the additional presence of thrombin; (iii) platelets contain two mechanisms of Ca(2+) entry and PS exposure, only one relying on STIM1-Orai1 interaction.

  17. Flow Residence Time and Regions of Intraluminal Thrombus Deposition in Intracranial Aneurysms

    PubMed Central

    Boussel, L.; Ge, L.; Leach, J. R.; Martin, A. J.; Lawton, M. T.; McCulloch, C.; Saloner, D.

    2010-01-01

    Thrombus formation in intracranial aneurysms, while sometimes stabilizing lesion growth, can present additional risk of thrombo-embolism. The role of hemodynamics in the progression of aneurysmal disease can be elucidated by patient-specific computational modeling. In our previous work, patient-specific computational fluid dynamics (CFD) models were constructed from MRI data for three patients who had fusiform basilar aneurysms that were thrombus-free and then proceeded to develop intraluminal thrombus. In this study, we investigated the effect of increased flow residence time (RT) by modeling passive scalar advection in the same aneurysmal geometries. Non-Newtonian pulsatile flow simulations were carried out in base-line geometries and a new postprocessing technique, referred to as “virtual ink” and based on the passive scalar distribution maps, was used to visualize the flow and estimate the flow RT. The virtual ink technique clearly depicted regions of flow separation. The flow RT at different locations adjacent to aneurysmal walls was calculated as the time the virtual ink scalar remained above a threshold value. The RT values obtained in different areas were then correlated with the location of intra-aneurysmal thrombus observed at a follow-up MR study. For each patient, the wall shear stress (WSS) distribution was also obtained from CFD simulations and correlated with thrombus location. The correlation analysis determined a significant relationship between regions where CFD predicted either an increased RT or low WSS and the regions where thrombus deposition was observed to occur in vivo. A model including both low WSS and increased RT predicted thrombus-prone regions significantly better than the models with RT or WSS alone. PMID:20499185

  18. Defective angiogenesis delays thrombus resolution: a potential pathogenetic mechanism underlying chronic thromboembolic pulmonary hypertension

    PubMed Central

    Panzenboeck, Adelheid; Winter, Max P; Schubert, Uwe; Voswinckel, Robert; Frey, Maria K; Jakowitsch, Johannes; Alimohammadi, Arman; Hobohm, Lukas; Mangold, Andreas; Bergmeister, Helga; Sibilia, Maria; Wagner, Erwin F; Mayer, Eckhard; Klepetko, Walter; Hoelzenbein, Thomas J; Preissner, Klaus T; Lang, Irene M

    2015-01-01

    Objective Restoration of patency is a natural target of vascular remodeling following venous thrombosis that involves vascular endothelial cells and smooth muscle cells as well as leukocytes. Acute pulmonary emboli usually resolve within six months. However, in some instances, thrombi transform into fibrous vascular obstructions, resulting in occlusion of the deep veins, or in chronic thromboembolic pulmonary hypertension (CTEPH). We proposed that dysregulated thrombus angiogenesis may contribute to thrombus persistence. Approach and Results Mice with an endothelial-cell-specific conditional deletion of vascular endothelial growth factor receptor 2/kinase insert domain protein receptor (VEGF-R2/Kdr) were utilized in a model of stagnant flow venous thrombosis closely resembling human deep vein thrombosis. Biochemical and functional analyses were performed on pulmonary endarterectomy specimens from patients with CTEPH, a human model of non-resolving venous thromboembolism. Endothelial cell-specific deletion of Kdr and subsequent ablation of thrombus vascularization delayed thrombus resolution. In accordance with these findings, organized human CTEPH thrombi were largely devoid of vascular structures. Several vessel-specific genes such as KDR, vascular endothelial cadherin and podoplanin were expressed at lower levels in white CTEPH thrombi than in organizing deep vein thrombi and organizing thrombi from aortic aneurysms. In addition, red CTEPH thrombi attenuated the angiogenic response induced by VEGF. Conclusions In the present work, we propose a mechanism of thrombus non-resolution demonstrating that endothelial cell-specific deletion of Kdr abates thrombus vessel formation, misguiding thrombus resolution. Medical conditions associated with the development of CTEPH may be compromising early thrombus angiogenesis. PMID:24526692

  19. A Case of Myopathy, Encephalopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS) Syndrome with Intracardiac Thrombus [corrected].

    PubMed

    Joo, Jung-Chul; Seol, Myung Do; Yoon, Jin Won; Lee, Young Soo; Kim, Dong-Keun; Choi, Yong Hoon; Ahn, Hyo Seong; Cho, Wook Hyun

    2013-03-01

    Myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) is a multisystem clinical syndrome manifested by mitochondrial myopathy, encephalopathy, lactic acidosis and recurrent stroke-like episodes. A 27-year-old female with MELAS syndrome presented with cerebral infarction. Echocardiography revealed a thrombus attached to the apex of the hypertrophied left ventricle, with decreased systolic function. The embolism of the intracardiac thrombus might have been the cause of stroke. There should be more consideration given to the increased possibility of intracardiac thrombus formation when a MELAS patient with cardiac involvement is encountered.

  20. A Thrombus Generation Model Applied to Aneurysms Treated with Shape Memory Polymer Foam and Metal Coils

    NASA Astrophysics Data System (ADS)

    Horn, John; Ortega, Jason; Hartman, Jonathan; Maitland, Duncan

    2015-11-01

    To prevent their rupture, intracranial aneurysms are often treated with endovascular metal coils which fill the aneurysm sac and isolate it from the arterial flow. Despite its widespread use, this method can result in suboptimal outcomes leading to aneurysm recurrence. Recently, shape memory polymer foam has been proposed as an alternative aneurysm filler. In this work, a computational model has been developed to predict thrombus formation in blood in response to such cardiovascular implantable devices. The model couples biofluid and biochemical phenomena present as the blood interacts with a device and stimulates thrombus formation. This model is applied to simulations of both metal coil and shape memory polymer foam treatments within an idealized 2D aneurysm geometry. Using the predicted thrombus responses, the performance of these treatments is evaluated and compared. The results suggest that foam-treated aneurysms may fill more quickly and more completely with thrombus than coil-filled aneurysms, potentially leading to improved long-term aneurysm healing. This work was performed in part under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

  1. Measurement of Thrombus Flux Using Transesophageal Echocardiography

    NASA Astrophysics Data System (ADS)

    Yamaguchi, Tadashi; Hirai, Kazuki; Aoki, Masami; Miyagi, Jin; Suzuki, Masahiko; Moriya, Hideshige; Hachiya, Hiroyuki

    2006-05-01

    Deep venous thrombosis (DVT) and pulmonary thromboembolism (PTE) are serious problem of total knee replacement (TKR). These diseases may be caused by a thrombus formed during the TKR operation. Therefore, understanding the flow volume of thrombus is important for curing and preventing PTE. In this paper, we tried to understanding the situation of the flow of thrombus by using transesophageal echocardiography movies. We applied the signal processing technique the FSET to extract the anomalous information from ultrasonic echo image. As a result of processing, the time change of the flow volume of thrombus was confirmed.

  2. Roles of Platelet STIM1 and Orai1 in Glycoprotein VI- and Thrombin-dependent Procoagulant Activity and Thrombus Formation*

    PubMed Central

    Gilio, Karen; van Kruchten, Roger; Braun, Attila; Berna-Erro, Alejandro; Feijge, Marion A. H.; Stegner, David; van der Meijden, Paola E. J.; Kuijpers, Marijke J. E.; Varga-Szabo, David; Heemskerk, Johan W. M.; Nieswandt, Bernhard

    2010-01-01

    In platelets, STIM1 has been recognized as the key regulatory protein in store-operated Ca2+ entry (SOCE) with Orai1 as principal Ca2+ entry channel. Both proteins contribute to collagen-dependent arterial thrombosis in mice in vivo. It is unclear whether STIM2 is involved. A key platelet response relying on Ca2+ entry is the surface exposure of phosphatidylserine (PS), which accomplishes platelet procoagulant activity. We studied this response in mouse platelets deficient in STIM1, STIM2, or Orai1. Upon high shear flow of blood over collagen, Stim1−/− and Orai1−/− platelets had greatly impaired glycoprotein (GP) VI-dependent Ca2+ signals, and they were deficient in PS exposure and thrombus formation. In contrast, Stim2−/− platelets reacted normally. Upon blood flow in the presence of thrombin generation and coagulation, Ca2+ signals of Stim1−/− and Orai1−/− platelets were partly reduced, whereas the PS exposure and formation of fibrin-rich thrombi were normalized. Washed Stim1−/− and Orai1−/− platelets were deficient in GPVI-induced PS exposure and prothrombinase activity, but not when thrombin was present as co-agonist. Markedly, SKF96365, a blocker of (receptor-operated) Ca2+ entry, inhibited Ca2+ and procoagulant responses even in Stim1−/− and Orai1−/− platelets. These data show for the first time that: (i) STIM1 and Orai1 jointly contribute to GPVI-induced SOCE, procoagulant activity, and thrombus formation; (ii) a compensating Ca2+ entry pathway is effective in the additional presence of thrombin; (iii) platelets contain two mechanisms of Ca2+ entry and PS exposure, only one relying on STIM1-Orai1 interaction. PMID:20519511

  3. First Selective 12-LOX Inhibitor, ML355, Impairs Thrombus Formation and Vessel Occlusion In Vivo With Minimal Effects on Hemostasis.

    PubMed

    Adili, Reheman; Tourdot, Benjamin E; Mast, Katherine; Yeung, Jennifer; Freedman, John C; Green, Abigail; Luci, Diane K; Jadhav, Ajit; Simeonov, Anton; Maloney, David J; Holman, Theodore R; Holinstat, Michael

    2017-10-01

    Adequate platelet reactivity is required for maintaining hemostasis. However, excessive platelet reactivity can also lead to the formation of occlusive thrombi. Platelet 12(S)-lipoxygenase (12-LOX), an oxygenase highly expressed in the platelet, has been demonstrated to regulate platelet function and thrombosis ex vivo, supporting a key role for 12-LOX in the regulation of in vivo thrombosis. However, the ability to pharmacologically target 12-LOX in vivo has not been established to date. Here, we studied the effect of the first highly selective 12-LOX inhibitor, ML355, on in vivo thrombosis and hemostasis. ML355 dose-dependently inhibited human platelet aggregation and 12-LOX oxylipin production, as confirmed by mass spectrometry. Interestingly, the antiplatelet effects of ML355 were reversed after exposure to high concentrations of thrombin in vitro. Ex vivo flow chamber assays confirmed that human platelet adhesion and thrombus formation at arterial shear over collagen were attenuated in whole blood treated with ML355 comparable to aspirin. Oral administration of ML355 in mice showed reasonable plasma drug levels by pharmacokinetic assessment. ML355 treatment impaired thrombus growth and vessel occlusion in FeCl 3 -induced mesenteric and laser-induced cremaster arteriole thrombosis models in mice. Importantly, hemostatic plug formation and bleeding after treatment with ML355 was minimal in mice in response to laser ablation on the saphenous vein or in a cremaster microvasculature laser-induced rupture model. Our data strongly support 12-LOX as a key determinant of platelet reactivity in vivo, and inhibition of platelet 12-LOX with ML355 may represent a new class of antiplatelet therapy. © 2017 American Heart Association, Inc.

  4. Clinical Sequelae of Thrombus in an Inferior Vena Cava Filter

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ahmad, Iftikhar; Yeddula, Kalpana; Wicky, Stephan

    The purpose of this study was to assess the long-term clinical sequelae of inferior vena cava (IVC) filter thrombus and the effect of anticoagulation on filter thrombus. Of 1,718 patients who had IVC filters placed during 2001-2008, 598 (34.8%) had follow-up abdominal CT. Filter thrombus was seen in 111 of the 598 (18.6%). There were 44 men (39.6%). The mean age at filter placement was 64 years. The medical diseases included cancer in 64, trauma in 15, stroke in 12, and others in 20. The frequency of filter thrombus on CT and asymptomatic filter thrombus on CT was calculated. Themore » frequency of pulmonary embolism (PE) in patients with filter thrombus was calculated. The frequency of thrombus progression or regression (on CT, available in 56) was calculated. The effect of anticoagulation on filter thrombus regression/progression was evaluated using the Fisher exact test by comparing the group of patients who received anticoagulants versus those who did not. A P-value of <0.05 was considered significant. The overall frequency of filter thrombus was 18.6%. Total occlusion of the IVC filter was seen in 12 of 598 (2%). The filter thrombus was asymptomatic in 110 (18.3%). Filter thrombus was detected after a median of 35 days (range, 0-2082) following filter placement. Thrombus extended above the filter in 4 (3.6%); IVC thrombus below the filter was seen in 35(31.5%). Thrombus in the filter occluded <25% of the filter volume in 58 (52.3%), 25-50% in 21 (18.9%), and 50-75% in 20 (18%). Total IVC occlusion was seen in 12 (10.8%). Eighty-three patients received anticoagulation. Sixteen patients developed symptoms of PE. PE was confirmed on CT in 3 of 15 (2.7%). On follow-up, filter thrombus regressed completely in 19 (33.9%) after a median of 6 months. Filter thrombus decreased in size in 13 (23.2%) and it progressed without IVC occlusion in 7 (12.6%). In one (1.7%), filter thrombus progressed to IVC occlusion. Filter thrombus remained stable in 16 (28.6%). There was

  5. Tocotrienols-induced inhibition of platelet thrombus formation and platelet aggregation in stenosed canine coronary arteries.

    PubMed

    Qureshi, Asaf A; Karpen, Charles W; Qureshi, Nilofer; Papasian, Christopher J; Morrison, David C; Folts, John D

    2011-04-14

    Dietary supplementation with tocotrienols has been shown to decrease the risk of coronary artery disease. Tocotrienols are plant-derived forms of vitamin E, which have potent anti-inflammatory, antioxidant, anticancer, hypocholesterolemic, and neuroprotective properties. Our objective in this study was to determine the extent to which tocotrienols inhibit platelet aggregation and reduce coronary thrombosis, a major risk factor for stroke in humans. The present study was carried out to determine the comparative effects of α-tocopherol, α-tocotrienol, or tocotrienol rich fraction (TRF; a mixture of α-+γ-+δ-tocotrienols) on in vivo platelet thrombosis and ex vivo platelet aggregation (PA) after intravenous injection in anesthetized dogs, by using a mechanically stenosed circumflex coronary artery model (Folts' cyclic flow model). Collagen-induced platelet aggregation (PA) in platelet rich plasma (PRP) was decreased markedly after treatment with α-tocotrienol (59%; P<0.001) and TRF (92%; P<0.001). α-Tocopherol treatment was less effective, producing only a 22% (P<0.05) decrease in PA. Adenosine diphosphate-induced (ADP) PA was also decreased after treatment with α-tocotrienol (34%; P<0.05) and TRF (42%; P<0.025). These results also indicate that intravenously administered tocotrienols were significantly better than tocopherols in inhibiting cyclic flow reductions (CFRs), a measure of the acute platelet-mediated thrombus formation. Tocotrienols (TRF) given intravenously (10 mg/kg), abolished CFRs after a mean of 68 min (range 22 -130 min), and this abolition of CFRs was sustained throughout the monitoring period (50-160 min).Next, pharmacokinetic studies were carried out and tocol levels in canine plasma and platelets were measured. As expected, α-Tocopherol treatment increased levels of total tocopherols in post- vs pre-treatment specimens (57 vs 18 μg/mL in plasma, and 42 vs 10 μg/mL in platelets). However, treatment with α-tocopherol resulted in slightly

  6. Tocotrienols-induced inhibition of platelet thrombus formation and platelet aggregation in stenosed canine coronary arteries

    PubMed Central

    2011-01-01

    Background Dietary supplementation with tocotrienols has been shown to decrease the risk of coronary artery disease. Tocotrienols are plant-derived forms of vitamin E, which have potent anti-inflammatory, antioxidant, anticancer, hypocholesterolemic, and neuroprotective properties. Our objective in this study was to determine the extent to which tocotrienols inhibit platelet aggregation and reduce coronary thrombosis, a major risk factor for stroke in humans. The present study was carried out to determine the comparative effects of α-tocopherol, α-tocotrienol, or tocotrienol rich fraction (TRF; a mixture of α- + γ- + δ-tocotrienols) on in vivo platelet thrombosis and ex vivo platelet aggregation (PA) after intravenous injection in anesthetized dogs, by using a mechanically stenosed circumflex coronary artery model (Folts' cyclic flow model). Results Collagen-induced platelet aggregation (PA) in platelet rich plasma (PRP) was decreased markedly after treatment with α-tocotrienol (59%; P < 0.001) and TRF (92%; P < 0.001). α-Tocopherol treatment was less effective, producing only a 22% (P < 0.05) decrease in PA. Adenosine diphosphate-induced (ADP) PA was also decreased after treatment with α-tocotrienol (34%; P < 0.05) and TRF (42%; P < 0.025). These results also indicate that intravenously administered tocotrienols were significantly better than tocopherols in inhibiting cyclic flow reductions (CFRs), a measure of the acute platelet-mediated thrombus formation. Tocotrienols (TRF) given intravenously (10 mg/kg), abolished CFRs after a mean of 68 min (range 22 -130 min), and this abolition of CFRs was sustained throughout the monitoring period (50 - 160 min). Next, pharmacokinetic studies were carried out and tocol levels in canine plasma and platelets were measured. As expected, α-Tocopherol treatment increased levels of total tocopherols in post- vs pre-treatment specimens (57 vs 18 μg/mL in plasma, and 42 vs 10 μg/mL in platelets). However, treatment with

  7. A Relation Between Near-Wall Particle-Hemodynamics and Onset of Thrombus Formation in Abdominal Aortic Aneurysms

    PubMed Central

    Basciano, C.; Kleinstreuer, C.; Hyun, S.; Finol, E. A.

    2014-01-01

    A novel computational particle-hemodynamics analysis of key criteria for the onset of an intraluminal thrombus (ILT) in a patient-specific abdominal aortic aneurysm (AAA) is presented. The focus is on enhanced platelet and white blood cell residence times as well as their elevated surface-shear loads in near-wall regions of the AAA sac. The generalized results support the hypothesis that a patient's AAA geometry and associated particle-hemodynamics have the potential to entrap activated blood particles, which will play a role in the onset of ILT. Although the ILT history of only a single patient was considered, the modeling and simulation methodology provided allow for the development of an efficient computational tool to predict the onset of ILT formation in complex patient-specific cases. PMID:21373952

  8. A large left ventricular thrombus.

    PubMed

    Patanè, Salvatore; Marte, Filippo

    2009-06-26

    The discovery of a left ventricular mass obliges the clinician to perform a differential diagnosis including tumour or lipoma versus thrombus and its assessment presents important clinical implications. Dilated cardiomyopathy has been associated with left ventricular thrombosis which leads to substantial morbidity and mortality as a site for peripheral emboli. There are some studies on patients with dilated cardiomyopathy showing altered hemostasis and platelet behavior despite sinus rhythm. An increased incidence of thromboembolism is also well recognized in patients with left ventricular systolic dysfunction complicating history of myocardial infarction. Clinical dilemmas in treating left ventricular thrombus have been described too. We present a case of a large mobile left ventricular thrombus in a 71-year-old Italian man with dilated cardiomyopathy and history of myocardial infarction.

  9. Catching a floating thrombus; a case report on the treatment of a large thrombus in the ascending aorta.

    PubMed

    de Maat, Gijs Eduard; Vigano, Giorgio; Mariani, Massimo Alessandro; Natour, Ehsan

    2017-05-19

    The ascending aorta is an uncommon site for non-infective thrombus. In non-aneurysmal and non-atherosclerotic vessels this condition becomes extremely rare, while it represents a source of potential cerebral and peripheral embolic events. Currently, there is no consensus in the guidelines on how to treat a free floating thrombus in ascending aorta, therefore we present our decision making process and therapeutic strategy. A healthy 48-year-old man was hospital admitted with acute abdominal pain. CT-scan showed a right renal embolism in presence of a defect in the distal ascending aorta suggestive for thrombus. After heart team discussion the patient was scheduled for surgery and successfully underwent an emergent thrombus removal. Also, owing to multiple aortic wall insertions, the ascending aorta was replaced. The patient's recovery was uneventful and histological examination showed no signs of connective tissue disorders of aortic wall while confirmed the thrombotic nature of the mass. We present a patient with a floating thrombus in the ascending aorta who underwent an ascending aorta replacement. While angio-CT scan led to a prompt diagnosis, intraoperative epi-aortic echocardiography allowed to define precise location of thrombus, minimizing operative risk. This case demonstrates that multi-disciplinary heart team discussion is essential to define a successful strategy, that surgical treatment is feasible with specific tools such as epi-aortic echocardiography.

  10. Multi-physics 3D computational study of leaflet thrombus formation following surgical and transcatheter aortic valve replacement

    NASA Astrophysics Data System (ADS)

    Vahidkhah, Koohyar; Abbasi, Mostafa; Barakat, Mohammed; Dvir, Danny; Azadani, Ali

    2017-11-01

    An increasingly recognized complication following surgical/transcatheter aortic valve replacement is thrombosis or blood clot formation on replacement valve leaflets. A predisposing factor in thrombus formation on biomaterial surfaces of a bioprosthetic heart valve is blood stasis. Longer residence time of blood provides an opportunity for platelets and agonists to accumulate to critical concentrations that leads to platelet activation and then thrombosis. In this study, we have developed a fluid-solid interaction (FSI) modeling approach, to quantify blood stasis on the leaflets of bioprosthetic aortic valves with different design operating in a patient-specific geometry. We have validated our FSI model against experimental measurements of valve opening/closing as well as in-vitro particle image velocimetry. We have also embedded in our method a model for transport of platelets and agonists (ADP, TxA2, and thrombin) and their interactions that result in platelets activation and adhesion to biomaterial bioprosthetic surfaces. We have provided quantitative evidence for the correlation between long residence of blood on bioprosthetic aortic valve leaflets and formation of high thrombogenicity risk regions on the leaflets that are characterized by accumulation of activated platelet.

  11. Parmodulins inhibit thrombus formation without inducing endothelial injury caused by vorapaxar.

    PubMed

    Aisiku, Omozuanvbo; Peters, Christian G; De Ceunynck, Karen; Ghosh, Chandra C; Dilks, James R; Fustolo-Gunnink, Susanna F; Huang, Mingdong; Dockendorff, Chris; Parikh, Samir M; Flaumenhaft, Robert

    2015-03-19

    Protease-activated receptor-1 (PAR1) couples the coagulation cascade to platelet activation during myocardial infarction and to endothelial inflammation during sepsis. This receptor demonstrates marked signaling bias. Its activation by thrombin stimulates prothrombotic and proinflammatory signaling, whereas its activation by activated protein C (APC) stimulates cytoprotective and antiinflammatory signaling. A challenge in developing PAR1-targeted therapies is to inhibit detrimental signaling while sparing beneficial pathways. We now characterize a novel class of structurally unrelated small-molecule PAR1 antagonists, termed parmodulins, and compare the activity of these compounds to previously characterized compounds that act at the PAR1 ligand-binding site. We find that parmodulins target the cytoplasmic face of PAR1 without modifying the ligand-binding site, blocking signaling through Gαq but not Gα13 in vitro and thrombus formation in vivo. In endothelium, parmodulins inhibit prothrombotic and proinflammatory signaling without blocking APC-mediated pathways or inducing endothelial injury. In contrast, orthosteric PAR1 antagonists such as vorapaxar inhibit all signaling downstream of PAR1. Furthermore, exposure of endothelial cells to nanomolar concentrations of vorapaxar induces endothelial cell barrier dysfunction and apoptosis. These studies demonstrate how functionally selective antagonism can be achieved by targeting the cytoplasmic face of a G-protein-coupled receptor to selectively block pathologic signaling while preserving cytoprotective pathways. © 2015 by The American Society of Hematology.

  12. RhoG protein regulates platelet granule secretion and thrombus formation in mice.

    PubMed

    Goggs, Robert; Harper, Matthew T; Pope, Robert J; Savage, Joshua S; Williams, Christopher M; Mundell, Stuart J; Heesom, Kate J; Bass, Mark; Mellor, Harry; Poole, Alastair W

    2013-11-22

    Rho GTPases such as Rac, RhoA, and Cdc42 are vital for normal platelet function, but the role of RhoG in platelets has not been studied. In other cells, RhoG orchestrates processes integral to platelet function, including actin cytoskeletal rearrangement and membrane trafficking. We therefore hypothesized that RhoG would play a critical role in platelets. Here, we show that RhoG is expressed in human and mouse platelets and is activated by both collagen-related peptide (CRP) and thrombin stimulation. We used RhoG(-/-) mice to study the function of RhoG in platelets. Integrin activation and aggregation were reduced in RhoG(-/-) platelets stimulated by CRP, but responses to thrombin were normal. The central defect in RhoG(-/-) platelets was reduced secretion from α-granules, dense granules, and lysosomes following CRP stimulation. The integrin activation and aggregation defects could be rescued by ADP co-stimulation, indicating that they are a consequence of diminished dense granule secretion. Defective dense granule secretion in RhoG(-/-) platelets limited recruitment of additional platelets to growing thrombi in flowing blood in vitro and translated into reduced thrombus formation in vivo. Interestingly, tail bleeding times were normal in RhoG(-/-) mice, suggesting that the functions of RhoG in platelets are particularly relevant to thrombotic disorders.

  13. Hemodynamics-Driven Deposition of Intraluminal Thrombus in Abdominal Aortic Aneurysms

    PubMed Central

    Di Achille, P.; Tellides, G.; Humphrey, J.D.

    2016-01-01

    Accumulating evidence suggests that intraluminal thrombus plays many roles in the natural history of abdominal aortic aneurysms. There is, therefore, a pressing need for computational models that can describe and predict the initiation and progression of thrombus in aneurysms. In this paper, we introduce a phenomenological metric for thrombus deposition potential and use hemodynamic simulations based on medical images from six patients to identify best-fit values of the two key model parameters. We then introduce a shape optimization method to predict the associated radial growth of the thrombus into the lumen based on the expectation that thrombus initiation will create a thrombogenic surface, which in turn will promote growth until increasing hemodynamically induced frictional forces prevent any further cell or protein deposition. Comparisons between predicted and actual intraluminal thrombus in the six patient-specific aneurysms suggest that this phenomenological description provides a good first estimate of thrombus deposition. We submit further that, because the biologically active region of the thrombus appears to be confined to a thin luminal layer, predictions of morphology alone may be sufficient to inform fluid-solid-growth models of aneurysmal growth and remodeling. PMID:27569676

  14. Comparison of the effect of dabigatran and dalteparin on thrombus stability in a murine model of venous thromboembolism.

    PubMed

    Shaya, S A; Saldanha, L J; Vaezzadeh, N; Zhou, J; Ni, R; Gross, P L

    2016-01-01

    ESSENTIALS: Does thrombus stability alter the presentation of venous thromboembolism and do anticoagulants alter this? In a murine model, we imaged a femoral vein thrombus and quantified emboli in the pulmonary arteries. Dabigatran decreases thrombus stability via factor XIII increasing embolization and pulmonary emboli. This cautions against the unapproved use of dabigatran for acute initial treatment of deep vein thrombosis. Venous thromboembolism (VTE) is a collective term for deep vein thrombosis (DVT) and pulmonary embolism (PE). Thrombus instability possibly contributes to progression of DVT to PE, and direct thrombin inhibitors (DTIs) may alter this. To develop a model to assess thrombus stability and its link to PE burden, and identify whether DTIs, in contrast to low-molecular-weight heparin (LMWH), alter this correlation. Twelve minutes after ferric chloride-induced thrombus formation in the femoral vein of female mice, saline, dalteparin (LMWH) or dabigatran (DTI) was administered. Thrombus size and embolic events breaking off from the thrombus were quantified before treatment and at 10-min intervals after treatment for 2 h using intravital videomicroscopy. Lungs were stained for the presence of PE. Thrombus size was similar over time and between treatment groups. Total and large embolic events and pulmonary emboli were highest after treatment with dabigatran. Variations in amounts of pulmonary embolic events were not attributed to variations in thrombus size. Large embolic events correlated with the number of emboli per lung slice independent of treatment. Embolization in factor XIII deficient (FXIII(-/-) ) saline-treated mice was greater than that in wild-type (WT) saline-treated mice, but was similar to WT dabigatran-treated mice. We have developed a mouse model of VTE that can quantify emboli and correlate this with PE burden. Consistent with clinical data, dabigatran, a DTI, acutely decreases thrombus stability and increases PE burden compared with

  15. Prediction of thrombus-related mechanical prosthetic valve dysfunction using transesophageal echocardiography

    NASA Technical Reports Server (NTRS)

    Lin, S. S.; Tiong, I. Y.; Asher, C. R.; Murphy, M. T.; Thomas, J. D.; Griffin, B. P.

    2000-01-01

    Identification of thrombus-related mechanical prosthetic valve dysfunction (MPVD) has important therapeutic implications. We sought to develop an algorithm, combining clinical and echocardiographic parameters, for prediction of thrombus-related MPVD in a series of 53 patients (24 men, age 52 +/- 16 years) who had intraoperative diagnosis of thrombus or pannus from 1992 to 1997. Clinical and echocardiographic parameters were analyzed to identify predictors of thrombus and pannus. Prevalence of thrombus and diagnostic yields relative to the number of predictors were determined. There were 22 patients with thrombus, 19 patients with pannus, and 12 patients with both. Forty-two of 53 masses were visualized using transesophageal echocardiography (TEE), including 29 of 34 thrombi or both thrombi and panni and 13 of 19 isolated panni. Predictors of thrombus or mixed presentation include mobile mass (p = 0.009), attachment to occluder (p = 0.02), elevated gradients (p = 0.04), and an international normalized ratio of < or = 2.5 (p = 0.03). All 34 patients with thrombus or mixed presentation had > or = 1 predictor. The prevalence of thrombus in the presence of < or = 1, 2, and > or = 3 predictors is 14%, 69%, and 91%, respectively. Thus, TEE is sensitive in the identification of abnormal mass in the setting of MPVD. An algorithm based on clinical and transesophageal echocardiographic predictors may be useful to estimate the likelihood of thrombus in the setting of MPVD. In the presence of > or = 3 predictors, the probability of thrombus is high.

  16. Magnetic Resonance T1 Relaxation Time of Venous Thrombus Is Determined by Iron Processing and Predicts Susceptibility to Lysis

    PubMed Central

    Modarai, Bijan; Blume, Ulrike; Humphries, Julia; Patel, Ashish S.; Phinikaridou, Alkystis; Evans, Colin E.; Mattock, Katherine; Grover, Steven P.; Ahmad, Anwar; Lyons, Oliver T.; Attia, Rizwan Q.; Renné, Thomas; Premaratne, Sobath; Wiethoff, Andrea J.; Botnar, René M.; Schaeffter, Tobias; Waltham, Matthew; Smith, Alberto

    2014-01-01

    Background The magnetic resonance longitudinal relaxation time (T1) changes with thrombus age in humans. In this study, we investigate the possible mechanisms that give rise to the T1 signal in venous thrombi and whether changes in T1 relaxation time are informative of the susceptibility to lysis. Methods and Results Venous thrombosis was induced in the vena cava of BALB/C mice, and temporal changes in T1 relaxation time correlated with thrombus composition. The mean T1 relaxation time of thrombus was shortest at 7days following thrombus induction and returned to that of blood as the thrombus resolved. T1 relaxation time was related to thrombus methemoglobin formation and further processing. Studies in inducible nitric oxide synthase (iNOS−/−)–deficient mice revealed that inducible nitric oxide synthase mediates oxidation of erythrocyte lysis–derived iron to paramagnetic Fe3+, which causes thrombus T1 relaxation time shortening. Studies using chemokine receptor-2–deficient mice (Ccr2−/−) revealed that the return of the T1 signal to that of blood is regulated by removal of Fe3+ by macrophages that accumulate in the thrombus during its resolution. Quantification of T1 relaxation time was a good predictor of successful thrombolysis with a cutoff point of <747 ms having a sensitivity and specificity to predict successful lysis of 83% and 94%, respectively. Conclusions The source of the T1 signal in the thrombus results from the oxidation of iron (released from the lysis of trapped erythrocytes in the thrombus) to its paramagnetic Fe3+ form. Quantification of T1 relaxation time appears to be a good predictor of the success of thrombolysis. PMID:23820077

  17. Vibration acceleration promotes bone formation in rodent models

    PubMed Central

    Uchida, Ryohei; Nakata, Ken; Kawano, Fuminori; Yonetani, Yasukazu; Ogasawara, Issei; Nakai, Naoya; Mae, Tatsuo; Matsuo, Tomohiko; Tachibana, Yuta; Yokoi, Hiroyuki; Yoshikawa, Hideki

    2017-01-01

    All living tissues and cells on Earth are subject to gravitational acceleration, but no reports have verified whether acceleration mode influences bone formation and healing. Therefore, this study was to compare the effects of two acceleration modes, vibration and constant (centrifugal) accelerations, on bone formation and healing in the trunk using BMP 2-induced ectopic bone formation (EBF) mouse model and a rib fracture healing (RFH) rat model. Additionally, we tried to verify the difference in mechanism of effect on bone formation by accelerations between these two models. Three groups (low- and high-magnitude vibration and control-VA groups) were evaluated in the vibration acceleration study, and two groups (centrifuge acceleration and control-CA groups) were used in the constant acceleration study. In each model, the intervention was applied for ten minutes per day from three days after surgery for eleven days (EBF model) or nine days (RFH model). All animals were sacrificed the day after the intervention ended. In the EBF model, ectopic bone was evaluated by macroscopic and histological observations, wet weight, radiography and microfocus computed tomography (micro-CT). In the RFH model, whole fracture-repaired ribs were excised with removal of soft tissue, and evaluated radiologically and histologically. Ectopic bones in the low-magnitude group (EBF model) had significantly greater wet weight and were significantly larger (macroscopically and radiographically) than those in the other two groups, whereas the size and wet weight of ectopic bones in the centrifuge acceleration group showed no significant difference compared those in control-CA group. All ectopic bones showed calcified trabeculae and maturated bone marrow. Micro-CT showed that bone volume (BV) in the low-magnitude group of EBF model was significantly higher than those in the other two groups (3.1±1.2mm3 v.s. 1.8±1.2mm3 in high-magnitude group and 1.3±0.9mm3 in control-VA group), but BV in the

  18. Vibration acceleration promotes bone formation in rodent models.

    PubMed

    Uchida, Ryohei; Nakata, Ken; Kawano, Fuminori; Yonetani, Yasukazu; Ogasawara, Issei; Nakai, Naoya; Mae, Tatsuo; Matsuo, Tomohiko; Tachibana, Yuta; Yokoi, Hiroyuki; Yoshikawa, Hideki

    2017-01-01

    All living tissues and cells on Earth are subject to gravitational acceleration, but no reports have verified whether acceleration mode influences bone formation and healing. Therefore, this study was to compare the effects of two acceleration modes, vibration and constant (centrifugal) accelerations, on bone formation and healing in the trunk using BMP 2-induced ectopic bone formation (EBF) mouse model and a rib fracture healing (RFH) rat model. Additionally, we tried to verify the difference in mechanism of effect on bone formation by accelerations between these two models. Three groups (low- and high-magnitude vibration and control-VA groups) were evaluated in the vibration acceleration study, and two groups (centrifuge acceleration and control-CA groups) were used in the constant acceleration study. In each model, the intervention was applied for ten minutes per day from three days after surgery for eleven days (EBF model) or nine days (RFH model). All animals were sacrificed the day after the intervention ended. In the EBF model, ectopic bone was evaluated by macroscopic and histological observations, wet weight, radiography and microfocus computed tomography (micro-CT). In the RFH model, whole fracture-repaired ribs were excised with removal of soft tissue, and evaluated radiologically and histologically. Ectopic bones in the low-magnitude group (EBF model) had significantly greater wet weight and were significantly larger (macroscopically and radiographically) than those in the other two groups, whereas the size and wet weight of ectopic bones in the centrifuge acceleration group showed no significant difference compared those in control-CA group. All ectopic bones showed calcified trabeculae and maturated bone marrow. Micro-CT showed that bone volume (BV) in the low-magnitude group of EBF model was significantly higher than those in the other two groups (3.1±1.2mm3 v.s. 1.8±1.2mm3 in high-magnitude group and 1.3±0.9mm3 in control-VA group), but BV in the

  19. Right ventricular outflow tract aneurysm with thrombus

    PubMed Central

    Peer, Syed Murfad; Bhat, P.S. Seetharama; Furtado, Arul Dominic; Chikkatur, Raghavendra

    2012-01-01

    Right ventricular outflow tract (RVOT) aneurysm is a known complication of tetralogy of Fallot repair when a ventriculotomy is done. It leads to RV dysfunction and may require re-operation. We describe a rare instance of a patient who developed an RVOT aneurysm after trans-ventricular repair of tetralogy of Fallot, which was complicated with the formation of a thrombus in the aneurysm sac. The patient underwent re-operation with thrombectomy, excision of the RVOT aneurysm and pulmonary valve replacement. To the best of our knowledge, the occurrence of this combination and its implications have not been reported. PMID:22232231

  20. Oral Thrombus: Report of 122 cases with clinically descriptive data.

    PubMed

    Tobouti, P-L; Pigatti, F-M; Martins-Mussi, M-C; Machado de Sousa, S-C-O

    2017-05-01

    The aim of the present study was to assess the frequency and characterize clinic-pathologic aspects of thrombus occurring as a single lesion or in association with other oral pathologies. 122 cases of thrombus from the oral cavity were retrieved. Information regarding site of the lesion, age, sex and clinical diagnosis or hypothesis and associated lesions were collected from the patients' records. The lesions occurred in a wide age range but the 5th decade was the most prevalent and female patients were more affected. The most frequent site for the lesion was the lip, followed by tongue, buccal mucosa, alveolar ridge, gingiva, floor of the mouth and vestibule. Thirty-five cases were associated with other vascular anomalies or actinic cheilitis. Microscopically, typical thrombus morphology was present. Organized thrombus presented neovascularization and fibroblasts, associated with hemorrhagic areas. Only 4 cases of oral thrombus have been described in the oral cavity. Given the limited number of cases reported, the importance of a thrombus in the oral cavity is not well established. This study contributes to establishing the profile of patients presenting oral thrombus, a lesion not rare but not well documented.

  1. Extracellular cyclophilin A activates platelets via EMMPRIN (CD147) and PI3K/Akt signaling, which promotes platelet adhesion and thrombus formation in vitro and in vivo.

    PubMed

    Seizer, Peter; Ungern-Sternberg, Saskia N I V; Schönberger, Tanja; Borst, Oliver; Münzer, Patrick; Schmidt, Eva-Maria; Mack, Andreas F; Heinzmann, David; Chatterjee, Madhumita; Langer, Harald; Malešević, Miroslav; Lang, Florian; Gawaz, Meinrad; Fischer, Gunter; May, Andreas E

    2015-03-01

    Cyclophilin A (CyPA) is secreted under inflammatory conditions by various cell types. Whereas the important role of intracellular CyPA for platelet function has been reported, the effect of extracellular CyPA on platelet function has not been investigated yet. Inhibition of extracellular CyPA through a novel specific inhibitor MM284 reduced thrombus after ferric chloride-induced injury in vivo. In vitro extracellular CyPA enhanced thrombus formation even in CyPA(-/-) platelets. Treatment of isolated platelets with recombinant CyPA resulted in platelet degranulation in a time- and dose-dependent manner. Inhibition of the platelet surface receptor extracellular matrix metalloproteinase inducer (cluster of differentiation 147) by an anticluster of differentiation 147 monoclonal antibody significantly reduced CyPA-dependent platelet degranulation. Pretreatment of platelets with CyPA enhanced their recruitment to mouse carotid arteries after arterial injury, which could be inhibited by an anticluster of differentiation 147 monoclonal antibody (intravital microscopy). The role of extracellular CyPA in adhesion could be confirmed by infusing CyPA(-/-) platelets in CyPA(+/+) mice and by infusing CyPA(+/+) platelets in CyPA(-/-) mice. Stimulation of platelets with CyPA induced phosphorylation of Akt, which could in turn be inhibited in the presence of phosphoinositid-3-kinase inhibitors. Akt-1(-/-) platelets revealed a markedly decreased degranulation on CyPA stimulation. Finally, ADP-induced platelet aggregation was attenuated by MM284, as well as by inhibiting paracrine-secreted CyPA without directly affecting Ca(2+)-signaling. Extracellular CyPA activates platelets via cluster of differentiation 147-mediated phosphoinositid-3-kinase/Akt-signaling, leading to enhanced adhesion and thrombus formation independently of intracellular CyPA. Targeting extracellular CyPA via a specific inhibitor may be a promising strategy for platelet inhibition without affecting critical

  2. Development of a real-time and quantitative thrombus sensor for an extracorporeal centrifugal blood pump by near-infrared light

    PubMed Central

    Sakota, Daisuke; Fujiwara, Tatsuki; Ohuchi, Katsuhiro; Kuwana, Katsuyuki; Yamazaki, Hiroyuki; Kosaka, Ryo; Nishida, Masahiro; Mizuno, Tomohiro; Arai, Hirokuni; Maruyama, Osamu

    2017-01-01

    We developed an optical thrombus sensor for a monopivot extracorporeal centrifugal blood pump. In this study, we investigated its quantitative performance for thrombus detection in acute animal experiments of left ventricular assist using the pump on pathogen-free pigs. Optical fibers were set in the driver unit of the pump. The incident light at the near-infrared wavelength of 810 nm was aimed at the pivot bearing, and the resulting scattered light was guided to the optical fibers. The detected signal was analyzed to obtain the thrombus formation level. As a result, real-time and quantitative monitoring of the thrombus surface area on the pivot bearing was achieved with an accuracy of 3.6 ± 2.3 mm2. In addition, the sensing method using the near-infrared light was not influenced by changes in the oxygen saturation and the hematocrit. It is expected that the developed sensor will be useful for optimal anticoagulation management for long-term extracorporeal circulation therapies. PMID:29359096

  3. Development of a real-time and quantitative thrombus sensor for an extracorporeal centrifugal blood pump by near-infrared light.

    PubMed

    Sakota, Daisuke; Fujiwara, Tatsuki; Ohuchi, Katsuhiro; Kuwana, Katsuyuki; Yamazaki, Hiroyuki; Kosaka, Ryo; Nishida, Masahiro; Mizuno, Tomohiro; Arai, Hirokuni; Maruyama, Osamu

    2018-01-01

    We developed an optical thrombus sensor for a monopivot extracorporeal centrifugal blood pump. In this study, we investigated its quantitative performance for thrombus detection in acute animal experiments of left ventricular assist using the pump on pathogen-free pigs. Optical fibers were set in the driver unit of the pump. The incident light at the near-infrared wavelength of 810 nm was aimed at the pivot bearing, and the resulting scattered light was guided to the optical fibers. The detected signal was analyzed to obtain the thrombus formation level. As a result, real-time and quantitative monitoring of the thrombus surface area on the pivot bearing was achieved with an accuracy of 3.6 ± 2.3 mm 2 . In addition, the sensing method using the near-infrared light was not influenced by changes in the oxygen saturation and the hematocrit. It is expected that the developed sensor will be useful for optimal anticoagulation management for long-term extracorporeal circulation therapies.

  4. Sixty-Four-Section Cardiac Computed Tomography in Mechanical Prosthetic Heart Valve Dysfunction: Thrombus or Pannus.

    PubMed

    Gündüz, Sabahattin; Özkan, Mehmet; Kalçik, Macit; Gürsoy, Ozan Mustafa; Astarcioğlu, Mehmet Ali; Karakoyun, Süleyman; Aykan, Ahmet Çağri; Biteker, Murat; Gökdeniz, Tayyar; Kaya, Hasan; Yesin, Mahmut; Duran, Nilüfer Ekşi; Sevinç, Deniz; Güneysu, Tahsin

    2015-12-01

    Distinguishing pannus and thrombus in patients with prosthetic valve dysfunction is essential for the selection of proper treatment. We have investigated the utility of 64-slice multidetector computed tomography (MDCT) in distinguishing between pannus and thrombus, the latter amenable to thrombolysis. Sixty-two (23 men, mean age 44±14 years) patients with suspected mechanical prosthetic valve dysfunction assessed by transesophageal echocardiography were included in this prospective observational trial. Subsequently, MDCT was performed before any treatment was started. Periprosthetic masses were detected by MDCT in 46 patients, and their attenuation values were measured as Hounsfield Units (HU). Patients underwent thrombolysis unless contraindicated, and those with a contraindication or failed thrombolysis underwent surgery. A mass which was completely lysed or surgically detected as a clot was classified as thrombus, whereas a mass which was surgically detected as tissue overgrowth was classified as pannus. A definitive diagnosis could be achieved in 37 patients with 39 MDCT masses (22 thrombus and 17 pannus). The mean attenuation value of 22 thrombotic masses was significantly lower than that in 17 pannus (87±59 versus 322±122; P<0.001). Area under the receiver operating characteristic curve was 0.96 (95% confidence interval: 0.91-0.99; P<0.001), and a cutoff point of HU≥145 provided high sensitivity (87.5%) and specificity (95.5%) in discriminating pannus from thrombus. Complete lysis was more common for masses with HU<90 compared with those with HU 90 to 145 (100% versus 42.1%; P=0.007). Sixty-four slice MDCT is helpful in identifying masses amenable to thrombolysis in patients with prosthetic valve dysfunction. A high (HU≥145) attenuation suggests pannus overgrowth, whereas a lower value is associated with thrombus formation. A higher attenuation (HU>90) is associated with reduced lysis rates. © 2015 American Heart Association, Inc.

  5. A Microstructurally Inspired Damage Model for Early Venous Thrombus

    PubMed Central

    Rausch, Manuel K.; Humphrey, Jay D.

    2015-01-01

    Accumulative damage may be an important contributor to many cases of thrombotic disease progression. Thus, a complete understanding of the pathological role of thrombus requires an understanding of its mechanics and in particular mechanical consequences of damage. In the current study, we introduce a novel microstructurally inspired constitutive model for thrombus that considers a non-uniform distribution of microstructural fibers at various crimp levels and employs one of the distribution parameters to incorporate stretch-driven damage on the microscopic level. To demonstrate its ability to represent the mechanical behavior of thrombus, including a recently reported Mullins type damage phenomenon, we fit our model to uniaxial tensile test data of early venous thrombus. Our model shows an agreement with these data comparable to previous models for damage in elastomers with the added advantages of a microstructural basis and fewer model parameters. We submit that our novel approach marks another important step toward modeling the evolving mechanics of intraluminal thrombus, specifically its damage, and hope it will aid in the study of physiological and pathological thrombotic events. PMID:26523784

  6. Treatment of hepatocellular carcinoma with portal vein tumor thrombus: advances and challenges.

    PubMed

    Jiang, Jin-Fang; Lao, Yong-Cong; Yuan, Bao-Hong; Yin, Jun; Liu, Xin; Chen, Long; Zhong, Jian-Hong

    2017-05-16

    Portal vein tumor thrombus is a frequent, challenging complication in hepatocellular carcinoma. Hepatocellular carcinoma patients with portal vein tumor thrombus may show worse liver function, less treatment tolerance and worse prognosis than patients without portal vein tumor thrombus, and they may be at higher risk of comorbidity related to portal hypertension. Western and some Asian guidelines stratify hepatocellular carcinoma with portal vein tumor thrombus together with metastatic hepatocellular carcinoma and therefore recommend only palliative treatment with sorafenib or other systemic agents. In recent years, more treatment options have become available for hepatocellular carcinoma patients with portal vein tumor thrombus, and an evidence-based approach to optimizing disease management and treatment has become more widespread. Nevertheless, consensus policies for managing hepatocellular carcinoma with portal vein tumor thrombus have not been established. This comprehensive literature review, drawing primarily on studies published after 2010, examines currently available management options for patients with hepatocellular carcinoma and portal vein tumor thrombus.

  7. The role of Nox1 and Nox2 in GPVI-dependent platelet activation and thrombus formation☆

    PubMed Central

    Walsh, T.G.; Berndt, M.C.; Carrim, N.; Cowman, J.; Kenny, D.; Metharom, P.

    2014-01-01

    Background Activation of the platelet-specific collagen receptor, glycoprotein (GP) VI, induces intracellular reactive oxygen species (ROS) production; however the relevance of ROS to GPVI-mediated platelet responses remains unclear. Objective The objective of this study was to explore the role of the ROS-producing NADPH oxidase (Nox)1 and 2 complexes in GPVI-dependent platelet activation and collagen-induced thrombus formation. Methods and results ROS production was measured by quantitating changes in the oxidation-sensitive dye, H2DCF-DA, following platelet activation with the GPVI-specific agonist, collagen related peptide (CRP). Using a pharmacological inhibitor specific for Nox1, 2-acetylphenothiazine (ML171), and Nox2 deficient mice, we show that Nox1 is the key Nox homolog regulating GPVI-dependent ROS production. Nox1, but not Nox2, was essential for CRP-dependent thromboxane (Tx)A2 production, which was mediated in part through p38 MAPK signaling; while neither Nox1 nor Nox2 was significantly involved in regulating CRP-induced platelet aggregation/integrin αIIbβ3 activation, platelet spreading, or dense granule and α-granule release (ATP release and P-selectin surface expression, respectively). Ex-vivo perfusion analysis of mouse whole blood revealed that both Nox1 and Nox2 were involved in collagen-mediated thrombus formation at arterial shear. Conclusion Together these results demonstrate a novel role for Nox1 in regulating GPVI-induced ROS production, which is essential for optimal p38 activation and subsequent TxA2 production, providing an explanation for reduced thrombus formation following Nox1 inhibition. PMID:24494191

  8. Thrombus segmentation by texture dynamics from microscopic image sequences

    NASA Astrophysics Data System (ADS)

    Brieu, Nicolas; Serbanovic-Canic, Jovana; Cvejic, Ana; Stemple, Derek; Ouwehand, Willem; Navab, Nassir; Groher, Martin

    2010-03-01

    The genetic factors of thrombosis are commonly explored by microscopically imaging the coagulation of blood cells induced by injuring a vessel of mice or of zebrafish mutants. The latter species is particularly interesting since skin transparency permits to non-invasively acquire microscopic images of the scene with a CCD camera and to estimate the parameters characterizing the thrombus development. These parameters are currently determined by manual outlining, which is both error prone and extremely time consuming. Even though a technique for automatic thrombus extraction would be highly valuable for gene analysts, little work can be found, which is mainly due to very low image contrast and spurious structures. In this work, we propose to semi-automatically segment the thrombus over time from microscopic image sequences of wild-type zebrafish larvae. To compensate the lack of valuable spatial information, our main idea consists of exploiting the temporal information by modeling the variations of the pixel intensities over successive temporal windows with a linear Markov-based dynamic texture formalization. We then derive an image from the estimated model parameters, which represents the probability of a pixel to belong to the thrombus. We employ this probability image to accurately estimate the thrombus position via an active contour segmentation incorporating also prior and spatial information of the underlying intensity images. The performance of our approach is tested on three microscopic image sequences. We show that the thrombus is accurately tracked over time in each sequence if the respective parameters controlling prior influence and contour stiffness are correctly chosen.

  9. Evaluation of the thrombus of abdominal aortic aneurysms using contrast enhanced ultrasound - preliminary results

    NASA Astrophysics Data System (ADS)

    Łukasiewicz, Adam; Garkowski, Adam; Rutka, Katarzyna; Janica, Jacek; Łebkowska, Urszula

    2016-09-01

    It is hypothesized that the degree of vascularization of the thrombus may have a significant impact on the rupture of aortic aneurysms. The presence of neovascularization of the vessel wall and mural thrombus has been confirmed only in histopathological studies. However, no non-invasive imaging technique of qualitative assessment of thrombus and neovascularization has been implemented so far. Contrast-enhanced ultrasound (CEUS) has been proposed as a feasible and minimally invasive technique for in vivo visualization of neovascularization in the evaluation of tumors and atherosclerotic plaques. The aim of this study was the evaluation of mural thrombus and AAAs wall with CEUS. CEUS was performed in a group of seventeen patients with AAAs. The mural thrombus enhancement was recognized in 12 cases, yet no significant correlation between the degree of contrast enhancement and AAAs diameter, thrombus width, and thrombus echogenicity was found. We observed a rise in AAAs thrombus heterogeneity with the increase in the aneurysm diameter (r = 0.62, p = 0.017). In conclusion CEUS can visualize small channels within AAAs thrombus, which could be a result of an ongoing angiogenesis. There is a need for further research to find out whether the degree of vascularization of the thrombus may have a significant impact on the rupture of aneurysms.

  10. A Left Main Coronary Artery Thrombus Presenting as a Non St Elevation MI.

    PubMed

    Ezema, U; Daberkow, D; Delord, T; Guidry, L; Sells, N R

    2017-01-01

    Left main coronary artery (LMCA); thrombus with an acute myocardial infarction identified with coronary angiography is a clinically rare condition with an extremely high mortality rate. We present a case of LMCA thrombus that presented as a non-ST elevation myocardial infarction (NSTEMI);. A 45-year-old woman with a history of tobacco use and hyperlipidemia presented with a complaint of 10/10 "hard pain" across her chest radiating to her left shoulder and breast which woke her from sleep. The pain was constant and severe, with no alleviation with rest. She had not experienced anything like this before. Workup revealed an upward trending troponin (1.98.989.79);, and an EKG with some tachycardia but no ST elevation or T wave changes. Her CBC, CMP and coagulation studies were unremarkable. A toxicology screen was positive for opiates and benzodiazepines, medications she was on for pain and anxiety respectively. ACS protocol was started with DAPT, LMWH, Statin, ACEi, and Beta-blocker. An angiogram revealed a large thrombus in the LM coronary artery extending into the aorta with concomitant 99 percent stenosis of distal LAD. 2D Echo w/ bubble contrast was significant for PFO, akinetic apical inferior and anterior wall. The mid antero-septum and apical lateral wall were hypokinetic. Interventional Cardiology and CTS recommended conservative management with medical optimization (Continue DAPT, heparin);, watchful waiting for the thrombus to resorb. Left main coronary artery thrombosis (LMCAT); identified during coronary angiography is a rare and challenging condition. It is a life threatening condition with an approximate incidence rate of 0.8 percent . It is thought to be secondary to plaque rupture with subsequent thrombus formation that is associated with persistent hypercoagulable state, cocaine induced plaque rupture or coronary vasospasm, post-partum state and embolization of intra-cardiac masses. The patient presentation can vary from sudden cardiac death to

  11. Matrix Metalloproteinase 9 (MMP-9) Regulates Vein Wall Biomechanics in Murine Thrombus Resolution

    PubMed Central

    Nguyen, Khanh P.; McGilvray, Kirk C.; Puttlitz, Christian M.; Mukhopadhyay, Subhradip; Chabasse, Christine; Sarkar, Rajabrata

    2015-01-01

    Objective Deep venous thrombosis is a common vascular problem with long-term complications including post-thrombotic syndrome. Post-thrombotic syndrome consists of leg pain, swelling and ulceration that is related to incomplete or maladaptive resolution of the venous thrombus as well as loss of compliance of the vein wall. We examine the role of metalloproteinase-9 (MMP-9), a gene important in extracellular remodeling in other vascular diseases, in mediating thrombus resolution and biomechanical changes of the vein wall. Methods and Results The effects of targeted deletion of MMP-9 were studied in an in vivo murine model of thrombus resolution using the FVB strain of mice. MMP-9 expression and activity significantly increased on day 3 after DVT. The lack of MMP-9 impaired thrombus resolution by 27% and this phenotype was rescued by the transplantation of wildtype bone marrow cells. Using novel biomechanical techniques, we demonstrated that the lack of MMP-9 significantly decreased thrombus-induced loss of vein wall compliance. Biomechanical analysis of the contribution of individual structural components showed that MMP-9 affected the elasticity of the extracellular matrix and collagen-elastin fibers. Biochemical and histological analyses correlated with these biomechanical effects as thrombi of mice lacking MMP-9 had significantly fewer macrophages and collagen as compared to those of wildtype mice. Conclusions MMP-9 mediates thrombus-induced loss of vein wall compliance by increasing stiffness of the extracellular matrix and collagen-elastin fibers during thrombus resolution. MMP-9 also mediates macrophage and collagen content of the resolving thrombus and bone-marrow derived MMP-9 plays a role in resolution of thrombus mass. These disparate effects of MMP-9 on various aspects of thrombus illustrate the complexity of individual protease function on biomechanical and morphometric aspects of thrombus resolution. PMID:26406902

  12. Quantification of thrombus formation in malapposed coronary stents deployed in vitro through imaging analysis.

    PubMed

    Brown, Jonathan; O'Brien, Caroline C; Lopes, Augusto C; Kolandaivelu, Kumaran; Edelman, Elazer R

    2018-04-11

    Stent thrombosis is a major complication of coronary stent and scaffold intervention. While often unanticipated and lethal, its incidence is low making mechanistic examination difficult through clinical investigation alone. Thus, throughout the technological advancement of these devices, experimental models have been indispensable in furthering our understanding of device safety and efficacy. As we refine model systems to gain deeper insight into adverse events, it is equally important that we continue to refine our measurement methods. We used digital signal processing in an established flow loop model to investigate local flow effects due to geometric stent features and ultimately its relationship to thrombus formation. A new metric of clot distribution on each microCT slice termed normalized clot ratio was defined to quantify this distribution. Three under expanded coronary bare-metal stents were run in a flow loop model to induce clotting. Samples were then scanned in a MicroCT machine and digital signal processing methods applied to analyze geometric stent conformation and spatial clot formation. Results indicated that geometric stent features play a significant role in clotting patterns, specifically at a frequency of 0.6225 Hz corresponding to a geometric distance of 1.606 mm. The magnitude-squared coherence between geometric features and clot distribution was greater than 0.4 in all samples. In stents with poor wall apposition, ranging from 0.27 mm to 0.64 mm maximum malapposition (model of real-world heterogeneity), clots were found to have formed in between stent struts rather than directly adjacent to struts. This early work shows how the combination of tools in the areas of image processing and signal analysis can advance the resolution at which we are able to define thrombotic mechanisms in in vitro models, and ultimately, gain further insight into clinical performance. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Associations Between Collateral Status and Thrombus Characteristics and Their Impact in Anterior Circulation Stroke.

    PubMed

    Alves, Heitor C; Treurniet, Kilian M; Dutra, Bruna G; Jansen, Ivo G H; Boers, Anna M M; Santos, Emilie M M; Berkhemer, Olvert A; Dippel, Diederik W J; van der Lugt, Aad; van Zwam, Wim H; van Oostenbrugge, Robert J; Lingsma, Hester F; Roos, Yvo B W E M; Yoo, Albert J; Marquering, Henk A; Majoie, Charles B L M

    2018-02-01

    Thrombus characteristics and collateral score are associated with functional outcome in patients with acute ischemic stroke. It has been suggested that they affect each other. The aim of this study is to evaluate the association between clot burden score, thrombus perviousness, and collateral score and to determine whether collateral score influences the association of thrombus characteristics with functional outcome. Patients with baseline thin-slice noncontrast computed tomography and computed tomographic angiography images from the MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands) were included (n=195). Collateral score and clot burden scores were determined on baseline computed tomographic angiography. Thrombus attenuation increase was determined by comparing thrombus density on noncontrast computed tomography and computed tomographic angiography using a semiautomated method. The association of collateral score with clot burden score and thrombus attenuation increase was evaluated with linear regression. Mediation and effect modification analyses were used to assess the influence of collateral score on the association of clot burden score and thrombus attenuation increase with functional outcome. A higher clot burden score (B=0.063; 95% confidence interval, 0.008-0.118) and a higher thrombus attenuation increase (B=0.014; 95% confidence interval, 0.003-0.026) were associated with higher collateral score. Collateral score mediated the association of clot burden score with functional outcome. The association between thrombus attenuation increase and functional outcome was modified by the collateral score, and this association was stronger in patients with moderate and good collaterals. Patients with lower thrombus burden and higher thrombus perviousness scores had higher collateral score. The positive effect of thrombus perviousness on clinical outcome was only present in patients with

  14. Clinical management of renal cell carcinoma with venous tumor thrombus.

    PubMed

    Agochukwu, Nnenaya; Shuch, Brian

    2014-06-01

    Venous invasion is common in advanced renal cell carcinoma (RCC) due to the unique biology of this cancer. The presence of a tumor thrombus often makes clinical management challenging. In this review, we detail specific preoperative, perioperative, and surgical strategies involving the care of the complex kidney cancer patient with venous tumor involvement. We performed a comprehensive review of selected peer-reviewed publications regarding RCC tumor thrombus biology, medical and surgical management techniques, and immediate and long-term outcomes. The perioperative management may require special imaging techniques, preoperative testing, very recent imaging, and consultation with other surgical services. There are various approaches to these patients as the clinical presentation, stage of disease, primary tumor size, level of thrombus, degree of venous occlusion, presence of bland thrombus, and primary tumor laterality influence management. Select patients with metastatic disease can do well with cytoreductive nephrectomy and thrombectomy. Those with localized disease have a high risk of recurrence; however, some patients can exhibit durable survival with surgery alone. The evolving surgical and medical treatments are discussed. Even when these surgeries are performed in high volume centers, significant perioperative complications are common and greater complications are seen with higher thrombus extent. If surgery is attempted, it is important for urologic oncologists to follow strict attention to specific surgical principles. These general principles include complete vascular control, avoidance of thrombus embolization, close hemodynamic monitoring, and institutional resources for caval resection/replacement and venous bypass if necessary.

  15. Retrievable Vena Cava Filters in Major Trauma Patients: Prevalence of Thrombus Within the Filter

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mahrer, Arie; Zippel, Douglas; Garniek, Alexander

    The purpose of this study was to report the prevalence of thrombus within a retrievable vena cava filter inserted prophylactically in major trauma patients referred for filter extraction. Between November 2002 and August 2005, 80 retrievable inferior vena cava filters (68 Optease and 12 Gunther-Tulip) were inserted into critically injured trauma patients (mean injury severity score 33.5). The filters were inserted within 1 to 6 (mean 2) days of injury. Thirty-seven patients were referred for filter removal (32 with Optease and 5 with Gunther-Tulip). The indwelling time was 7 to 22 (mean 13) days. All patients underwent inferior vena cavographymore » prior to filter removal. There were no insertion-related complications and all filters were successfully deployed. Forty-three (54%) of the 80 patients were not referred for filter removal, as these patients continued to have contraindications to anticoagulation. Thirty-seven patients (46%) were referred for filter removal. In eight of them (22%) a large thrombus was seen within the filters and they were left in place, all with the Optease device. The other 29 filters (36%) were removed uneventfully.We conclude that the relatively high prevalence of intrafilter thrombi with the Optease filter may be explained by either spontaneous thrombus formation or captured emboli.« less

  16. Retention of Information Taught in Introductory Psychology Courses across Different Accelerated Course Formats

    ERIC Educational Resources Information Center

    Deichert, Nathan T.; Maxwell, Shannon J.; Klotz, Joseph

    2016-01-01

    The current study is a quasi-experimental examination of the effects of traditional and accelerated course formats on learning retention. The study analyzed data on an end-of-course exam collected from 132 students enrolled in introductory psychology courses across 3 course formats: a traditional 16-week format, a 5-week accelerated format, and an…

  17. Statins improve the resolution of established murine venous thrombosis: reductions in thrombus burden and vein wall scarring.

    PubMed

    Kessinger, Chase W; Kim, Jin Won; Henke, Peter K; Thompson, Brian; McCarthy, Jason R; Hara, Tetsuya; Sillesen, Martin; Margey, Ronan J P; Libby, Peter; Weissleder, Ralph; Lin, Charles P; Jaffer, Farouc A

    2015-01-01

    Despite anticoagulation therapy, up to one-half of patients with deep vein thrombosis (DVT) will develop the post-thrombotic syndrome (PTS). Improving the long-term outcome of DVT patients at risk for PTS will therefore require new approaches. Here we investigate the effects of statins--lipid-lowering agents with anti-thrombotic and anti-inflammatory properties--in decreasing thrombus burden and decreasing vein wall injury, mediators of PTS, in established murine stasis and non-stasis chemical-induced venous thrombosis (N = 282 mice). Treatment of mice with daily atorvastatin or rosuvastatin significantly reduced stasis venous thrombus burden by 25% without affecting lipid levels, blood coagulation parameters, or blood cell counts. Statin-driven reductions in VT burden (thrombus mass for stasis thrombi, intravital microscopy thrombus area for non-stasis thrombi) compared similarly to the therapeutic anticoagulant effects of low molecular weight heparin. Blood from statin-treated mice showed significant reductions in platelet aggregation and clot stability. Statins additionally reduced thrombus plasminogen activator inhibitor-1 (PAI-1), tissue factor, neutrophils, myeloperoxidase, neutrophil extracellular traps (NETs), and macrophages, and these effects were most notable in the earlier timepoints after DVT formation. In addition, statins reduced DVT-induced vein wall scarring by 50% durably up to day 21 in stasis VT, as shown by polarized light microscopy of picrosirius red-stained vein wall collagen. The overall results demonstrate that statins improve VT resolution via profibrinolytic, anticoagulant, antiplatelet, and anti-vein wall scarring effects. Statins may therefore offer a new pharmacotherapeutic approach to improve DVT resolution and to reduce the post-thrombotic syndrome, particularly in subjects who are ineligible for anticoagulation therapy.

  18. Statins Improve the Resolution of Established Murine Venous Thrombosis: Reductions in Thrombus Burden and Vein Wall Scarring

    PubMed Central

    Kessinger, Chase W.; Kim, Jin Won; Henke, Peter K.; Thompson, Brian; McCarthy, Jason R.; Hara, Tetsuya; Sillesen, Martin; Margey, Ronan J. P.; Libby, Peter; Weissleder, Ralph; Lin, Charles P.; Jaffer, Farouc A.

    2015-01-01

    Despite anticoagulation therapy, up to one-half of patients with deep vein thrombosis (DVT) will develop the post-thrombotic syndrome (PTS). Improving the long-term outcome of DVT patients at risk for PTS will therefore require new approaches. Here we investigate the effects of statins—lipid-lowering agents with anti-thrombotic and anti-inflammatory properties—in decreasing thrombus burden and decreasing vein wall injury, mediators of PTS, in established murine stasis and non-stasis chemical-induced venous thrombosis (N = 282 mice). Treatment of mice with daily atorvastatin or rosuvastatin significantly reduced stasis venous thrombus burden by 25% without affecting lipid levels, blood coagulation parameters, or blood cell counts. Statin-driven reductions in VT burden (thrombus mass for stasis thrombi, intravital microscopy thrombus area for non-stasis thrombi) compared similarly to the therapeutic anticoagulant effects of low molecular weight heparin. Blood from statin-treated mice showed significant reductions in platelet aggregation and clot stability. Statins additionally reduced thrombus plasminogen activator inhibitor-1 (PAI-1), tissue factor, neutrophils, myeloperoxidase, neutrophil extracellular traps (NETs), and macrophages, and these effects were most notable in the earlier timepoints after DVT formation. In addition, statins reduced DVT-induced vein wall scarring by 50% durably up to day 21 in stasis VT, as shown by polarized light microscopy of picrosirius red-stained vein wall collagen. The overall results demonstrate that statins improve VT resolution via profibrinolytic, anticoagulant, antiplatelet, and anti-vein wall scarring effects. Statins may therefore offer a new pharmacotherapeutic approach to improve DVT resolution and to reduce the post-thrombotic syndrome, particularly in subjects who are ineligible for anticoagulation therapy. PMID:25680183

  19. Huge Free-Floating Thrombus in the Internal Carotid Artery.

    PubMed

    Tanriverdi, Uygur; Kizilkilic, Osman; Ince, Birsen

    2017-12-01

    Free-floating thrombus in the carotid artery is extremely rare. A 70-year-old male patient with pre-existing Crohn's disease admitted to our clinic with recurrent transient ischemic attacks. Angiography showed a huge thrombus in internal carotid artery. He responded to anticoagulation treatment and delayed endovascular intervention. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  20. Rivaroxaban attenuates thrombosis by targeting the NF-κB signaling pathway in a rat model of deep venous thrombus

    PubMed Central

    Ma, Junhao; Li, Xinxi; Wang, Yang; Yang, Zhenwei; Luo, Jun

    2017-01-01

    Anticoagulant therapy is commonly used for the prevention and treatment of patients with deep venous thrombus. Evidence has shown that rivaroxaban is a potential oral anticoagulant drug for the acute treatment of venous thromboembolism. However, the rivaroxaban-mediated molecular mechanism involved in the progression of deep venous thrombosis has not been investigated. In the present study, we investigated the efficacy of rivaroxaban and the underlying signaling pathways in the prevention and treatment of rats with deep venous thrombosis. A rat model with deep vein thrombus formation was established and received treatment with rivaroxaban or PBS as control. The thrombin-activatable fibrinolysis inhibitor (TAFI) and plasminogen activator inhibitor-1 (PAI-1) were analyzed both in vitro and in vivo. The progression of thrombosis and stroke was evaluated after treatment with rivaroxaban or PBS. Nuclear factor-κB (NF-κB) signaling pathway in venous endothelial cells and in the rat model of deep venous thrombus was assessed. The therapeutic effects of rivaroxaban were evaluated as determined by changes in deep venous thrombosis in the rat model. Our results showed that rivaroxaban markedly inhibited TAFI and PAI-1 expression levels, neutrophils, tissue factor, neutrophil extracellular traps (NETs), myeloperoxidase and macrophages in venous endothelial cells and in the rat model of deep venous thrombus. Expression levels of ADP, PAIs, von Willebrand factor (vWF) and thromboxane were downregulated in vein endothelial cells and in serum from the experimental rats. Importantly, the incidences of inferior vena cava filter thrombus were protected by rivaroxaban during heparin-induced thrombolysis deep venous thrombosis in the rat model. We observed that activity of the NF-κB signaling pathway was inhibited by rivaroxaban in vein endothelial cells both in vitro and in vivo. Notably, immunohistology indicated that rivaroxaban attenuated deep venous thrombosis and the

  1. Rivaroxaban attenuates thrombosis by targeting the NF-κB signaling pathway in a rat model of deep venous thrombus.

    PubMed

    Ma, Junhao; Li, Xinxi; Wang, Yang; Yang, Zhenwei; Luo, Jun

    2017-12-01

    Anticoagulant therapy is commonly used for the prevention and treatment of patients with deep venous thrombus. Evidence has shown that rivaroxaban is a potential oral anticoagulant drug for the acute treatment of venous thromboembolism. However, the rivaroxaban-mediated molecular mechanism involved in the progression of deep venous thrombosis has not been investigated. In the present study, we investigated the efficacy of rivaroxaban and the underlying signaling pathways in the prevention and treatment of rats with deep venous thrombosis. A rat model with deep vein thrombus formation was established and received treatment with rivaroxaban or PBS as control. The thrombin-activatable fibrinolysis inhibitor (TAFI) and plasminogen activator inhibitor-1 (PAI-1) were analyzed both in vitro and in vivo. The progression of thrombosis and stroke was evaluated after treatment with rivaroxaban or PBS. Nuclear factor-κB (NF-κB) signaling pathway in venous endothelial cells and in the rat model of deep venous thrombus was assessed. The therapeutic effects of rivaroxaban were evaluated as determined by changes in deep venous thrombosis in the rat model. Our results showed that rivaroxaban markedly inhibited TAFI and PAI-1 expression levels, neutrophils, tissue factor, neutrophil extracellular traps (NETs), myeloperoxidase and macrophages in venous endothelial cells and in the rat model of deep venous thrombus. Expression levels of ADP, PAIs, von Willebrand factor (vWF) and thromboxane were downregulated in vein endothelial cells and in serum from the experimental rats. Importantly, the incidences of inferior vena cava filter thrombus were protected by rivaroxaban during heparin-induced thrombolysis deep venous thrombosis in the rat model. We observed that activity of the NF-κB signaling pathway was inhibited by rivaroxaban in vein endothelial cells both in vitro and in vivo. Notably, immunohistology indicated that rivaroxaban attenuated deep venous thrombosis and the

  2. Early ultrasonographic evaluation of tumor thrombus level during sunitinib therapy for renal cell carcinoma.

    PubMed

    Sano, Futoshi; Fusayasu, Syusei; Otake, Shinji; Yamanaka, Hiroyuki; Tatenuma, Tomoyuki; Sakata, Ryoko; Makiyama, Kazuhide; Nakaigawa, Noboru; Yao, Masahiro; Kubota, Yoshinobu

    2013-10-01

    A 72-year-old man presenting with a 14-cm left renal mass, an inferior vena cava (IVC) tumor thrombus, and pulmonary metastases underwent renal mass biopsy that revealed clear cell renal cell carcinoma. Because of metastases and the extent of the tumor thrombus, sunitinib was administered, which resulted in a marked reduction in the tumor thrombus (from level III to level II after 11 weeks of treatment). Ultrasonography, preceding computed tomography, showed a slight shrinkage of the tumor thrombus level in the first 2 weeks. Therefore, ultrasound may be advantageous to monitor the IVC tumor thrombus level during the early phase of targeted therapy.

  3. Quantification of experimental venous thrombus resolution by longitudinal nanogold-enhanced micro-computed tomography.

    PubMed

    Grover, Steven P; Saha, Prakash; Jenkins, Julia; Mukkavilli, Arun; Lyons, Oliver T; Patel, Ashish S; Sunassee, Kavitha; Modarai, Bijan; Smith, Alberto

    2015-12-01

    The assessment of thrombus size following treatments directed at preventing thrombosis or enhancing its resolution has generally relied on physical or histological methods. This cross-sectional design imposes the need for increased numbers of animals for experiments. Micro-computed tomography (microCT) has been used to detect the presence of venous thrombus in experimental models but has yet to be used in a quantitative manner. In this study, we investigate the use of contrast-enhanced microCT for the longitudinal assessment of experimental venous thrombus resolution. Thrombi induced by stenosis of the inferior vena cava in mice were imaged by contrast-enhanced microCT at 1, 7 and 14 days post-induction (n=18). Thrombus volumes were determined longitudinally by segmentation and 3D volume reconstruction of microCT scans and by standard end-point histological analysis at day 14. An additional group of thrombi were analysed solely by histology at 1, 7 and 14 days post-induction (n=15). IVC resident thrombus was readily detectable by contrast-enhanced microCT. MicroCT-derived measurements of thrombus volume correlated well with time-matched histological analyses (ICC=0.75, P<0.01). Thrombus volumes measured by microCT were significantly greater than those derived from histological analysis (P<0.001). Intra- and inter-observer analyses were highly correlated (ICC=0.99 and 0.91 respectively, P<0.0001). Further histological analysis revealed noticeable levels of contrast agent extravasation into the thrombus that was associated with the presence of neovascular channels, macrophages and intracellular iron deposits. Contrast-enhanced microCT represents a reliable and reproducible method for the longitudinal assessment of venous thrombus resolution providing powerful paired data. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Right Ventricular Thrombus with Behçet's Syndrome

    PubMed Central

    Dogan, Sait M.; Birdane, Alparslan; Korkmaz, Cengiz; Ata, Necmi; Timuralp, Bilgin

    2007-01-01

    Behçet's syndrome is a chronic multisystem disease that presents with recurrent oral and genital ulceration and recurrent uveitis. Cardiac involvement is an extremely rare manifestation of this disorder. A 33-year-old man with Behçet's syndrome was admitted to our department with a history of cough, fever, chest pain, hemoptysis, and weight loss. Transthoracic and transesophageal echocardiography revealed a right ventricular thrombus. After 1 month of treatment with warfarin, cyclophosphamide, and corticosteroid, the intracardiac thrombus resolved. PMID:17948088

  5. Floating arterial thrombus related stroke treated by intravenous thrombolysis.

    PubMed

    Vanacker, P; Cordier, M; Janbieh, J; Federau, C; Michel, P

    2014-01-01

    The effects of intravenous thrombolysis on floating thrombi in cervical and intracranial arteries of acute ischemic stroke patients are unknown. Similarly, the best prevention methods of early recurrences remain controversial. This study aimed to describe the clinical and radiological outcome of thrombolyzed strokes with floating thrombi. We retrospectively analyzed all thrombolyzed stroke patients in our institution between 2003 and 2010 with floating thrombi on acute CT-angiography before the intravenous thrombolysis. The floating thrombus was diagnosed if an elongated thrombus of at least 5 mm length, completely surrounded by contrast on supra-aortic neck or intracerebral arteries, was present on CT-angiography. Demographics, vascular risk factors, and comorbidities were recorded and stroke etiology was determined after a standardized workup. Repeat arterial imaging was performed by CTA at 24 h or before if clinical worsening was noted and then by Doppler and MRA during the first week and at four months. Of 409 thrombolyzed stroke patients undergoing acute CT Angiography, seven (1.7%) had a floating thrombus; of these seven, six had it in the anterior circulation. Demographics, risk factors and stroke severity of these patients were comparable to the other thrombolyzed patients. After intravenous thrombolysis, the floating thrombi resolved completely at 24 h in four of the patients, whereas one had an early recurrent stroke and one developed progressive worsening. One patient developed early occlusion of the carotid artery with floating thrombus and subsequently a TIA. The two patients with a stable floating thrombus had no clinical recurrences. In the literature, only one of four reported cases were found to have a thrombolysis-related early recurrence. Long-term outcome seemed similar in thrombolyzed patients with floating thrombus, despite a possible increase of very early recurrence. It remains to be established whether acute mechanical thrombectomy could be

  6. Early Detection and Quantification of Cerebral Venous Thrombosis by Magnetic Resonance Black Blood Thrombus Imaging (MRBTI)

    PubMed Central

    Yang, Qi; Duan, Jiangang; Fan, Zhaoyang; Qu, Xiaofeng; Xie, Yibin; Nguyen, Christopher; Du, Xiangying; Bi, Xiaoming; Li, Kuncheng; Ji, Xunming; Li, Debiao

    2015-01-01

    Background and Purpose Early diagnosis of cerebral venous and sinus thrombosis (CVT) is currently a major clinical challenge. We proposed a novel MR black-blood thrombus imaging technique(MRBTI) for detection and quantification of CVT. Methods MRBTI was performed on 23 patients with proven CVT and 24 patients with negative CVT confirmed by conventional imaging techniques. Patients were divided into two groups based on the duration of clinical onset: ≤ 7 days (group 1); between 7 and 30 days (group 2). Signal-to-noise ratio (SNR) was calculated for the detected thrombus and contrast-to-noise ratio (CNR) was measured between thrombus and lumen, and also between thrombus and brain tisssue. The feasibility of using MRBTI for thrombus volume measurement was explored and total thrombus volume was calculated for each patient. Results In 23 patients with proven CVT, MRBTI correctly identified 113 out of 116 segments with a sensitivity of 97.4%. Thrombus SNR was 153±57 and 261±95 for group 1(n=10) and group 2(n=13), respectively(P<0.01). Thrombus to lumen CNR was 149±57 and 256±94 for group 1 and group 2. Thrombus to brain tissue CNR was 41±36 and 120±63 (P<0.01), respectively. Quantification of thrombus volume was successfully conducted in all patients with CVT, and mean volume of thrombus was 10.5±6.9cc. Conclusions The current findings support that with effectively suppressed blood signal, MRBTI allows selective visualization of thrombus as opposed to indirect detection of venous flow perturbation and can be used as a promising first line diagnostic imaging tool. PMID:26670082

  7. Lnk regulates integrin αIIbβ3 outside-in signaling in mouse platelets, leading to stabilization of thrombus development in vivo

    PubMed Central

    Takizawa, Hitoshi; Nishimura, Satoshi; Takayama, Naoya; Oda, Atsushi; Nishikii, Hidekazu; Morita, Yohei; Kakinuma, Sei; Yamazaki, Satoshi; Okamura, Satoshi; Tamura, Noriko; Goto, Shinya; Sawaguchi, Akira; Manabe, Ichiro; Takatsu, Kiyoshi; Nakauchi, Hiromitsu; Takaki, Satoshi; Eto, Koji

    2009-01-01

    The nature of the in vivo cellular events underlying thrombus formation mediated by platelet activation remains unclear because of the absence of a modality for analysis. Lymphocyte adaptor protein (Lnk; also known as Sh2b3) is an adaptor protein that inhibits thrombopoietin-mediated signaling, and as a result, megakaryocyte and platelet counts are elevated in Lnk–/– mice. Here we describe an unanticipated role for Lnk in stabilizing thrombus formation and clarify the activities of Lnk in platelets transduced through integrin αIIbβ3–mediated outside-in signaling. We equalized platelet counts in wild-type and Lnk–/– mice by using genetic depletion of Lnk and BM transplantation. Using FeCl3- or laser-induced injury and in vivo imaging that enabled observation of single platelet behavior and the multiple steps in thrombus formation, we determined that Lnk is an essential contributor to the stabilization of developing thrombi within vessels. Lnk–/– platelets exhibited a reduced ability to fully spread on fibrinogen and mediate clot retraction, reduced tyrosine phosphorylation of the β3 integrin subunit, and reduced binding of Fyn to integrin αIIbβ3. These results provide new insight into the mechanism of αIIbβ3-based outside-in signaling, which appears to be coordinated in platelets by Lnk, Fyn, and integrins. Outside-in signaling modulators could represent new therapeutic targets for the prevention of cardiovascular events. PMID:20038804

  8. Wilms' tumor with vena caval, atrial, and middle hepatic vein tumor thrombus.

    PubMed

    Sripathi, V; Muralidharan, K V; Ramesh, S; Muralinath, S

    2000-01-01

    A 3-year-old male with a right-sided Wilms' tumor presented with tender hepatomegaly and bilateral lower-limb edema. Ultrasound and echocardiography showed a massive tumor thrombus completely occluding the inferior vena cava, right atrial cavity, and extending retrogradely into the middle hepatic vein. Two courses of preoperative chemotherapy (vincristine, actinomycin D, adriamycin) caused minimal shrinkage of the thrombus. The tumor and thrombus were successfully removed with the patient under cardiopulmonary bypass and deep hypothermic circulatory arrest followed by multiagent chemotherapy (vincristine, actinomycin D, adriamycin, cyclophosphamide). The child is alive and well with no evidence of disease 15 months later. Occlusion of the hepatic vein by a tumor thrombus in Wilms' tumor is a very rare event. It was completely removed by the right atrial route under direct vision in this child.

  9. Carboxylic acid accelerated formation of diesters

    DOEpatents

    Tustin, G.C.; Dickson, T.J.

    1998-04-28

    This invention pertains to accelerating the rate of formation of 1,1-dicarboxylic esters from the reaction of an aldehyde with a carboxylic acid anhydride or a ketene in the presence of a non-iodide containing a strong Bronsted acid catalyst by the addition of a carboxylic acid at about one bar pressure and between about 0 and 80 C in the substantial absence of a hydrogenation or carbonylation catalyst.

  10. Fibrin d-dimer concentration, deep vein thrombosis symptom duration, and venous thrombus volume.

    PubMed

    Kurklinsky, Andrew K; Kalsi, Henna; Wysokinski, Waldemar E; Mauck, Karen F; Bhagra, Anjali; Havyer, Rachel D; Thompson, Carrie A; Hayes, Sharonne N; McBane, Robert D

    2011-04-01

    To determine the relationship between fibrin D-dimer levels, symptom duration, and thrombus volume, consecutive patients with incident deep venous thrombosis (DVT) were evaluated. In a cross-sectional study design, patient symptom onset was determined by careful patient questioning. Venous thrombosis was confirmed by compression duplex ultrasonography. Thrombus volume was estimated based on patient's femur length using a forensic anthropology method. Fibrin D-dimer was measured by latex immunoassay. 72 consecutive patients with confirmed leg DVT agreed to participate. The median symptom duration at the time of diagnosis was 10 days. The median D-dimer concentration was 1050 ng/dL. The median thrombus volume was 12.92 cm(3). D-Dimer levels correlated with estimated thrombus volume (P < .0006 CI 0.12-0.41; R(2) (adjusted) = .15) but not symptom duration, patient's age, or gender. Despite varying symptom duration prior to diagnosis, fibrin D-dimer remains a sensitive measure of venous thrombosis and correlates with thrombus volume.

  11. Measurement of thrombus resolution using three-dimensional ultrasound assessment of deep vein thrombosis volume.

    PubMed

    Zhao, Limin; Prior, Steven J; Kampmann, Meghan; Sorkin, John D; Caldwell, Kevin; Braganza, Melita; McEvoy, Sue; Lal, Brajesh K

    2014-04-01

    Current imaging techniques are limited in their ability to quantify thrombus burden, progression, resolution, and organization over time in patients with acute deep vein thrombosis (DVT). These assessments are critical measures of therapeutic success when thrombolytic or thrombectomy treatment protocols are utilized for DVT. We evaluated the reliability of a new, commercially available method of acquiring and analyzing three-dimensional (3D) ultrasound images of DVTs that measures thrombus volume and echogenicity. We studied 25 consecutive hospital in-patients (18 male, seven female; age range, 37-87 years) with a first episode of acute DVT. Treatment decisions were not influenced by the study protocol. Scanning was performed independently by two sonographers, then the first sonographer repeated the scan. A combination of routine imaging in grayscale, color-flow, and power-Doppler modes (2D transducer) along with volumetric imaging (3D transducer) was performed. Patients underwent imaging at baseline and on one or more follow-up days 7, 14, 21 and 30. Image-processing software loaded on the ultrasound machine was used to obtain thrombus volume and echogenicity measurements. Thrombus volume was reliably determined by our protocol. The median volume of thrombus at baseline was 0.4 cm(3). Mean inter- and intraobserver differences in volume measurements were 0.006 ± 0.26 cm(3) and -0.12 ± 0.29 cm(3) (mean ± standard deviation). Thrombus resolved over time at a rate of -0.042 ± 0.01 cm(3)/day (P < .003). The median echogenicity of thrombus at baseline expressed as the grayscale median value was 59. There was a trend for thrombus organization (measured as echogenicity) to increase with time, +0.36 ± 0.23 grayscale median units/day (P < .13). Adjustment for the use of anticoagulation, gender of subject, or location of DVT in the upper vs lower extremity did not alter the relationship between time and volume or time and echogenicity. We describe a 3D

  12. Retrievable Inferior Vena Cava Filters in Trauma Patients: Prevalence and Management of Thrombus Within the Filter.

    PubMed

    Pan, Y; Zhao, J; Mei, J; Shao, M; Zhang, J; Wu, H

    2016-12-01

    The incidence of thrombus was investigated within retrievable filters placed in trauma patients with confirmed DVT at the time of retrieval and the optimal treatment for this clinical scenario was assessed. A technique called "filter retrieval with manual negative pressure aspiration thrombectomy" for management of filter thrombus was introduced and assessed. The retrievable filters referred for retrieval between January 2008 and December 2015 were retrospectively reviewed to determine the incidence of filter thrombus on a pre-retrieval cavogram. The clinical outcomes of different managements for thrombus within filters were recorded and analyzed. During the study 764 patients having Aegisy Filters implanted were referred for filter removal, from which 236 cases (134 male patients, mean age 50.2 years) of thrombus within the filter were observed on initial pre-retrieval IVC venogram 12-39 days after insertion (average 16.9 days). The incidence of infra-filter thrombus was 30.9%, and complete occlusion of the filter bearing IVC was seen in 2.4% (18) of cases. Retrieval was attempted in all 121 cases with small clots using a regular snare and sheath technique, and was successful in 120. A total of 116 cases with massive thrombus and IVC occlusion by thrombus were treated by CDT and/or the new retrieval technique. Overall, 213 cases (90.3%) of thrombus in the filter were removed successfully without PE. A small thrombus within the filter can be safely removed without additional management. CDT for reduction of the clot burden in filters was effective and safe. Filter retrieval with manual negative pressure aspiration thrombectomy seemed reasonable and valuable for management of massive thrombus within filters in some patients. Full assessment of the value and safety of this technique requires additional studies. Copyright © 2016 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  13. Real-Time Observation of Thrombus Growth Process in an Impeller of a Hydrodynamically Levitated Centrifugal Blood Pump by Near-Infrared Hyperspectral Imaging.

    PubMed

    Sakota, Daisuke; Murashige, Tomotaka; Kosaka, Ryo; Fujiwara, Tatsuki; Nishida, Masahiro; Maruyama, Osamu

    2015-08-01

    Understanding the thrombus formation in cardiovascular devices such as rotary blood pumps is the most important issue in developing more hemocompatible devices. The objective of this study was to develop a hyperspectral imaging (HSI) method to visualize the thrombus growth process within a rotary blood pump and investigate the optical properties of the thrombus. An in vitro thrombogenic test was conducted using fresh porcine blood and a specially designed hydrodynamically levitated centrifugal blood pump with a transparent bottom. The pump rotating at 3000 rpm circulated the blood at 1.0 L/min. The bottom surface of the pump was illuminated with white light pulsed at the same frequency as the pump rotation, and the backward-scattered light was imaged using the HSI system. Using stroboscopic HSI and an image construction algorithm, dynamic spectral imaging at wavelengths ranging from 608 to 752 nm within the rotating pump was achieved. After completing the experiment, we collected the red thrombus formed in the pump impeller and quantified the thrombus hemoglobin concentration (Hbthrombus ). The spectrum changed around the center of the impeller, and the area of change expanded toward the impeller flow path. The shape corresponded approximately to the shape of the thrombus. The spectrum change indicated that the light scattering derived from red blood cells decreased. The Hbthrombus was 4.7 ± 1.3 g/dL versus a total hemoglobin of 13 ± 0.87 g/dL. The study revealed that Hbthrombus was reduced by the surrounding blood flow. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  14. Carboxylic acid accelerated formation of diesters

    DOEpatents

    Tustin, Gerald Charles; Dickson, Todd Jay

    1998-01-01

    This invention pertains to accelerating the rate of formation of 1,1-dicarboxylic esters from the reaction of an aldehyde with a carboxylic acid anhydride or a ketene in the presence of a non-iodide containing a strong Bronsted acid catalyst by the addition of a carboxylic acid at about one bar pressure and between about 0.degree. and 80.degree. C. in the substantial absence of a hydrogenation or carbonylation catalyst.

  15. High fidelity computational simulation of thrombus formation in Thoratec HeartMate II continuous flow ventricular assist device

    PubMed Central

    Wu, Wei-Tao; Yang, Fang; Wu, Jingchun; Aubry, Nadine; Massoudi, Mehrdad; Antaki, James F.

    2016-01-01

    Continuous flow ventricular assist devices (cfVADs) provide a life-saving therapy for severe heart failure. However, in recent years, the incidence of device-related thrombosis (resulting in stroke, device-exchange surgery or premature death) has been increasing dramatically, which has alarmed both the medical community and the FDA. The objective of this study was to gain improved understanding of the initiation and progression of thrombosis in one of the most commonly used cfVADs, the Thoratec HeartMate II. A computational fluid dynamics simulation (CFD) was performed using our recently updated mathematical model of thrombosis. The patterns of deposition predicted by simulation agreed well with clinical observations. Furthermore, thrombus accumulation was found to increase with decreased flow rate, and can be completely suppressed by the application of anticoagulants and/or improvement of surface chemistry. To our knowledge, this is the first simulation to explicitly model the processes of platelet deposition and thrombus growth in a continuous flow blood pump and thereby replicate patterns of deposition observed clinically. The use of this simulation tool over a range of hemodynamic, hematological, and anticoagulation conditions could assist physicians to personalize clinical management to mitigate the risk of thrombosis. It may also contribute to the design of future VADs that are less thrombogenic. PMID:27905492

  16. [Recurrent right atrial thrombus in a patient with atrial fibrillation and heart failure].

    PubMed

    Elikowski, Waldemar; Wróblewski, Dariusz; Małek-Elikowska, Małgorzata; Mazurek, Andrzej; Foremska-Iciek, Joanna; Łazowski, Stanisław

    2015-11-01

    Atrial fibrillation and heart failure are factors predisposing to locally formed intracardiac thrombosis, which is usually localized in left-sided chambers. A case report. The authors present a case of a 50-year-old male with permanent atrial fibrillation and dilated cardiomyopathy in whom recurrent right atrial thrombus was observed. Initially, the lesion was detected in echocardiography while he was hospitalized due to extensive right-sided pneumonia. The thrombus was successfully treated with heparin, followed by warfarin. Even though the patient continued warfarin use properly, there was recurrence of the thrombus two years later during a new episode of heart failure exacerbation. Because the thrombus was resistant to intensified anticoagulation, cardiac surgery was needed. A large (30 x 25 mm) pedunculated thrombus, as well as two smaller ones (each of 10 x 10 mm) attached closely to the atrial wall and previously not detected either by echocardiography or by magnetic resonance imaging, were excited. A partially organized pattern of the thrombi in histological examination can explain lack of anticoagulation effectiveness. © 2015 MEDPRESS.

  17. The role of intraluminal thrombus on oxygen transport in abdominal aortic aneurysms

    NASA Astrophysics Data System (ADS)

    Madhavan, Sudharsan; Cherry Kemmerling, Erica

    2017-11-01

    Abdominal aortic aneurysm is ranked as the 13th leading cause of death in the United States. The presence of intraluminal thrombus is thought to cause hypoxia in the vessel wall eventually aggravating the condition. Our work investigates oxygen transport and consumption in a patient-specific model of an abdominal aortic aneurysm. The model includes intraluminal thrombus and consists of the abdominal aorta, renal arteries, and iliac arteries. Oxygen transport to and within the aortic wall layer was modeled, accounting for oxygen consumption and diffusion. Flow and transport in the lumen layer were modeled using coupled Navier-Stokes and scalar transport equations. The thrombus layer was assumed to be biomechanically inactive but permeable to oxygen transport in accordance with previously-measured diffusion coefficients. Plots of oxygen concentration through the layers illustrating reduced oxygen supply to the vessel walls in parts of the model that include thrombus will be presented.

  18. Visualization and Analysis of Biomaterial-Centered Thrombus Formation within a Defined Crevice Under Flow

    PubMed Central

    Jamiolkowski, Megan A.; Pedersen, Drake D.; Wu, Wei-Tao; Antaki, James F.; Wagner, William R.

    2016-01-01

    The blood flow pathway within a device, together with the biomaterial surfaces and status of the patient’s blood, are well-recognized factors in the development of thrombotic deposition and subsequent embolization. Blood flow patterns are of particular concern for devices such as blood pumps (i.e. ventricular assist devices, VADs) where shearing forces can be high, volumes are relatively large, and the flow fields can be complex. However, few studies have examined the effect of geometric irregularities on thrombus formation on clinically relevant opaque materials under flow. The objective of this study was to quantify human platelet deposition onto Ti6Al4V alloys, as well as positive and negative control surfaces, in the region of defined crevices (~50–150 µm in width) that might be encountered in many VADs or other cardiovascular devices. To achieve this, reconstituted fresh human blood with hemoglobin-depleted red blood cells (to achieve optical clarity while maintaining relevant rheology), long working optics, and a custom designed parallel plate flow chamber were employed. The results showed that the least amount of platelet deposition occurred in the largest crevice size examined, which was counterintuitive. The greatest levels of deposition occurred in the 90 µm and 53 µm crevices at the lower wall shear rate. The results suggest that while crevices may be unavoidable in device manufacturing, the crevice size might be tailored, depending on the flow conditions, to reduce the risk of thromboembolic events. Further, these data might be used to improve the accuracy of predictive models of thrombotic deposition in cardiovascular devices to help optimize the blood flow path and reduce device thrombogenicity. PMID:27156141

  19. Flow-mediated transport around a macroscopic arterial thrombus

    NASA Astrophysics Data System (ADS)

    Mukherjee, Debanjan; Garduno, Jocelyn; Shadden, Shawn

    2017-11-01

    Pathological blood clotting (thrombosis) is the acute cause of most major cardiovascular events including heart attack and stroke. Local blood and plasma transport in the neighborhood of a clot is thought to govern the thrombotic process (e.g. growth and consolidation), embolization, and the effectiveness of pharmacological treatments. To better understand the fluid mechanics near a clot it is necessary to resolve the dynamic interactions between a realistic thrombus with arbitrary shape and microstructure, and viscous, pulsatile flow. Here, we describe a computational technique to characterize flow-mediated transport phenomena in the vicinity of macro-scale arterial clots. The technique comprises (a) resolving unsteady flow around a thrombus model using a discrete particle fictitious domain finite element method; (b) identifying coherent transport features using finite time Lyapunov exponent fields, and (c) characterizing mixing using a particle-based approach. Numerical examples are discussed using realistic thrombus aggregates derived from experimental data, and pulsatile flow typical in human arteries. The results indicate the existence of local transport barriers and coherent regions in the vicinity of the clot with potential influence to local biochemical mechanics. National Science Foundation Award: 1354541; American Heart Association Award: 16POST27500023.

  20. LX0702, a novel snake venom peptide derivative, inhibits thrombus formation via affecting the binding of fibrinogen with GPIIb/IIIa.

    PubMed

    Kong, Yi; Wang, Ying; Yang, Wei; Xie, Zhouling; Li, Zhiyu

    2015-04-01

    Based on the structure of AAP, a novel anti-thrombotic peptide from snake venom which we discovered in our previous study, more than 60 compounds were designed and synthesized. One of these termed as LX0702 exhibited stronger anti-platelet aggregation activity than AAP. This study aims to investigate the effects of LX0702 on anti-thrombotic formation and its underlying mechanism. We found that LX0702 inhibited platelet aggregation induced by ADP, thrombin and collagen in a dose dependent manner, with IC50 values of 49.90 ± 2.03, 50.65 ± 0.34 and 83.90 ± 2.06 μM, respectively. It also inhibited thrombus formation in the rat arterio-venous shunt model. In addition, the effect of LX0702 on hemostasis system was tested. Compared to control saline, bleeding time was not prolonged. Furthermore, the ELISA revealed that LX0702 inhibited fibrinogen binding with GPIIb/IIIa in a dose dependent manner with an IC50 value of 1.26 ± 0.13 μM. These findings clearly demonstrate that LX0702 has anti-platelet/anti-thrombotic effects without increased bleeding risk. Therefore it might be developed into an effective drug for the prevention or treatment of thrombotic diseases. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  1. Novel Percutaneous Radiofrequency Ablation of Portal Vein Tumor Thrombus: Safety and Feasibility

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mizandari, Malkhaz; Ao, Guokun; Zhang Yaojun

    2013-02-15

    We report our experience of the safety of partial recanalization of the portal vein using a novel endovascular radiofrequency (RF) catheter for portal vein tumor thrombosis. Six patients with liver cancer and tumor thrombus in the portal vein underwent percutaneous intravascular radiofrequency ablation (RFA) using an endovascular bipolar RF device. A 0.035-inch guidewire was introduced into a tributary of the portal vein and through which a 5G guide catheter was introduced into the main portal vein. After manipulation of the guide catheter over the thrombus under digital subtraction angiography, the endovascular RF device was inserted and activated around the thrombus.more » There were no observed technique specific complications, such as hemorrhage, vessel perforation, or infection. Post-RFA portography showed partial recanalization of portal vein. RFA of portal vein tumor thrombus in patients with hepatocellular carcinoma is technically feasible and warrants further investigation to assess efficacy compared with current recanalization techniques.« less

  2. A thrombus in transit through a patent foramen ovale.

    PubMed

    Ibebuogu, Uzoma N; Khouzam, Rami N; Sharma, Gyanendra; Thornton, John W; Robati, Roshanak; Silverman, David

    2014-10-01

    Patent foramen ovale (PFO) is a congenital heart defect that may first be diagnosed in adulthood and has a prevalence of 25% to 30%. Although many patients with PFO are asymptomatic and do not require treatment, paradoxical embolism can cause stroke or myocardial infarction. The authors report an unusual case of PFO with a transversing thrombus in an 80-year-old man. The patient's initial presentation appeared clinically as acute coronary syndrome, but he was subsequently diagnosed with a massive thrombus in transit via a PFO and pulmonary embolus leading to right-sided heart failure.

  3. The Use of Fluid Mechanics to Predict Regions of Microscopic Thrombus Formation in Pulsatile VADs.

    PubMed

    Topper, Stephen R; Navitsky, Michael A; Medvitz, Richard B; Paterson, Eric G; Siedlecki, Christopher A; Slattery, Margaret J; Deutsch, Steven; Rosenberg, Gerson; Manning, Keefe B

    2014-03-01

    We compare the velocity and shear obtained from particle image velocimetry (PIV) and computational fluid dynamics (CFD) in a pulsatile ventricular assist device (VAD) to further test our thrombus predictive methodology using microscopy data from an explanted VAD. To mimic physiological conditions in vitro , a mock circulatory loop is used with a blood analog that matched blood's viscoelastic behavior at 40% hematocrit. Under normal physiologic pressures and for a heart rate of 75 bpm, PIV data is acquired and wall shear maps are produced. The resolution of the PIV shear rate calculations are tested using the CFD and found to be in the same range. A bovine study, using a model of the 50 cc Penn State V-2 VAD, for 30 days at a constant beat rate of 75 beats per minute (bpm) provides the microscopic data whereby after the 30 days, the device is explanted and the sac surface analyzed using scanning electron microscopy (SEM) and, after immunofluorescent labeling for platelets and fibrin, confocal microscopy. Areas are examined based on PIV measurements and CFD, with special attention to low shear regions where platelet and fibrin deposition are most likely to occur. Data collected within the outlet port in a direction normal to the front wall of the VAD shows that some regions experience wall shear rates less than 500 s -1 , which increases the likelihood of platelet and fibrin deposition. Despite only one animal study, correlations between PIV, CFD, and in vivo data show promise. Deposition probability is quantified by the thrombus susceptibility potential, a calculation to correlate low shear and time of shear with deposition.

  4. Incremental value of contrast echocardiography in the evaluation of a cardiac thrombus.

    PubMed

    Po, Jose Ricardo F; Tong, Matthew S; Grove, Erica L; Biederman, Robert W W

    2017-02-01

    A 52-year-old man presented with altered mental status and report of prior complaint of chest pain. On electrocardiography, anterolateral ST-segment elevations with Q-waves in the septal leads were seen. Initial echocardiography images demonstrated a thickened anteroseptum. Further imaging showed the presence of a well-attached laminated apical thrombus. Contrast echocardiography images showed that the thrombus had minimal attachment to the endocardial surface. CT head subsequently showed the presence of acute stroke. The case demonstrates the additional value of contrast echocardiography in the evaluation of cardiac masses despite the certainty in the diagnosis of a thrombus. © 2017, Wiley Periodicals, Inc.

  5. Chronic skin inflammation accelerates macrophage cholesterol crystal formation and atherosclerosis

    PubMed Central

    Ng, Qimin; Sanda, Gregory E.; Dey, Amit K.; Teague, Heather L.; Sorokin, Alexander V.; Dagur, Pradeep K.; Silverman, Joanna I.; Harrington, Charlotte L.; Rodante, Justin A.; Rose, Shawn M.; Varghese, Nevin J.; Belur, Agastya D.; Goyal, Aditya; Gelfand, Joel M.; Springer, Danielle A.; Bleck, Christopher K.E.; Thomas, Crystal L.; Yu, Zu-Xi; Winge, Mårten C.G.; Kruth, Howard S.; Marinkovich, M. Peter; Joshi, Aditya A.; Playford, Martin P.; Mehta, Nehal N.

    2018-01-01

    Inflammation is critical to atherogenesis. Psoriasis is a chronic inflammatory skin disease that accelerates atherosclerosis in humans and provides a compelling model to understand potential pathways linking these diseases. A murine model capturing the vascular and metabolic diseases in psoriasis would accelerate our understanding and provide a platform to test emerging therapies. We aimed to characterize a new murine model of skin inflammation (Rac1V12) from a cardiovascular standpoint to identify novel atherosclerotic signaling pathways modulated in chronic skin inflammation. The RacV12 psoriasis mouse resembled the human disease state, including presence of systemic inflammation, dyslipidemia, and cardiometabolic dysfunction. Psoriasis macrophages had a proatherosclerotic phenotype with increased lipid uptake and foam cell formation, and also showed a 6-fold increase in cholesterol crystal formation. We generated a triple-genetic K14-RacV12–/+/Srb1–/–/ApoER61H/H mouse and confirmed psoriasis accelerates atherogenesis (~7-fold increase). Finally, we noted a 60% reduction in superoxide dismutase 2 (SOD2) expression in human psoriasis macrophages. When SOD2 activity was restored in macrophages, their proatherogenic phenotype reversed. We demonstrate that the K14-RacV12 murine model captures the cardiometabolic dysfunction and accelerates vascular disease observed in chronic inflammation and that skin inflammation induces a proatherosclerotic macrophage phenotype with impaired SOD2 function, which associated with accelerated atherogenesis. PMID:29321372

  6. Covered stent to exclude intravascular thrombus.

    PubMed

    Liistro, Francesco; Stankovic, Goran; Di Mario, Carlo; Montorfano, Matteo; Briguori, Carlo; Colombo, Antonio

    2002-04-01

    To describe the utility of stent-graft implantation to avoid distal embolization from a large thrombus-containing lesion. A 67-year-old man was evaluated for recent onset of disabling left leg claudication. Angiography disclosed a mobile lobular mass occluding the left common iliac artery; irregular staining suggested an atherothrombotic lesion. Through a percutaneous ipsilateral access and an 8-F sheath, a balloon-expandable Jostent peripheral stent-graft was positioned with the distal edge immediately proximal to the internal iliac artery ostium. A prominent "waist" at the center of the balloon confirmed entrapment of the thrombotic mass. Completion angiography showed an optimal result with no residual stenosis or evidence of distal embolization. At 6-month follow-up, the patient was asymptomatic with angiographically documented luminal patency and no evidence of in-stent stenosis. Stent-graft implantation appears a viable treatment alternative for thrombus-containing lesions, particularly when the thrombotic material is localized or is in a large vessel.

  7. Blood clots are rapidly assembled hemodynamic sensors: flow arrest triggers intraluminal thrombus contraction.

    PubMed

    Muthard, Ryan W; Diamond, Scott L

    2012-12-01

    Blood clots form under flow during intravascular thrombosis or vessel leakage. Prevailing hemodynamics influence thrombus structure and may regulate contraction processes. A microfluidic device capable of flowing human blood over a side channel plugged with collagen (± tissue factor) was used to measure thrombus permeability (κ) and contraction at controlled transthrombus pressure drops. The collagen (κ(collagen)=1.98 × 10(-11) cm(2)) supported formation of a 20-µm thick platelet layer, which unexpectedly underwent massive platelet retraction on flow arrest. This contraction resulted in a 5.34-fold increase in permeability because of collagen restructuring. Without stopping flow, platelet deposits (no fibrin) had a permeability of κ(platelet)=5.45 × 10(-14) cm(2) and platelet-fibrin thrombi had κ(thrombus)=2.71 × 10(-14) cm(2) for ΔP=20.7 to 23.4 mm Hg, the first ever measurements for clots formed under arterial flow (1130 s(-1) wall shear rate). Platelet sensing of flow cessation triggered a 4.6- to 6.5-fold (n=3, P<0.05) increase in contraction rate, which was also observed in a rigid, impermeable parallel-plate microfluidic device. This triggered contraction was blocked by the myosin IIA inhibitor blebbistatin and by inhibitors of thromboxane A2 (TXA(2)) and ADP signaling. In addition, flow arrest triggered platelet intracellular calcium mobilization, which was blocked by TXA(2)/ADP inhibitors. As clots become occlusive or blood pools following vessel leakage, the flow diminishes, consequently allowing full platelet retraction. Flow dilution of ADP and thromboxane regulates platelet contractility with prevailing hemodynamics, a newly defined flow-sensing mechanism to regulate clot function.

  8. Role of intramural platelet thrombus in the pathogenesis of wall rupture and intra-ventricular thrombosis following acute myocardial infarction.

    PubMed

    Du, Xiao-Jun; Shan, Leonard; Gao, Xiao-Ming; Kiriazis, Helen; Liu, Yang; Lobo, Abhirup; Head, Geoffrey A; Dart, Anthony M

    2011-02-01

    Left ventricular thrombus (LVT) and rupture are important mechanical complications following myocardial infarction (MI) and are believed to be due to unrelated mechanisms. We studied whether, in fact, wall rupture and LVT are closely related in their pathogenesis with intramural platelet thrombus (IMT) playing a pivotal role. Male 129sv and C57Bl/6 mice underwent operation to induce MI, and autopsy was performed to confirm rupture deaths. Haemodynamic features of rupture events were monitored by telemetry in conscious mice. Detailed histological examination was conducted with special attention to the presence of IMT in relation to rupture location and LVT formation. IMT was detected in infarcted hearts of 129sv (82%) and C57Bl/6 (39%) mice with rupture in the form of a narrow streak spanning the wall or an occupying mass dissecting the infarcted myofibers apart. IMT often contained dense inflammatory cells and blood clot, indicating a dynamic process of thrombus formation and destruction. Notably, IMT was found extending into the cavity to form LVT. Haemodynamic monitoring by telemetry revealed that rupture occurred either as a single event or recurrent episodes. Importantly, the anti-platelet drug clopidogrel, but not aspirin, reduced the prevalence of rupture (10% vs. 45%) and IMT, and suppressed the degree of inflammation. Thus, IMT is a key pathological element in the infarcted heart closely associated with the complications of rupture and LVT. IMT could be either triggered by a wall tear or act as initiator of rupture. IMT may propagate towards the ventricular chamber to trigger LVT.

  9. Renal cell carcinoma with inferior vena cava thrombus extending to the right atrium diagnosed during pregnancy.

    PubMed

    Ghanney, Efe C; Cavallo, Jaime A; Levin, Matthew A; Reddy, Ramachandra; Bander, Jeffrey; Mella, Maria; Stone, Joanne; Schwartz, Myron; Haines, Kenneth; Gidwani, Umesh; Mehrazin, Reza

    2017-12-01

    Only one case of renal cell carcinoma (RCC) with inferior vena cava (IVC) tumor thrombus diagnosed and treated during pregnancy has been reported in the literature. In that report, the tumor thrombus extended to the infrahepatic IVC (level II tumor thrombus). In the present case, a 37-year-old woman with lupus anticoagulant antibodies was diagnosed with RCC and IVC tumor thrombus extending to the right atrium (level IV tumor thrombus) at 24 weeks of pregnancy. The fetus was safely delivered by cesarean section at 30 weeks of gestation. At 4 days later, an open right radical nephrectomy and IVC and right atrial thrombectomy were performed on cardiopulmonary bypass (CPB) once the patient's hemodynamic status had been optimized. Fetal and maternal concerns included the risk of a thromboembolic event (due to increased hypercoagulability from pregnancy, active malignancy, and lupus anticoagulant), intraoperative hemorrhage risk (due to extensive venous collaterals and anticoagulation), and fetal morbidity and mortality (due to fetal lung immaturity). Standardized guidelines for treatment of RCC with or without IVC tumor thrombus during pregnancy are unavailable due to the infrequency of such cases. Treatment decisions are therefore individualized and this case report may inform the management of future patients diagnosed with RCC with level IV tumor thrombus during pregnancy.

  10. An integrated fluid-chemical model toward modeling the formation of intra-luminal thrombus in abdominal aortic aneurysms.

    PubMed

    Biasetti, Jacopo; Spazzini, Pier Giorgio; Swedenborg, Jesper; Gasser, T Christian

    2012-01-01

    Abdominal Aortic Aneurysms (AAAs) are frequently characterized by the presence of an Intra-Luminal Thrombus (ILT) known to influence their evolution biochemically and biomechanically. The ILT progression mechanism is still unclear and little is known regarding the impact of the chemical species transported by blood flow on this mechanism. Chemical agonists and antagonists of platelets activation, aggregation, and adhesion and the proteins involved in the coagulation cascade (CC) may play an important role in ILT development. Starting from this assumption, the evolution of chemical species involved in the CC, their relation to coherent vortical structures (VSs) and their possible effect on ILT evolution have been studied. To this end a fluid-chemical model that simulates the CC through a series of convection-diffusion-reaction (CDR) equations has been developed. The model involves plasma-phase and surface-bound enzymes and zymogens, and includes both plasma-phase and membrane-phase reactions. Blood is modeled as a non-Newtonian incompressible fluid. VSs convect thrombin in the domain and lead to the high concentration observed in the distal portion of the AAA. This finding is in line with the clinical observations showing that the thickest ILT is usually seen in the distal AAA region. The proposed model, due to its ability to couple the fluid and chemical domains, provides an integrated mechanochemical picture that potentially could help unveil mechanisms of ILT formation and development.

  11. Experimental pulmonary embolism: effects of the thrombus and attenuation of pulmonary artery injury by low-molecular-weight heparin.

    PubMed

    Rectenwald, John E; Deatrick, K Barry; Sukheepod, Pasu; Lynch, Erin M; Moore, Andrea J; Moaveni, Daria M; Dewyer, Nicholas A; Deywer, Nicholas A; Luke, Catherine E; Upchurch, Gilbert R; Wakefield, Thomas W; Kunkel, Steven L; Henke, Peter K

    2006-04-01

    Pulmonary embolism (PE) is a life-threatening condition that is associated with the long-term sequelae of chronic pulmonary hypertension. Prior experimental work has suggested that post-PE inflammation is accompanied by pulmonary artery intimal hyperplasia. This study evaluated the effect of the thrombus and tested the hypothesis that thrombolytic, antiplatelet, and anticoagulant agents would decrease pulmonary injury. Male Sprague-Dawley rats (n = 267) underwent laparotomy and temporary clip occlusion of the infrarenal inferior vena cava for the formation of endogenous thrombus or placement of an inert silicone "thrombus." Two days later, repeat laparotomy was performed, the clip removed, and the thrombus or silicone plug was embolized to the lungs. The endogenous thrombus group received normal saline, low-molecular-weight heparin (LMWH), tissue plasminogen activator (tPA), or a gIIB/IIIA antagonist (abciximab). Lung tissue was harvested at various times over 21 days and assayed for total collagen, monocyte chemoattractant protein-1 (MCP-1), interleukin-13 (IL-13), and transforming growth factor-beta (TGF-beta). Fixed sections were stained with trichrome for intimal hyperplasia determination and ED-1 monocytes and alpha-actin-positive staining. The overall survival for rats undergoing PE was 90%, was not affected by treatment, and 84% of all PE localized to the right pulmonary artery. The PE significantly reduced Pa(O2) in all groups. Compared with controls, the silicone emboli group had an increased level of IL-13 on day 1, an increased level of MCP-1 on day 4, and an increase in the levels of all inflammatory mediators on day 14 (P < .05). Accompanying these differences were greater pulmonary artery intimal hyperplasia at days 4 and 21 in the silicone group compared with controls (P < .05). LMWH treatment in the thrombus of PE rats significantly decreased IL-13 levels at all time points, whereas treatment with abciximab or tPA significantly increased IL-13

  12. Successful treatment of central venous catheter induced superior vena cava syndrome with ultrasound accelerated catheter-directed thrombolysis.

    PubMed

    Dumantepe, Mert; Tarhan, Arif; Ozler, Azmi

    2013-06-01

    Superior vena cava (SVC) syndrome results from obstruction of flow through the vessel either by external compression or thrombosis. External compression by intrathoracic neoplasms is the most common etiology, especially lung cancer and lymphoma. Thrombosis is becoming increasingly common due to the use of indwelling catheters and implantable central venous access devices. Most patients are unresponsive to anticoagulation alone which appears to be effective only in the mildest cases. However, recent advances in catheter-based interventions have led to the development of a variety of minimally invasive endovascular strategies to remove venous thrombus and accepted as an important first-line treatment given its high overall success rate and low morbidity as compared with medical and surgical treatments. Ultrasound accelerated catheter-directed thrombolysis (UACDT) has been developed to rapidly and completely resolve the existing thrombus. This technique integrates high frequency, low intensity ultrasound (US) with standard CDT in order to accelerate clot dissolution, reducing treatment time and the incidence of thrombolysis-related complications. An US wave enhances drug permeation through thrombus by disaggregating the fibrin matrix, exposing additional plasminogen receptor sites to the thrombolytic agent. The US energy affects thrombus in the entire venous segment, increasing the probability of complete thrombus clearing. We report the case of a 56-year-old man who presented with a 5 days history of SVC syndrome symptoms who had been receiving chemotherapy for colon cancer through a right subclavian vein port catheter. The patient successfully treated with UACDT with EkoSonic(®) Mach4e Endovascular device with an overnight infusion. © 2013 Wiley Periodicals, Inc. Copyright © 2013 Wiley Periodicals, Inc.

  13. [Clinical analysis of patients with lower extremity deep venous thrombosis complicated with inferior vena cava thrombus].

    PubMed

    Dong, Dian-ning; Wu, Xue-jun; Zhang, Shi-yi; Zhong, Zhen-yue; Jin, Xing

    2013-06-04

    To explore the clinical profiles of patients with lower extremity deep venous thrombosis (DVT) complicated with inferior vena cava (IVC) thrombus and summarize their clinical diagnostic and therapeutic experiences. The clinical characteristics, diagnosis and treatment of 20 hospitalized patients with DVT complicated with inferior vena cava thrombus were analyzed retrospectively. All of them were of proximal DVT. There were phlegmasia cerulea dolens (n = 3), pulmonary embolism (n = 3) and completely occlusion of IVC (n = 5). Clinical manifestations were severe. Retrievable inferior vena cava filter (IVCF) was implanted for 17 cases. Catheter-directed thrombolysis (CDT) through ipsilateral popliteal vein was applied for 7 cases and systemic thrombolysis therapy for 8 cases. The effective rate of thrombolysis for fresh IVC thrombus was 100%. Among 5 cases with Cockett Syndrome, 3 cases underwent balloon dilatation angioplasty and endovascular stenting of iliac vein. And 17 IVCFs were retrieved successfully within 3 weeks. IVC thrombus disappeared completely in 15 cases. Systemic or local thrombolysis with protective IVCF is a safe and effective therapy for nonocclusive IVC thrombus in DVT. And CDT is recommended for symptomatic occlusive IVC thrombus.

  14. Coronary intervention in thrombus-rich lesions: beyond stents and glycoprotein IIb/IIIa inhibitors.

    PubMed

    Halkin, Amir; Keren, Gad; Stone, Gregg W; Holmes, David R; Rosenschein, Uri

    2003-11-01

    Despite widespread use of stents and GP IIb/IIIa antagonists, complications following percutaneous treatment of thrombus-rich lesions continue to plague patients with ACS. In these patients the angiographically evident coronary thrombosis may represent a high degree of thrombus burden, which leads to a higher level of microembolization and its clinical sequelae. New catheter-based thrombus burden reduction systems and distal protection devices show promise for improving the prognosis of these high risk patients by decreasing distal microembolization, and thereby preventing myonecrosis. Careful procedural timing and patient selection are also likely to improve outcomes and resource utilization in the management of ACS patients.

  15. Quantity of residual thrombus after successful catheter-directed thrombolysis for iliofemoral deep venous thrombosis correlates with recurrence.

    PubMed

    Aziz, F; Comerota, A J

    2012-08-01

    Iliofemoral deep venous thrombosis (IFDVT) is an independent risk factor for recurrent DVT. It has been observed that recurrent DVT correlates with residual thrombus. This study evaluates whether risk of recurrence is related to the amount of residual thrombus following catheter-directed thrombolysis (CDT) for IFDVT. Patients who underwent CDT for IFDVT had their degree of lysis quantified by a reader blind to the patients' long-term clinical outcome. Patients were classified into two groups, ≥50% and <50% residual thrombus. Recurrence was defined as a symptomatic presentation with image verification of new or additional thrombus. A total of 75 patients underwent CDT for IFDVT. Median follow-up was 35.9 months. Sixty-eight patients (91%) had no evidence of recurrence and seven (9%) developed recurrence. Of the patients who had ≥50% (mean 80%) residual thrombus, 50% (4/8) experienced recurrence, but in those with <50% (mean 35%) residual thrombus, only 5% (3/67) had recurrent DVT (P = 0.0014). The burden of residual thrombus at completion of CDT correlates with the risk of DVT recurrence. Patients having CDT for IFDVT had a lower risk of recurrence than expected. Successful clearing of acute clot in IFDVT patients significantly reduces the recurrence risk compared to patients with a large residual thrombus burden. Copyright © 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  16. Solid-particle jet formation under shock-wave acceleration.

    PubMed

    Rodriguez, V; Saurel, R; Jourdan, G; Houas, L

    2013-12-01

    When solid particles are impulsively dispersed by a shock wave, they develop a spatial distribution which takes the form of particle jets whose selection mechanism is still unidentified. The aim of the present experimental work is to study particle dispersal with fingering effects in an original quasi-two-dimensional experiment facility in order to accurately extract information. Shock and blast waves are generated in the carrier gas at the center of a granular medium ring initially confined inside a Hele-Shaw cell and impulsively accelerated. With the present experimental setup, the particle jet formation is clearly observed. From fast flow visualizations, we notice, in all instances, that the jets are initially generated inside the particle ring and thereafter expelled outward. This point has not been observed in three-dimensional experiments. We highlight that the number of jets is unsteady and decreases with time. For a fixed configuration, considering the very early times following the initial acceleration, the jet size selection is independent of the particle diameter. Moreover, the influence of the initial overpressure and the material density on the particle jet formation have been studied. It is shown that the wave number of particle jets increases with the overpressure and with the decrease of the material density. The normalized number of jets as a function of the initial ring acceleration shows a power law valid for all studied configurations involving various initial pressure ratios, particle sizes, and particle materials.

  17. The accelerating pace of star formation

    NASA Astrophysics Data System (ADS)

    Caldwell, Spencer; Chang, Philip

    2018-03-01

    We study the temporal and spatial distribution of star formation rates in four well-studied star-forming regions in local molecular clouds (MCs): Taurus, Perseus, ρ Ophiuchi, and Orion A. Using published mass and age estimates for young stellar objects in each system, we show that the rate of star formation over the last 10 Myr has been accelerating and is (roughly) consistent with a t2 power law. This is in line with previous studies of the star formation history of MCs and with recent theoretical studies. We further study the clustering of star formation in the Orion nebula cluster. We examine the distribution of young stellar objects as a function of their age by computing an effective half-light radius for these young stars subdivided into age bins. We show that the distribution of young stellar objects is broadly consistent with the star formation being entirely localized within the central region. We also find a slow radial expansion of the newly formed stars at a velocity of v = 0.17 km s-1, which is roughly the sound speed of the cold molecular gas. This strongly suggests the dense structures that form stars persist much longer than the local dynamical time. We argue that this structure is quasi-static in nature and is likely the result of the density profile approaching an attractor solution as suggested by recent analytic and numerical analysis.

  18. Ultrasound active nanoscaled lipid formulations for thrombus lysis.

    PubMed

    Becker, Andreas; Marxer, Elena; Brüssler, Jana; Hoormann, Anne Sophia; Kuhnt, Daniela; Bakowsky, Udo; Nimsky, Christopher

    2011-04-01

    In the present study, we investigated the sonothrombolytic effect of new nanoscaled lipid formulations in human blood clots, using diagnostic ultrasound. Human blood clots of 1 ml were incubated with 1 μl of the different lipid dispersions DPPC/CH, DPPC/PEG40S, DSPC/PEG40S and the commercially available ultrasound contrast agent SonoVue®. Clots were stored for 3 days at 5 °C to obtain maximal clot retraction and lytic resistance. Each clot weight was determined before and after continuous insonation for 1h of insonation at 1.4 MHz. The pressure in the insonation chamber was 80 mm Hg to mimic middle arterial blood pressure. There were no significant differences in thrombus weight before insonation. All nanoscaled formulations and SonoVue® were able to reduce thrombus weight compared to the weight loss of clots that were not insonated but kept under pressure for one hour (p < 0.001). We found a highly significant weight reduction with DSPC/PEG40S compared to SonoVue® (p = 0.007). Nanoscaled DSPC/PEG40S dispersion could be a promising formulation in ultrasound enhanced thrombolysis even without thrombolytic drugs. Stable cavitation is a crucial parameter in fragmentation of thrombus architecture. Further studies of physicochemical properties of DSPC/PEG40S are necessary to corroborate our hypothesis. Copyright © 2010 Elsevier B.V. All rights reserved.

  19. Left atrial thrombus as an early consequence of blunt chest trauma

    PubMed Central

    Mahy, I; Al-Mohammad, A; Cargill, R

    1998-01-01

    Thromboembolism is rarely considered in discussions of the complications of blunt chest trauma. The few cases of thromboembolism that have been reported in this setting have occurred in association with significant myocardial damage. A previously fit 23 year old woman was admitted to the intensive care unit following a road traffic accident. A day later, left atrial thrombus was demonstrated by transoesophageal echocardiography in the absence of any other evidence of important myocardial injury. Anticoagulation with heparin was cautiously introduced in spite of her extensive injuries, and there were no consequent bleeding complications. At hospital discharge on day 18 she was entirely well. Full anticoagulation with warfarin was continued for a further eight weeks at which time follow up transoesophageal echocardiography showed complete resolution of the thrombus.

 Keywords: blunt chest trauma;  thromboembolism;  left atrial thrombus;  transoesophageal echocardiography PMID:9538317

  20. Thrombus Aspiration in ST-Segment-Elevation Myocardial Infarction: An Individual Patient Meta-Analysis: Thrombectomy Trialists Collaboration.

    PubMed

    Jolly, Sanjit S; James, Stefan; Džavík, Vladimír; Cairns, John A; Mahmoud, Karim D; Zijlstra, Felix; Yusuf, Salim; Olivecrona, Goran K; Renlund, Henrik; Gao, Peggy; Lagerqvist, Bo; Alazzoni, Ashraf; Kedev, Sasko; Stankovic, Goran; Meeks, Brandi; Frøbert, Ole

    2017-01-10

    Thrombus aspiration during percutaneous coronary intervention (PCI) for the treatment of ST-segment-elevation myocardial infarction (STEMI) has been widely used; however, recent trials have questioned its value and safety. In this meta-analysis, we, the trial investigators, aimed to pool the individual patient data from these trials to determine the benefits and risks of thrombus aspiration during PCI in patients with ST-segment-elevation myocardial infarction. Included were large (n≥1000), randomized, controlled trials comparing manual thrombectomy and PCI alone in patients with ST-segment-elevation myocardial infarction. Individual patient data were provided by the leadership of each trial. The prespecified primary efficacy outcome was cardiovascular mortality within 30 days, and the primary safety outcome was stroke or transient ischemic attack within 30 days. The 3 eligible randomized trials (TAPAS [Thrombus Aspiration During Percutaneous Coronary Intervention in Acute Myocardial Infarction], TASTE [Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia], and TOTAL [Trial of Routine Aspiration Thrombectomy With PCI Versus PCI Alone in Patients With STEMI]) enrolled 19 047 patients, of whom 18 306 underwent PCI and were included in the primary analysis. Cardiovascular death at 30 days occurred in 221 of 9155 patients (2.4%) randomized to thrombus aspiration and 262 of 9151 (2.9%) randomized to PCI alone (hazard ratio, 0.84; 95% confidence interval, 0.70-1.01; P=0.06). Stroke or transient ischemic attack occurred in 66 (0.8%) randomized to thrombus aspiration and 46 (0.5%) randomized to PCI alone (odds ratio, 1.43; 95% confidence interval, 0.98-2.10; P=0.06). There were no significant differences in recurrent myocardial infarction, stent thrombosis, heart failure, or target vessel revascularization. In the subgroup with high thrombus burden (TIMI [Thrombolysis in Myocardial Infarction] thrombus grade ≥3), thrombus aspiration was

  1. Peripheral Distribution of Thrombus Does Not Affect Outcomes After Surgical Pulmonary Embolectomy.

    PubMed

    Pasrija, Chetan; Shah, Aakash; George, Praveen; Mohammed, Isa; Brigante, Francis A; Ghoreishi, Mehrdad; Jeudy, Jean; Taylor, Bradley S; Gammie, James S; Griffith, Bartley P; Kon, Zachary N

    2018-04-04

    Thrombus located distal to the main or primary pulmonary arteries has been previously viewed as a relative contraindication to surgical pulmonary embolectomy. We compared outcomes for surgical pulmonary embolectomy for submassive and massive pulmonary embolism (PE) in patients with central versus peripheral thrombus burden. All consecutive patients (2011-2016) undergoing surgical pulmonary embolectomy at a single center were retrospectively reviewed. Based on computed tomographic angiography of each patient, central PE was defined as any thrombus originating within the lateral pericardial borders (main or right/left pulmonary arteries). Peripheral PE was defined as thrombus exclusively beyond the lateral pericardial borders, involving the lobar pulmonary arteries or distal. The primary outcome was in-hospital and 90-day survival. 70 patients were identified: 52 (74%) with central PE and 18 (26%) with peripheral PE. Preoperative vital signs and right ventricular dysfunction were similar between the two groups. Compared to the central PE cohort, operative time was significantly longer in the peripheral PE group (191 vs. 210 minutes, p<0.005)). Median right ventricular dysfunction decreased from moderate dysfunction preoperatively to no dysfunction at discharge in both groups. Overall 90-day survival was 94%, with 100% survival in patients with submassive PE in both cohorts. This single center experience demonstrates excellent overall outcomes for surgical pulmonary embolectomy with resolution of right ventricular dysfunction, and comparable morbidity and mortality for central and peripheral PE. In an experienced center and when physiologically warranted, surgical pulmonary embolectomy for peripheral distribution of thrombus is both technically feasible and effective. Copyright © 2018. Published by Elsevier Inc.

  2. Synthetic thrombus model for in vitro studies of laser thrombolysis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hermes, R.E.; Trajkovska, K.

    1998-07-01

    Laser thrombolysis is the controlled ablation of a thrombus (blood clot) blockage in a living arterial system. Theoretical modeling of the interaction of laser light with thrombi relies on the ability to perform in vitro experiments with well characterized surrogate materials. A synthetic thrombus formulation may offer more accurate results when compared to in vivo clinical experiments. The authors describe the development of new surrogate materials based on formulations incorporating chick egg, guar gum, modified food starch, and a laser light absorbing dye. The sound speed and physical consistency of the materials were very close to porcine (arterial) and humanmore » (venous) thrombi. Photographic and videotape recordings of pulsed dye laser ablation experiments under various experimental conditions were used to evaluate the new material as compared to in vitro tests with human (venous) thrombus. The characteristics of ablation and mass removal were similar to that of real thrombi, and therefore provide a more realistic model for in vitro laser thrombolysis when compared to gelatin.« less

  3. Thrombus Aspiration in ThrOmbus containing culpRiT lesions in Non-ST-Elevation Myocardial Infarction (TATORT-NSTEMI): study protocol for a randomized controlled trial

    PubMed Central

    2013-01-01

    Background Current guidelines recommend thrombus aspiration in patients with ST-elevation myocardial infarction (STEMI); however, there are insufficient data to unequivocally support thrombectomy in patients with non-STEMI (NSTEMI). Methods/Design The TATORT-NSTEMI (Thrombus Aspiration in ThrOmbus containing culpRiT lesions in Non-ST-Elevation Myocardial Infarction) trial is a prospective, controlled, multicenter, randomized, open-label trial enrolling 460 patients. The hypothesis is that, against a background of early revascularization, adjunctive thrombectomy leads to less microvascular obstruction (MO) compared with conventional percutaneous coronary intervention (PCI) alone, as assessed by cardiac magnetic resonance imaging (CMR) in patients with NSTEMI. Patients will be randomized in a 1:1 fashion to one of the two treatment arms. The primary endpoint is the extent of late MO assessed by CMR. Secondary endpoints include early MO, infarct size, and myocardial salvage assessed by CMR as well as enzymatic infarct size and angiographic parameters, such as thrombolysis in myocardial infarction flow post-PCI and myocardial blush grade. Furthermore, clinical endpoints including death, myocardial re-infarction, target vessel revascularization, and new congestive heart failure will be recorded at 6 and 12 months. Safety will be assessed by the incidence of bleeding and stroke. Summary The TATORT-NSTEMI trial has been designed to test the hypothesis that thrombectomy will improve myocardial perfusion in patients with NSTEMI and relevant thrombus burden in the culprit vessel reperfused by early PCI. Trial registration The trial is registered under http://www.clinicaltrials.gov: NCT01612312. PMID:23782681

  4. Thrombus organization and healing in an experimental aneurysm model. Part II. The effect of various types of bioactive bioabsorbable polymeric coils.

    PubMed

    Yuki, Ichiro; Lee, Daniel; Murayama, Yuichi; Chiang, Alexander; Vinters, Harry V; Nismmura, Ichiro; Wang, Chiachien J; Ishii, Akira; Wu, Benjamin M; Viñuela, Fernando

    2007-07-01

    Bioabsorbable polymeric material coils are being used in the endovascular treatment of aneurysms to achieve better thrombus organization than is possible using bare platinum coils. We used immunohistochemical and molecular biological analysis techniques in experimental aneurysms implanted with three different bioabsorbable polymer coils and platinum coils. The degradation kinetics of nine polymer candidates for further analysis were first analyzed in vitro, and three materials with different degradation rates were selected. Seventy-four aneurysms were created in 37 swine using the venous pouch technique. The aneurysms were surgically implanted with one of the materials as follows (time points = 3, 7, and 14 days): Group 1, Guglielmi detachable coils (platinum); Group 2, Polysorb (90:10 polyglycolic acid [PGA]/polylactic acid); Group 3, Maxon (PGA/trimethylene carbonate); and Group 4, poly-l-lactic acid. Histological, immunohistochemical, and cDNA microarray analyses were performed on tissue specimens. Groups 1 and 4 showed minimal inflammatory response adjacent to the coil mass. In Group 2, Polysorb elicited a unique, firm granulation tissue that accelerated intraaneurysmal thrombus organization. In Group 3 intermediate inflammatory reactions were seen. Microarray analysis with Expression Analysis Sytematic Explorer software showed functional-cluster-gene activation to be increased at Day 7, preceding the histologic manifestation of polymer-induced granulation tissue at Day 14. A profile of expression changes in cytokine-related and extracellular membrane-related genes was compiled. Degradation speed was not the only factor determining the strength of the biological response. Polysorb induced an early, unique granulation tissue that conferred greater mechanical strength to the intraaneurysmal coilthrombus complex. Enhancing the formation of this polymer-induced granulation tissue may provide a new direction for improving long-term anatomical outcomes in cases

  5. Thrombus Formation After Percutaneous Catheterization and Manual Compression of the Femoral Artery in Heparinized Sheep

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kim, Young Hwan; Pavcnik, Dusan, E-mail: pavcnikd@ohsu.edu; Kakizawa, Hideyaki

    The purpose of this study was to evaluate the angiographic and histopathologic changes in the superficial femoral artery (SFA) in heparinized sheep shortly after catheterization with an 8-Fr sheath and manual compression hemostasis either with standard manual compression (SMC) or with the use of a procoagulant chitosan-based HemCon Bandage. The evaluation was done in 38 SFAs of 19 heparinized (100 mg/kg) sheep. After a 5-min catheterization with an 8-Fr sheath, a 5-min compression was applied. Follow-up angiograms to evaluate hemostasis were done immediately after release of compression and then at 2.5-min intervals until no extravasation was present. Compression was reappliedmore » between angiograms. Final angiograms were performed approximately 30 min after hemostasis and after 3 min of passive flexion and extension of sheep hind limbs. Sheep were then euthanized and SFA specimens with surrounding tissues excised for histopathologic evaluation. Both types of compression caused similar changes in the catheterized SFAs. Follow-up angiograms showed mild arterial narrowing in 14 SFAs and intraluminal clots in 9 SFAs. Histology revealed periarterial hematoma in all 38 specimens. Intraluminal thrombi consisting predominantly of platelets and fibrin were present in 32 SFAs. Their size varied from superficial elevations (8 arteries) to medium-sized, 1- to 2-mm, polypoid protrusions (15 arteries) to large polypoid clots, 3-4 mm long (9 arteries). In six SFAs, the arterial access sites were not included in the obtained specimens. In conclusion, hemostasis with manual compression is achieved in the acute phase by formation of a predominantly platelet-fibrin thrombus occluding the arterial wall access site and often extending significantly into the arterial lumen. The healing process of arterial access sites should be explored several days after catheterization.« less

  6. Growth differentiation factor 15 is associated with left atrial/left atrial appendage thrombus in patients with nonvalvular atrial fibrillation.

    PubMed

    Hu, Xiao Feng; Zhan, Rui; Xu, Shanhu; Wang, Junjun; Wu, Jiong; Liu, Xiaoli; Li, Yaguo; Chen, Linhui

    2018-01-01

    There is evidence suggesting that growth differentiation factor 15 (GDF-15) appears to be associated with stroke in patients with atrial fibrillation (AF). AF-related thromboembolic stroke is predominantly attributed to the thrombus from the left atrium (LA) or left atrial appendage (LAA). GDF-15 is related to LA/LAA thrombus in nonvalvular AF (NVAF) patients. A total of 894 patients with NVAF without anticoagulation therapy were included in this study. All patients routinely underwent transesophageal echocardiography for detection of LA/LAA thrombus. GDF-15 was measured by enzyme-linked immunosorbent assay. Logistic regression models were used to test for association. LA/LAA thrombus was detected by transesophageal echocardiography in 69 (7.72%) patients with AF. The GDF-15 levels in the patients with LA/LAA thrombus were significantly higher than those without LA/LAA thrombus (log 10 GDF-15: 2.989 ± 0.023 ng/L vs 2.831 ± 0.007 ng/L; P < 0.001). Logistic regression analysis showed that GDF-15 was an independent risk factor for LA/LAA thrombus (odds ratio [per quarter]: 1.799, 95% confidence interval: 1.381-2.344, P < 0.001) after adjusting for potential clinical risk factors. The optimal cutoff point for GDF-15 predicting LA/LAA thrombus was 809.9 ng/L (sensitivity, 75.3%; specificity, 61.5%), determined by ROC curve. The area under the curve was 0.709 (95% confidence interval: 0.644-0.770, P < 0.001). Elevated GDF-15 indicated a significantly increased risk for LA/LAA thrombus in NVAF patients. Thus, GDF-15 might be a potentially useful adjunct in discriminating LA/LAA thrombus in NVAF patients. © 2018 Wiley Periodicals, Inc.

  7. [Stroke due to infective endocarditis diagnosed by the retrieved thrombus: a case report].

    PubMed

    Nakanishi, Kaoru; Kawano, Hiroyuki; Amano, Tatsuo; Omori, Yoshihiko; Kanma, Hiroshi; Hirano, Teruyuki

    2018-01-26

    A 80-years-old woman suddenly presented with aphasia, right hemiparesis, and dysesthesia. MRA showed the left middle cerebral artery occlusion. She was diagnosed as hyperacute ischemic stroke. She was treated with intravenous recombinant tissue plasminogen activator and underwent endovascular thrombectomy. On admission, she had a fever and high C reactive protein, and was treated with antibiotic therapy. The pathological diagnosis of the retrieved thrombus revealed the cluster of the gram positive cocci. The blood culture was negative and thransthoracic echocardiogram did not detect the vegetation. She was finally diagnosed as cardioembolic stroke due to infective endocarditis based on the pathological diagnosis of the retrieved thrombus. The pathological diagnosis of the retrieved thrombus was quite important to clarify the cause of ischemic stroke.

  8. Systematic Review of Treatment for Trapped Thrombus in Patent Foramen Ovale.

    PubMed

    Seo, Won-Woo; Kim, Sung Eun; Park, Myung-Soo; Lee, Jun-Hee; Park, Dae-Gyun; Han, Kyoo-Rok; Oh, Dong-Jin

    2017-09-01

    Trapped thrombus in patent foramen ovale (PFO) is a rare complication of pulmonary embolism that may lead to tragic clinical events. The aim of this study was to identify the optimal treatment for different clinical situations in patients with trapped thrombus in a PFO by conducting a literature review. A PubMed database search was conducted from 1991 through 2015, and 194 patients (185 articles) with trapped thrombus in a PFO were identified. Patient characteristics, paradoxical embolic events, and factors affecting 60-day mortality were analyzed retrospectively. Among all patients, 112 (57.7%) were treated with surgery, 28 with thrombolysis, and 54 with anticoagulation alone. Dyspnea (79.4%), chest pain (33.0%), and syncope (17.5%) were the most common presenting symptoms. Pretreatment embolism was found in 37.6% of cases, and stroke (24.7%) was the most common event. Surgery was associated with fewer post-treatment embolic events than were other treatment options (p=0.044). In the multivariate analysis, initial shock or arrest, and thrombolysis were independent predictors of 60-day mortality. Thrombolysis was related with higher 60-day mortality compared with surgery in patients who had no initial shock or arrest. This systematic review showed that surgery was associated with a lower overall incidence of post-treatment embolic events and a lower 60-day mortality in patients with trapped thrombus in a PFO. In patients without initial shock or arrest, thrombolysis was related with a higher 60-day mortality compared with surgery.

  9. Identification of intraluminal thrombus by ultrasonography in emergency department patients with acute deep venous thrombosis.

    PubMed

    Mehta, Ninfa; Schecter, Joshua; Stone, Michael

    2012-05-01

    Traditionally, the diagnosis of deep venous thrombosis (DVT) using duplex ultrasonography (DU) has relied on the absence of venous compressibility. Visualization of an intraluminal thrombus is considered an uncommon finding. The purpose of this study is to determine the frequency of intraluminal thrombus in emergency department (ED) patients diagnosed with acute DVT. Retrospective chart review of adult ED patients with DU examinations demonstrating acute DVT. Patients with chronic DVT or patients in whom DU did not demonstrate DVT were excluded from data analysis. Study reports and ultrasound images were reviewed and analyzed for the presence of intraluminal thrombus. There were 189 patients who met inclusion criteria, of which 160 (85%) were found to have intraluminal thrombus. Intraluminal thrombi are present in the majority of patients in our ED in whom acute DVT is identified by DU. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Correlation of Acute M1 Middle Cerebral Artery Thrombus Location with Endovascular Treatment Success and Clinical Outcome.

    PubMed

    Pavabvash, Seyedmehdi; Taleb, Shayandokht; Majidi, Shahram; Qureshi, Adnan I

    2017-01-01

    The location of the arterial occlusion can help with prognostication and treatment triage of acute stroke patients. We aimed to determine the effects of M1 distance-to-thrombus on angiographic recanalization success rate and clinical outcome following endovascular treatment of acute M1 occlusion. All acute ischemic stroke patients with M1 segment middle cerebral artery (MCA) occlusion on admission CT angiography (CTA) who underwent endovascular treatment were analyzed. The distance between thrombus origin and internal carotid artery (ICA) bifurcation was measured on admission CTA. The modified thrombolysis in cerebral infarction (mTICI) grades 2 b (>50% of distal branch filling) and 3 (complete) were considered as successful recanalization. Favorable outcome was defined by 3-month follow-up modified Rankin scale (mRs) score ≤2. Successful recanalization was achieved in 24 (71%) of 34 consecutive patients included in this study. The M1 distance-to-thrombus was shorter among patients with successful recanalization (5.4 ± 5.4 mm) versus those without (11.3 ± 7.6 mm, p = 0.015). The successful recanalization rate was higher among patients with M1 distance-to-thrombus ≤6 mm (odds ratio: 8, 95% confidence interval: 1.37-46.81, p = 0.023) compared with those with distance-to-thrombus >6 mm. There was no significant correlation between M1 distance-to-thrombus and 3-month mRs (rho: 0.131, p = 0.461); however, the distance-to-thrombus negatively correlated with admission National Institutes of Health Stroke Scale (NIHSS) scores (rho: -0.350, p=0.043). On the other hand, successful recanalization and admission NIHSS score were the only independent predictors of favorable outcome. Shorter distance of M1 thrombus from ICA bifurcation is associated with higher rate of successful recanalization following endovascular treatment.

  11. Correlation of Acute M1 Middle Cerebral Artery Thrombus Location with Endovascular Treatment Success and Clinical Outcome

    PubMed Central

    Pavabvash, Seyedmehdi; Taleb, Shayandokht; Majidi, Shahram; Qureshi, Adnan I.

    2017-01-01

    Purpose The location of the arterial occlusion can help with prognostication and treatment triage of acute stroke patients. We aimed to determine the effects of M1 distance-to-thrombus on angiographic recanalization success rate and clinical outcome following endovascular treatment of acute M1 occlusion. Methods All acute ischemic stroke patients with M1 segment middle cerebral artery (MCA) occlusion on admission CT angiography (CTA) who underwent endovascular treatment were analyzed. The distance between thrombus origin and internal carotid artery (ICA) bifurcation was measured on admission CTA. The modified thrombolysis in cerebral infarction (mTICI) grades 2b (>50% of distal branch filling) and 3 (complete) were considered as successful recanalization. Favorable outcome was defined by 3-month follow-up modified Rankin scale (mRs) score ≤2. Results Successful recanalization was achieved in 24 (71%) of 34 consecutive patients included in this study. The M1 distance-to-thrombus was shorter among patients with successful recanalization (5.4 ± 5.4 mm) versus those without (11.3 ± 7.6 mm, p = 0.015). The successful recanalization rate was higher among patients with M1 distance-to-thrombus ≤6 mm (odds ratio: 8, 95% confidence interval: 1.37–46.81, p = 0.023) compared with those with distance-to-thrombus >6 mm. There was no significant correlation between M1 distance-to-thrombus and 3-month mRs (rho: 0.131, p = 0.461); however, the distance-to-thrombus negatively correlated with admission National Institutes of Health Stroke Scale (NIHSS) scores (rho: −0.350, p=0.043). On the other hand, successful recanalization and admission NIHSS score were the only independent predictors of favorable outcome. Conclusion Shorter distance of M1 thrombus from ICA bifurcation is associated with higher rate of successful recanalization following endovascular treatment. PMID:28243346

  12. The free-radical scavenger edaravone accelerates thrombolysis with alteplase in an experimental thrombosis model.

    PubMed

    Yamashita, Tsutomu; Sato, Takumi; Sakamoto, Kumi; Ishii, Hiromitsu; Yamamoto, Junichiro

    2015-06-01

    Reperfusion injury after thrombolytic therapy can have adverse neurologic effects. The free-radical scavenger edaravone is used in combination with the recombinant tissue plasminogen activator alteplase to treat acute ischemic stroke. However, basic investigations of this combination use remain inadequate. Here, we used an in vivo model to investigate the effects of edaravone on alteplase-induced thrombolysis. Thrombolysis was evaluated by using a He-Ne-laser-induced thrombosis model in rat mesenteric microvessels. Changes in thrombus volume were analyzed with the image analysis software Image-Pro Plus (Media Cybernetics, USA). There were three experimental groups (placebo, alteplase 0.6 mg/kg, alteplase 0.6 mg/kg + edaravone 10.5 mg/kg). Sequential changes (0 to 60 min) in thrombus volume were compared by using a relative optical density method that we had used previously. In the placebo group, the thrombus volume at 60 min, reflecting the extent of thrombolysis, was 97.2% ± 5.7% of the initial value. In the alteplase group, thrombus volume decreased to 70.7% ± 4.1% (P<0.01) after 20 min and 14.2% ± 6.6% after 60 min. In the alteplase+edaravone group, thrombus volume decreased to 66.9% ± 7.2% (P<0.001) after 10 min and 10.9% ± 2.3% after 60 min. These results support the hypothesis that edaravone accelerates thrombolysis by alteplase. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Extensive Mobile Thrombus of the Internal Carotid Discovered After Intravenous Thrombolysis

    PubMed Central

    Fugate, Jennifer E.; Hocker, Sara E.

    2016-01-01

    This case report describes a rare presentation of ischemic stroke secondary to an extensive internal carotid artery thrombus, subsequent therapeutic dilemma, and clinical management. A 58-year-old man was administered intravenous (IV) thrombolysis for right middle cerebral artery territory ischemic stroke symptoms. A computed tomography angiogram of the head and neck following thrombolysis showed a longitudinally extensive internal carotid artery thrombus originating at the region of high-grade calcific stenosis. Mechanical embolectomy was deferred because of risk of clot dislodgement and mild neurological symptoms. Recumbency and hemodynamic augmentation were used acutely to support cerebral perfusion. Anticoagulation was started 24 hours after thrombolysis. Carotid endarterectomy was completed successfully within 1 week of presentation. Clinical outcome was satisfactory with discharge modified Rankin Scale score 0. A longitudinally extensive carotid artery thrombus poses a risk of dislodgement and hemispheric stroke. Optimal management in these cases is not known with certainty. In our case, IV thrombolysis, hemodynamic augmentation, delayed anticoagulation, and carotid endarterectomy resulted in a favorable clinical outcome. PMID:28400904

  14. Bacterial signatures in thrombus aspirates of patients with lower limb arterial and venous thrombosis.

    PubMed

    Vakhitov, Damir; Tuomisto, Sari; Martiskainen, Mika; Korhonen, Janne; Pessi, Tanja; Salenius, Juha-Pekka; Suominen, Velipekka; Lehtimäki, Terho; Karhunen, Pekka J; Oksala, Niku

    2018-06-01

    Increasing data supports the role of bacterial inflammation in adverse events of cardiovascular and cerebrovascular diseases. In our previous research, DNA of bacterial species found in coronary artery thrombus aspirates and ruptured cerebral aneurysms were mostly of endodontic and periodontal origin, where Streptococcus mitis group DNA was the most common. We hypothesized that the genomes of S mitis group could be identified in thrombus aspirates of patients with lower limb arterial and deep venous thrombosis. Thrombus aspirates and control blood samples taken from 42 patients with acute or acute-on-chronic lower limb ischemia (Rutherford I-IIb) owing to arterial or graft thrombosis (n = 31) or lower limb deep venous thrombosis (n = 11) were examined using a quantitative real-time polymerase chain reaction to detect all possible bacterial DNA and DNA of S mitis group in particular. The samples were considered positive, if the amount of bacterial DNA in the thrombus aspirates was 2-fold or greater in comparison with control blood samples. In the positive samples the mean difference for the total bacterial DNA was 12.1-fold (median, 7.1), whereas the differences for S mitis group DNA were a mean of 29.1 and a median of 5.2-fold. Of the arterial thrombus aspirates, 57.9% were positive for bacterial DNA, whereas bacterial genomes were found in 75% of bypass graft thrombosis with 77.8% of the prosthetic grafts being positive. Of the deep vein thrombus aspirates, 45.5% contained bacterial genomes. Most (80%) of bacterial DNA-positive cases contained DNA from the S mitis group. Previous arterial interventions were significantly associated with the occurrence of S mitis group DNA (P = .049, Fisher's exact test). This is the first study to report the presence of bacterial DNA, predominantly of S mitis group origin, in the thrombus aspirates of surgical patients with lower limb arterial and deep venous thrombosis, suggesting their possible role in the pathogenesis of

  15. In vivo magnetization transfer and diffusion-weighted magnetic resonance imaging detects thrombus composition in a mouse model of deep vein thrombosis.

    PubMed

    Phinikaridou, Alkystis; Andia, Marcelo E; Saha, Prakash; Modarai, Bijan; Smith, Alberto; Botnar, René M

    2013-05-01

    Deep vein thrombosis remains a major health problem necessitating accurate diagnosis. Thrombolysis is associated with significant morbidity and is effective only for the treatment of unorganized thrombus. We tested the feasibility of in vivo magnetization transfer (MT) and diffusion-weighted magnetic resonance imaging to detect thrombus organization in a murine model of deep vein thrombosis. Deep vein thrombosis was induced in the inferior vena cava of male BALB/C mice. Magnetic resonance imaging was performed at days 1, 7, 14, 21, and 28 after thrombus induction using MT, diffusion-weighted, inversion-recovery, and T1-mapping protocols. Delayed enhancement and T1 mapping were repeated 2 hours after injection of a fibrin contrast agent. Finally, excised thrombi were used for histology. We found that MT and diffusion-weighted imaging can detect histological changes associated with thrombus aging. MT rate (MTR) maps and percentage of MT rate (%MTR) allowed visualization and quantification of the thrombus protein content, respectively. The %MTR increased with thrombus organization and was significantly higher at days 14, 21, and 28 after thrombus induction (days 1, 7, 14, 21, 28: %MTR=2483±451, 2079±1210, 7029±2490, 10 295±4356, 32 994±25 449; PANOVA<0.05). There was a significant positive correlation between the %MTR and the histological protein content of the thrombus (r=0.70; P<0.05). The apparent diffusion coefficient was lower in erythrocyte-rich and collagen-rich thrombus (0.72±0.10 and 0.69±0.05 [×10(-3) mm(2)/s]). Thrombus at days 7 and 14 had the highest apparent diffusion coefficient values (0.95±0.09 and 1.10±0.18 [×10(-3) mm(2)/s]). MT and diffusion-weighted magnetic resonance imaging sequences are promising for the staging of thrombus composition and could be useful in guiding medical intervention.

  16. Impact of thrombus length on recanalization and clinical outcome following mechanical thrombectomy in acute ischemic stroke.

    PubMed

    Seker, Fatih; Pfaff, Johannes; Wolf, Marcel; Schönenberger, Silvia; Nagel, Simon; Herweh, Christian; Pham, Mirko; Bendszus, Martin; Möhlenbruch, Markus A

    2017-10-01

    The impact of thrombus length on recanalization in IV thrombolysis for acute intracranial artery occlusion has been well studied. Here we analyzed the influence of thrombus length on the number of thrombectomy maneuvers needed for recanalization, intraprocedural complications, recanalization success, and clinical outcome after mechanical thrombectomy. We retrospectively analyzed angiographic and clinical data from 72 consecutive patients with acute occlusion of the M1 segment of the middle cerebral artery who were treated with mechanical thrombectomy using stent retrievers. Successful recanalization was defined as a Thrombolysis in Cerebral Infarction score of 2b or 3. Good neurological outcome was defined as a modified Rankin Scale score of ≤2 at 90 days after stroke onset. Mean thrombus length was 13.4±5.2 mm. Univariate binary logistic regression did not show an association of thrombus length with the probability of a good clinical outcome (OR 0.95, 95% CI 0.84 to 1.03, p=0.176) or successful recanalization (OR 0.92, 95% CI 0.81 to 1.05, p=0.225). There was no significant correlation between thrombus length and the number of thrombectomy maneuvers needed for recanalization (p=0.112). Furthermore, thrombus length was not correlated with the probability of intraprocedural complications (p=0.813), including embolization in a new territory (n=3). In this study, thrombus length had no relevant impact on recanalization, neurological outcome, or intraprocedural complications following mechanical thrombectomy of middle cerebral artery occlusions. Therefore, mechanical thrombectomy with stent retrievers can be attempted with large clots. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  17. Vortex Formation and Acceleration of a Fish-Inspired Robot Performing Starts from Rest

    NASA Astrophysics Data System (ADS)

    Devoria, Adam; Bapst, Jonathan; Ringuette, Matthew

    2009-11-01

    We investigate the unsteady flow of a fish-inspired robot executing starts from rest, with the objective of understanding the connection among the kinematics, vortex formation, and acceleration performance. Several fish perform ``fast starts,'' where the body bends into a ``C'' or ``S'' shape while turning (phase I), followed by a straightening of the body and caudal fin and a linear acceleration (phase II). The resulting highly 3-D, unsteady vortex formation and its relationship to the acceleration are not well understood. The self-propelled robotic model contains motor-driven joints with programmable motion to emulate phase II of a simplified C-start. The experiments are conducted in a water tank, and the model is constrained to 1 direction along rails. The velocity is measured using digital particle image velocimetry (DPIV) in multiple planes. Vortex boundaries are identified using the finite-time Lyapunov exponent, then the unsteady vortex circulation is computed. The thrust is estimated from the identified vortices, and correlated with the circulation and model acceleration for different kinematics.

  18. Artificial aortic valve dysfunction due to pannus and thrombus - different methods of cardiac surgical management.

    PubMed

    Ostrowski, Stanisław; Marcinkiewicz, Anna; Kośmider, Anna; Walczak, Andrzej; Zwoliński, Radosław; Jaszewski, Ryszard

    2015-09-01

    Approximately 60 000 prosthetic valves are implanted annually in the USA. The risk of prosthesis dysfunction ranges from 0.1% to 4% per year. Prosthesis valve dysfunction is usually caused by a thrombus obstructing the prosthetic discs. However, 10% of prosthetic valves are dysfunctional due to pannus formation, and 12% of prostheses are damaged by both fibrinous and thrombotic components. The authors present two patients with dysfunctional aortic prostheses who were referred for cardiac surgery. Different surgical solutions were used in the treatment of each case. The first patient was a 71-year-old woman whose medical history included arterial hypertension, stable coronary artery disease, diabetes mellitus, chronic obstructive pulmonary disease (COPD), and hypercholesterolemia; she had previously undergone left-sided mastectomy and radiotherapy. The patient was admitted to the Cardiac Surgery Department due to aortic prosthesis dysfunction. Transthoracic echocardiography revealed complete obstruction of one disc and a severe reduction in the mobility of the second. The mean transvalvular gradient was very high. During the operation, pannus covering the discs' surface was found. A biological aortic prosthesis was reimplanted without complications. The second patient was an 87-year-old woman with arterial hypertension, persistent atrial fibrillation, and COPD, whose past medical history included gastric ulcer disease and ischemic stroke. As in the case of the first patient, she was admitted due to valvular prosthesis dysfunction. Preoperative transthoracic echocardiography revealed an obstruction of the posterior prosthetic disc and significant aortic regurgitation. Transesophageal echocardiography and fluoroscopy confirmed the prosthetic dysfunction. During the operation, a thrombus growing around a minor pannus was found. The thrombus and pannus were removed, and normal functionality of the prosthetic valve was restored. Precise and modern diagnostic methods

  19. Collisionless shock formation and the prompt acceleration of solar flare ions

    NASA Technical Reports Server (NTRS)

    Cargill, P. J.; Goodrich, C. C.; Vlahos, L.

    1988-01-01

    The formation mechanisms of collisionless shocks in solar flare plasmas are investigated. The priamry flare energy release is assumed to arise in the coronal portion of a flare loop as many small regions or 'hot spots' where the plasma beta locally exceeds unity. One dimensional hybrid numerical simulations show that the expansion of these 'hot spots' in a direction either perpendicular or oblique to the ambient magnetic field gives rise to collisionless shocks in a few Omega(i), where Omega(i) is the local ion cyclotron frequency. For solar parameters, this is less than 1 second. The local shocks are then subsequently able to accelerate particles to 10 MeV in less than 1 second by a combined drift-diffusive process. The formation mechanism may also give rise to energetic ions of 100 keV in the shock vicinity. The presence of these energetic ions is due either to ion heating or ion beam instabilities and they may act as a seed population for further acceleration. The prompt acceleration of ions inferred from the Gamma Ray Spectrometer on the Solar Maximum Mission can thus be explained by this mechanism.

  20. Accelerated formation of cubic phases in phosphatidylethanolamine dispersions.

    PubMed Central

    Tenchov, B; Koynova, R; Rapp, G

    1998-01-01

    By means of x-ray diffraction we show that several sodium salts and the disaccharides sucrose and trehalose strongly accelerate the formation of cubic phases in phosphatidylethanolamine (PE) dispersions upon temperature cycling through the lamellar liquid crystalline-inverted hexagonal (Lalpha-HII) phase transition. Ethylene glycol does not have such an effect. The degree of acceleration increases with the solute concentration. Such an acceleration has been observed for dielaidoyl PE (DEPE), dihexadecyl PE, and dipalmitoyl PE. It was investigated in detail for DEPE dispersions. For DEPE (10 wt% of lipid) aqueous dispersions at 1 M solute concentration, 10-50 temperature cycles typically result in complete conversion of the Lalpha phase into cubic phase. Most efficient is temperature cycling executed by laser flash T-jumps. In that case the conversion completes within 10-15 cycles. However, the cubic phases produced by laser T-jumps are less ordered in comparison to the rather regular cubic structures produced by linear, uniform temperature cycling at 10 degrees C/min. Temperature cycles at scan rates of 1-3 degrees C/min also induce the rapid formation of cubic phases. All solutes used induce the formation of Im3m (Q229) cubic phase in 10 wt% DEPE dispersions. The initial Im3m phases appearing during the first temperature cycles have larger lattice parameters that relax to smaller values with continuation of the cycling after the disappearance of the Lalpha phase. A cooperative Im3m --> Pn3m transition takes place at approximately 85 degrees C and transforms the Im3m phase into a mixture of coexisting Pn3m (Q224) and Im3m phases. The Im3m/Pn3m lattice parameter ratio is 1. 28, as could be expected from a representation of the Im3m and Pn3m phases with the primitive and diamond infinite periodic minimal surfaces, respectively. At higher DEPE contents ( approximately 30 wt%), cubic phase formation is hindered after 20-30 temperature cycles. The conversion does not go

  1. Enhanced levels of soluble CD40 ligand exacerbate platelet aggregation and thrombus formation through a CD40-dependent tumor necrosis factor receptor-associated factor-2/Rac1/p38 mitogen-activated protein kinase signaling pathway.

    PubMed

    Yacoub, Daniel; Hachem, Ahmed; Théorêt, Jean-François; Gillis, Marc-Antoine; Mourad, Walid; Merhi, Yahye

    2010-12-01

    CD40 ligand is a thromboinflammatory molecule that predicts cardiovascular events. Platelets constitute the major source of soluble CD40 ligand (sCD40L), which has been shown to influence platelet activation, although its exact functional impact on platelets and the underlying mechanisms remain undefined. We aimed to determine the impact and the signaling mechanisms of sCD40L on platelets. sCD40L strongly enhances platelet activation and aggregation. Human platelets treated with a mutated form of sCD40L that does not bind CD40, and CD40(-/-) mouse platelets failed to elicit such responses. Furthermore, sCD40L stimulation induces the association of the tumor necrosis factor receptor-associated factor-2 with platelet CD40. Notably, sCD40L primes platelets through activation of the small GTPase Rac1 and its downstream target p38 mitogen-activated protein kinase, which leads to platelet shape change and actin polymerization. Moreover, sCD40L exacerbates thrombus formation and leukocyte infiltration in wild-type mice but not in CD40(-/-) mice. sCD40L enhances agonist-induced platelet activation and aggregation through a CD40-dependent tumor necrosis factor receptor-associated factor-2/Rac1/p38 mitogen-activated protein kinase signaling pathway. Thus, sCD40L is an important platelet primer predisposing platelets to enhanced thrombus formation in response to vascular injury. This may explain the link between circulating levels of sCD40L and cardiovascular diseases.

  2. 3D Resistive MHD Simulations of Formation, Compression, and Acceleration of Compact Tori

    NASA Astrophysics Data System (ADS)

    Woodruff, Simon; Meyer, Thomas; Stuber, James; Romero-Talamas, Carlos; Brown, Michael; Kaur, Manjit; Schaffner, David

    2017-10-01

    We present results from extended resistive 3D MHD simulations (NIMROD) pertaining to a new formation method for toroidal plasmas using a reconnection region that forms in a radial implosion, and results from the acceleration of CTs along a drift tube that are accelerated by a coil and are allowed to go tilt unstable and form a helical minimum energy state. The new formation method results from a reconnection region that is generated between two magnetic compression coils that are ramped to 320kV in 2 μs. When the compressing field is aligned anti-parallel to a pre-existing CT, a current sheet and reconnection region forms that accelerates plasma radially inwards up to 500km/s which stagnates and directed energy converts to thermal, raising temperatures to 500eV. When field is aligned parallel to the pre-existing CT, the configuration can be accelerated along a drift tube. For certain ratios of magnetic field to density, the CT goes tilt-unstable forming a twisted flux rope, which can also be accelerated and stagnated on an end wall, where temperature and field increases as the plasma compresses. We compare simulation results with adiabatic scaling relations. Work supported by ARPA-E ALPHA program and DARPA.

  3. Ginsenoside-Rp3 inhibits platelet activation and thrombus formation by regulating MAPK and cyclic nucleotide signaling.

    PubMed

    Irfan, Muhammad; Jeong, Da Hye; Kwon, Hyuk-Woo; Shin, Jung-Hae; Park, Sang-Joon; Kwak, Dongmi; Kim, Tae-Hwan; Lee, Dong-Ha; Park, Hwa-Jin; Rhee, Man Hee

    2018-06-08

    Ginseng (Panax ginseng C.A. Mayer) contains saponin fractions called ginsenosides, which are thought to be the main components responsible for its various pharmacological activities. Ginsenosides have cardioprotective and antiplatelet effects. In the present study, we evaluated the effects of ginsenoside Rp3 (G-Rp3) on platelet function. The in vitro effects of G-Rp3 were evaluated on agonist-induced human and rat platelet aggregation, while [Ca 2+ ] i mobilization, granule secretion, integrin α IIb β 3 activation, and clot retraction were assessed in rat platelets. Its effects on vasodilator-stimulated phosphoprotein (VASP) expression, phosphorylation of MAPK signaling molecules, and PI3K/Akt activation were also studied. Moreover, the tyrosine phosphorylation of components of the P 2 Y 12 receptor downstream signaling pathway was also examined. The in vivo effects of G-Rp3 were studied using an acute pulmonary thromboembolism model and lung histopathology. G-Rp3 significantly inhibited collagen, ADP, and thrombin-induced platelet aggregation. G-Rp3 elevated cAMP levels and VASP phosphorylation and suppressed agonist-induced [Ca 2+ ] i mobilization, ATP release, and P-selectin expression along with fibrinogen binding to integrin α IIb β 3 , fibronectin adhesion, and clot retraction. G-Rp3 also attenuated the phosphorylation of MAPK, Src, and PLCγ2 as well as PI3K/Akt activation. Furthermore, it inhibited tyrosine phosphorylation of the Src family kinases (Src, Fyn, and Lyn) and PLCγ2 and protected mice from thrombosis. G-Rp3 modulates agonist-induced platelet activation and thrombus formation by inhibiting granule secretion, integrin α IIb β 3 activation, MAPK signaling, and Src, PLCγ2, and PI3K/Akt activation, and VASP stimulation. Our data suggest that G-Rp3 has therapeutic potential as a treatment for platelet-related cardiovascular disorders. Copyright © 2017. Published by Elsevier Inc.

  4. In Vivo Magnetization Transfer and Diffusion-Weighted Magnetic Resonance Imaging Detects Thrombus Composition in a Mouse Model of Deep Vein Thrombosis

    PubMed Central

    Saha, Prakash; Modarai, Bijan; Smith, Alberto; Botnar, René M.

    2014-01-01

    Background Deep vein thrombosis remains a major health problem necessitating accurate diagnosis. Thrombolysis is associated with significant morbidity and is effective only for the treatment of unorganized thrombus. We tested the feasibility of in vivo magnetization transfer (MT) and diffusion-weighted magnetic resonance imaging to detect thrombus organization in a murine model of deep vein thrombosis. Methods and Results Deep vein thrombosis was induced in the inferior vena cava of male BALB/C mice. Magnetic resonance imaging was performed at days 1, 7, 14, 21, and 28 after thrombus induction using MT, diffusion-weighted, inversion-recovery, and T1-mapping protocols. Delayed enhancement and T1 mapping were repeated 2 hours after injection of a fibrin contrast agent. Finally, excised thrombi were used for histology. We found that MT and diffusion-weighted imaging can detect histological changes associated with thrombus aging. MT rate (MTR) maps and percentage of MT rate (%MTR) allowed visualization and quantification of the thrombus protein content, respectively. The %MTR increased with thrombus organization and was significantly higher at days 14, 21, and 28 after thrombus induction (days 1, 7, 14, 21, 28: %MTR=2483±451, 2079±1210, 7029±2490, 10 295±4356, 32 994±25 449; Panova<0.05). There was a significant positive correlation between the %MTR and the histological protein content of the thrombus (r=0.70; P<0.05). The apparent diffusion coefficient was lower in erythrocyte-rich and collagen-rich thrombus (0.72±0.10 and 0.69±0.05 [×10−3 mm2/s]). Thrombus at days 7 and 14 had the highest apparent diffusion coefficient values (0.95±0.09 and 1.10±0.18 [×10−3 mm2/s]). Conclusions MT and diffusion-weighted magnetic resonance imaging sequences are promising for the staging of thrombus composition and could be useful in guiding medical intervention. PMID:23564561

  5. Immunohistochemical detection of intrathrombotic fibrocytes and its application to thrombus age estimation in murine deep vein thrombosis model.

    PubMed

    Nosaka, Mizuho; Ishida, Yuko; Kimura, Akihiko; Kawaguchi, Takashi; Yamamoto, Hiroki; Kuninaka, Yumi; Kondo, Toshikazu

    2017-01-01

    Deep vein thrombi are dissolved after fibrosis process along with an increase of thrombus age. Fibrocytes are circulating bone marrow-derived cells with mesenchymal features that potentially have a unique and critical function in fibrosis. In this study, a double-color immunofluorescence analysis was carried out by using anti-CD45 and anti-collagen type I antibodies to examine the time-dependent appearance of fibrocytes in the murine model of stasis-induced deep vein thrombosis. The thrombus ages were 1, 3, 5, 7, 10, 14, and 21 days. In a thrombus age of less than 5 days, CD45 + and collagen type I + fibrocytes were never detected. The intrathrombotic fibrocytes were initially observed in thrombi aged 7 days, and their number increased with advances in thrombus age. In a quantitative morphometrical analysis, the average number of intrathrombotic fibrocytes was highest in 14-day-old thrombi, and all of the five samples aged 14 days had the fibrocyte number of more than 25, and in three out of them, the number of intrathrombotic fibrocytes was over 30. On the contrary, in all of thrombus samples with the postligation intervals of 10 and 21 days, the number of intrathrombotic fibrocytes was less than 25. These observations imply that thrombi containing fibrocytes are at least 7 days old and that a fibrocyte number exceeding 30 would indicate the thrombus age of approximately 14 days. Our observations indicate that the detection of fibrocytes could be useful for thrombus age determination.

  6. The electrolytic inferior vena cava model (EIM) to study thrombogenesis and thrombus resolution with continuous blood flow in the mouse

    PubMed Central

    Diaz, Jose A.; Alvarado, Christine M.; Wrobleski, Shirley K.; Slack, Dallas W.; Hawley, Angela E.; Farris, Diana M.; Henke, Peter K.; Wakefield, Thomas W.; Myers, Daniel D.

    2016-01-01

    Summary Previously, we presented the electrolytic inferior vena cava (IVC) model (EIM) during acute venous thrombosis (VT). Here, we present our evaluation of the EIM for chronic VT time points in order to determine whether this model allows for the study of thrombus resolution. C57BU6 mice (n=191) were utilised. In this model a copper-wire, inserted into a 25-gauge needle, is placed in the distal IVC and another subcutaneously. An electrical current (250 µAmp/15 minutes) activates the endothelial cells, inducing thrombogenesis. Ultrasound, thrombus weight (TW), vein wall leukocyte counts, vein wall thickness/fibrosis scoring, thrombus area and soluble P-selectin (sP-sel) were performed at baseline, days 1, 2, 4, 6, 9, 11 and 14, post EIM. A correlation between TW and sP-sel was also determined. A thrombus formed in each mouse undergoing EIM. Blood flow was documented by ultrasound at all time points. IVC thrombus size increased up to day 2 and then decreased over time, as shown by ultrasound, TW, and sP-sel levels. TW and sP-sel showed a strong positive correlation (r=0.48, p<0.0002). Vein wall neutrophils were the most common cell type present in acute VT (up to day 2) with monocytes becoming the most prevalent in chronic VT (from day 6 to day 14). Thrombus resolution was demonstrated by ultrasound, TW and thrombus area. In conclusion, the EIM produces a non-occlusive and consistent IVC thrombus, in the presence of constant blood flow, allowing for the study of VT at both acute and chronic time points. Thrombus resolution was demonstrated by all modalities utilised in this study. PMID:23571406

  7. Prevention of Left Ventricular Thrombus Formation and Systemic Embolism After Anterior Myocardial Infarction: A Systematic Literature Review.

    PubMed

    Bastiany, Alexandra; Grenier, Marie-Eve; Matteau, Alexis; Mansour, Samer; Daneault, Benoit; Potter, Brian J

    2017-10-01

    Anterior myocardial infarction (MI) with apical dysfunction is associated with an increased risk of left ventricular thrombus (LVT) formation and systemic embolism (SE). However, the role for prophylactic anticoagulation in current practice is a matter of debate. We conducted a systematic review of peer-reviewed original articles in either English or French on the benefit of combining anticoagulation with standard therapy for the prevention of LVT/SE after MI by searching PubMed, Ovid/MedLine/Embase, the Cochrane Library, and Google Scholar. Of 7382 identified records, 14 were retained for analysis. Nine articles addressed anticoagulation for patients not treated with percutaneous coronary intervention (PCI). Another 5 included at least some patients treated with PCI. Only 1 study specifically addressed exclusively a primary PCI population. Some studies showed a benefit for combining anticoagulation with standard therapy in patients not treated with PCI, but results were inconsistent. No evidence of benefit was reported when PCI patients were included and 1 study reported a signal for net harm. There was important interstudy heterogeneity and methodological limitations. Studies were likely individually underpowered. The available studies of LVT/SE prevention after MI lacked statistical power and are heterogeneous in terms of treatments, revascularization methods, background medical therapy, and study design. We conclude that there is presently no compelling evidence for or against combining anticoagulation with standard therapy for post-MI patients with apical dysfunction after primary PCI, and inconsistent evidence supporting prophylaxis after thrombolysis. An appropriately powered randomized trial is required to answer this clinically relevant question. Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  8. Innate Effector-Memory T-Cell Activation Regulates Post-Thrombotic Vein Wall Inflammation and Thrombus Resolution.

    PubMed

    Luther, Natascha; Shahneh, Fatemeh; Brähler, Melanie; Krebs, Franziska; Jäckel, Sven; Subramaniam, Saravanan; Stanger, Christian; Schönfelder, Tanja; Kleis-Fischer, Bettina; Reinhardt, Christoph; Probst, Hans Christian; Wenzel, Philip; Schäfer, Katrin; Becker, Christian

    2016-12-09

    Immune cells play an important role during the generation and resolution of thrombosis. T cells are powerful regulators of immune and nonimmune cell function, however, their role in sterile inflammation in venous thrombosis has not been systematically examined. This study investigated the recruitment, activation, and inflammatory activity of T cells in deep vein thrombosis and its consequences for venous thrombus resolution. CD4 + and CD8 + T cells infiltrate the thrombus and vein wall rapidly on deep vein thrombosis induction and remain in the tissue throughout the thrombus resolution. In the vein wall, recruited T cells largely consist of effector-memory T (T EM ) cells. Using T-cell receptor transgenic reporter mice, we demonstrate that deep vein thrombosis-recruited T EM receive an immediate antigen-independent activation and produce IFN-γ (interferon) in situ. Mapping inflammatory conditions in the thrombotic vein, we identify a set of deep vein thrombosis upregulated cytokines and chemokines that synergize to induce antigen-independent IFN-γ production in CD4 + and CD8 + T EM cells. Reducing the number of T EM cells through a depletion recovery procedure, we show that intravenous T EM activation determines neutrophil and monocyte recruitment and delays thrombus neovascularization and resolution. Examining T-cell recruitment in human venous stasis, we show that superficial varicose veins preferentially contain activated memory T cells. T EM orchestrate the inflammatory response in venous thrombosis affecting thrombus resolution. © 2016 American Heart Association, Inc.

  9. Simultaneous bright‐ and black‐blood whole‐heart MRI for noncontrast enhanced coronary lumen and thrombus visualization

    PubMed Central

    Neji, Radhouene; Phinikaridou, Alkystis; Whitaker, John; Botnar, René M.; Prieto, Claudia

    2017-01-01

    Purpose To develop a 3D whole‐heart Bright‐blood and black‐blOOd phase SensiTive (BOOST) inversion recovery sequence for simultaneous noncontrast enhanced coronary lumen and thrombus/hemorrhage visualization. Methods The proposed sequence alternates the acquisition of two bright‐blood datasets preceded by different preparatory pulses to obtain variations in blood/myocardium contrast, which then are combined in a phase‐sensitive inversion recovery (PSIR)‐like reconstruction to obtain a third, coregistered, black‐blood dataset. The bright‐blood datasets are used for both visualization of the coronary lumen and motion estimation, whereas the complementary black‐blood dataset potentially allows for thrombus/hemorrhage visualization. Furthermore, integration with 2D image‐based navigation enables 100% scan efficiency and predictable scan times. The proposed sequence was compared to conventional coronary MR angiography (CMRA) and PSIR sequences in a standardized phantom and in healthy subjects. Feasibility for thrombus depiction was tested ex vivo. Results With BOOST, the coronary lumen is visualized with significantly higher (P < 0.05) contrast‐to‐noise ratio and vessel sharpness when compared to conventional CMRA. Furthermore, BOOST showed effective blood signal suppression as well as feasibility for thrombus visualization ex vivo. Conclusion A new PSIR sequence for noncontrast enhanced simultaneous coronary lumen and thrombus/hemorrhage detection was developed. The sequence provided improved coronary lumen depiction and showed potential for thrombus visualization. Magn Reson Med 79:1460–1472, 2018. © 2017 International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. PMID:28722267

  10. Multisite Thrombus Imaging and Fibrin Content Estimation With a Single Whole-Body PET Scan in Rats.

    PubMed

    Blasi, Francesco; Oliveira, Bruno L; Rietz, Tyson A; Rotile, Nicholas J; Naha, Pratap C; Cormode, David P; Izquierdo-Garcia, David; Catana, Ciprian; Caravan, Peter

    2015-10-01

    Thrombosis is a leading cause of morbidity and mortality worldwide. Current diagnostic strategies rely on imaging modalities that are specific for distinct vascular territories, but a thrombus-specific whole-body imaging approach is still missing. Moreover, imaging techniques to assess thrombus composition are underdeveloped, although therapeutic strategies may benefit from such technology. Therefore, our goal was to test whether positron emission tomography (PET) with the fibrin-binding probe (64)Cu-FBP8 allows multisite thrombus detection and fibrin content estimation. Thrombosis was induced in Sprague-Dawley rats (n=32) by ferric chloride application on both carotid artery and femoral vein. (64)Cu-FBP8-PET/CT imaging was performed 1, 3, or 7 days after thrombosis to detect thrombus location and to evaluate age-dependent changes in target uptake. Ex vivo biodistribution, autoradiography, and histopathology were performed to validate imaging results. Arterial and venous thrombi were localized on fused PET/CT images with high accuracy (97.6%; 95% confidence interval, 92-100). A single whole-body PET/MR imaging session was sufficient to reveal the location of both arterial and venous thrombi after (64)Cu-FBP8 administration. PET imaging showed that probe uptake was greater in younger clots than in older ones for both arterial and venous thrombosis (P<0.0001). Quantitative histopathology revealed an age-dependent reduction of thrombus fibrin content (P<0.001), consistent with PET results. Biodistribution and autoradiography further confirmed the imaging findings. We demonstrated that (64)Cu-FBP8-PET is a feasible approach for whole-body thrombus detection and that molecular imaging of fibrin can provide, noninvasively, insight into clot composition. © 2015 American Heart Association, Inc.

  11. Pulmonary embolism due to right ventricular thrombus in a case of Behcet's disease.

    PubMed

    Yasuo, M; Nagano, S; Yazaki, Y; Koizumi, T; Kitabayashi, H; Imamura, H; Amano, J; Isobe, M

    1999-11-01

    Right ventricular thrombus is a very rare manifestation of cardiovascular Behcet's disease. A 25-year-old man was admitted to hospital due to cough and fever of unknown origin. He experienced repetitive pulmonary embolism due to a right ventricular thrombus, which was surgically removed. A diagnosis of Behcet's disease was made based on his clinical course and the histological findings of the right ventricular wall and the skin lesion. He was quickly relieved of his symptoms after warfarinization and cyclosporine therapy.

  12. [Surgical Treatment of Right Atrial Malignant Tumor Thrombus Under Deep Hypothermia with Intermittent Circulatory Arrest;Report of Two Cases].

    PubMed

    Fujita, Akira; Kobayashi, Toshiro; Hironaka, Hideharu; Jinbou, Mitsutaka; Uesugi, Naomasa; Saito, Satoshi; Takahashi, Tsuyoshi; Gohra, Hidenori

    2016-12-01

    Right atrial tumor thrombus is rare in patients with visceral malignant tumors and can cause right heart failure or sudden death. We present 2 cases of right atrial tumor thrombus treated under deep hypothermic intermittent circulatory arrest (DHICA). A 45-year-old man with right heart failure was diagnosed with right renal cancer extending to the right atrium. Computed tomography revealed no metastasis. He underwent right nephrectomy and tumor thrombus resection under DHICA. He was discharged on postoperative day 11 in good clinical course. A 67-year-old woman with hepatitis C virus liver cirrhosis( Child-Pugh A) was diagnosed with hepatocellular carcinoma and right atrial tumor. She underwent S8 and tumor thrombus resection under DHICA. Hemorrhagic diathesis was controlled using fresh frozen plasma transfusion. She was discharged on postoperative day 24 without liver failure. In cases of atrial tumor thrombus resection, DIHCA may be useful to achieve a bloodless operation field because the procedure is relatively simple and the primary disease need not be considered.

  13. Thrombin-activatable fluorescent peptide incorporated gold nanoparticles for dual optical/computed tomography thrombus imaging.

    PubMed

    Kwon, Sung-Pil; Jeon, Sangmin; Lee, Sung-Hoon; Yoon, Hong Yeol; Ryu, Ju Hee; Choi, Dayil; Kim, Jeong-Yeon; Kim, Jiwon; Park, Jae Hyung; Kim, Dong-Eog; Kwon, Ick Chan; Kim, Kwangmeyung; Ahn, Cheol-Hee

    2018-01-01

    Thrombosis is an important pathophysiologic phenomenon in various cardiovascular diseases, which can lead to oxygen deprivation and infarction of tissues by generation of a thrombus. Thus, direct thrombus imaging can provide beneficial in diagnosis and therapy of thrombosis. Herein, we developed thrombin-activatable fluorescent peptide (TAP) incorporated silica-coated gold nanoparticles (TAP-SiO 2 @AuNPs) for direct imaging of thrombus by dual near-infrared fluorescence (NIRF) and micro-computed tomography (micro-CT) imaging, wherein TAP molecules were used as targeted thrombin-activatable peptide probes for thrombin-specific NIRF imaging. The freshly prepared TAP-SiO 2 @AuNPs had an average diameter of 39.8 ± 2.55 nm and they showed the quenched NIRF signal in aqueous condition, due to the excellent quenching effect of TAP molecules on the silica-gold nanoparticle surface. However, 30.31-fold higher NIRF intensity was rapidly recovered in the presence of thrombin in vitro, due to the thrombin-specific cleavage of quenched TAP molecules on the gold particle surface. Furthermore, TAP-SiO 2 @AuNPs were successfully accumulated in thrombus by their particle size-dependent capturing property, and they presented a potential X-ray absorption property in a dose-dependent manner. Finally, thrombotic lesion was clearly distinguished from peripheral tissues by dual NIRF/micro-CT imaging after intravenous injection of TAP-SiO 2 @AuNPs in the in situ thrombotic mouse model, simultaneously. This study showed that thrombin-activatable fluorescent peptide incorporated silica-coated gold nanoparticles can be potentially used as a dual imaging probe for direct thrombus imaging and therapy in clinical applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Artificial aortic valve dysfunction due to pannus and thrombus – different methods of cardiac surgical management

    PubMed Central

    Marcinkiewicz, Anna; Kośmider, Anna; Walczak, Andrzej; Zwoliński, Radosław; Jaszewski, Ryszard

    2015-01-01

    Introduction Approximately 60 000 prosthetic valves are implanted annually in the USA. The risk of prosthesis dysfunction ranges from 0.1% to 4% per year. Prosthesis valve dysfunction is usually caused by a thrombus obstructing the prosthetic discs. However, 10% of prosthetic valves are dysfunctional due to pannus formation, and 12% of prostheses are damaged by both fibrinous and thrombotic components. The authors present two patients with dysfunctional aortic prostheses who were referred for cardiac surgery. Different surgical solutions were used in the treatment of each case. Case study 1 The first patient was a 71-year-old woman whose medical history included arterial hypertension, stable coronary artery disease, diabetes mellitus, chronic obstructive pulmonary disease (COPD), and hypercholesterolemia; she had previously undergone left-sided mastectomy and radiotherapy. The patient was admitted to the Cardiac Surgery Department due to aortic prosthesis dysfunction. Transthoracic echocardiography revealed complete obstruction of one disc and a severe reduction in the mobility of the second. The mean transvalvular gradient was very high. During the operation, pannus covering the discs’ surface was found. A biological aortic prosthesis was reimplanted without complications. Case study 2 The second patient was an 87-year-old woman with arterial hypertension, persistent atrial fibrillation, and COPD, whose past medical history included gastric ulcer disease and ischemic stroke. As in the case of the first patient, she was admitted due to valvular prosthesis dysfunction. Preoperative transthoracic echocardiography revealed an obstruction of the posterior prosthetic disc and significant aortic regurgitation. Transesophageal echocardiography and fluoroscopy confirmed the prosthetic dysfunction. During the operation, a thrombus growing around a minor pannus was found. The thrombus and pannus were removed, and normal functionality of the prosthetic valve was restored

  15. Pulmonary Embolism and Intracardiac Type A Thrombus with an Unexpected Outcome.

    PubMed

    Português, João; Calvo, Lucy; Oliveira, Margarida; Pereira, Vítor Hugo; Guardado, Joana; Lourenço, Mário Rui; Azevedo, Olga; Ferreira, Francisco; Canário-Almeida, Filipa; Lourenço, António

    2017-01-01

    Detection of right heart thrombi (RHT) in the context of pulmonary thromboembolism (PE) is uncommon (4-18%) and increases the risk of mortality beyond the presence of PE alone. Type A thrombi are serpiginous and highly mobile and are thought to be originated from large veins and captured in-transit within the right heart. Optimal management of RHT is still uncertain. A 79-year-old woman, with a history of recent total hysterectomy with adnexectomy and a Wells procedure, presented to the emergency department following an episode of syncope. Computed tomography revealed bilateral PE and the presence of a right atrial thrombus. Transthoracic echocardiography demonstrated a free-floating type A thrombus in the right atrium, protruding into the right ventricle, and signs of pulmonary hypertension and right ventricle dysfunction. Considering the recent surgery and clinical stability, treatment with heparin alone was decided. Subsequent clinical improvement was observed and echocardiographic follow-up revealed complete thrombus dissolution and complete recovery of right ventricle function. Most authors recommend treatment of PE with RHT with thrombolysis or embolectomy followed by anticoagulation, although evidence is scarce. Individual risk of hemorrhage and operatory-related mortality should be taken into account when defining the treatment strategy especially when benefit is not firmly established.

  16. Pulmonary Embolism and Intracardiac Type A Thrombus with an Unexpected Outcome

    PubMed Central

    Calvo, Lucy; Oliveira, Margarida; Pereira, Vítor Hugo; Guardado, Joana; Lourenço, Mário Rui; Azevedo, Olga; Ferreira, Francisco; Canário-Almeida, Filipa; Lourenço, António

    2017-01-01

    Detection of right heart thrombi (RHT) in the context of pulmonary thromboembolism (PE) is uncommon (4–18%) and increases the risk of mortality beyond the presence of PE alone. Type A thrombi are serpiginous and highly mobile and are thought to be originated from large veins and captured in-transit within the right heart. Optimal management of RHT is still uncertain. A 79-year-old woman, with a history of recent total hysterectomy with adnexectomy and a Wells procedure, presented to the emergency department following an episode of syncope. Computed tomography revealed bilateral PE and the presence of a right atrial thrombus. Transthoracic echocardiography demonstrated a free-floating type A thrombus in the right atrium, protruding into the right ventricle, and signs of pulmonary hypertension and right ventricle dysfunction. Considering the recent surgery and clinical stability, treatment with heparin alone was decided. Subsequent clinical improvement was observed and echocardiographic follow-up revealed complete thrombus dissolution and complete recovery of right ventricle function. Most authors recommend treatment of PE with RHT with thrombolysis or embolectomy followed by anticoagulation, although evidence is scarce. Individual risk of hemorrhage and operatory-related mortality should be taken into account when defining the treatment strategy especially when benefit is not firmly established. PMID:28469944

  17. Plasma Chemerin Levels Are Increased in ST Elevation Myocardial Infarction Patients with High Thrombus Burden.

    PubMed

    Ateş, Ahmet Hakan; Arslan, Uğur; Aksakal, Aytekin; Yanık, Ahmet; Özdemir, Metin; Kul, Selim

    2018-01-01

    To investigate plasma chemerin levels in ST elevation myocardial infarction (STEMI) patients and find out possible relationships between plasma chemerin levels and angiographic characteristics. Ninety-seven consecutive patients who presented with STEMI and underwent primary percutaneous coronary intervention (PCI) with coronary stents were enrolled, and 30 age- and sex-matched patients with stable angina pectoris who underwent coronary angiography formed the control group. Angiographic characteristics of the patients including thrombolysis in myocardial infarction (TIMI) thrombus and Gensini scores were noted. Blood samples were taken to detect several biochemical markers including plasma chemerin levels at the admission to hospital. Serum chemerin and C-reactive protein (CRP) levels were significantly increased in patients with STEMI. Among STEMI patients, serum chemerin levels were significantly higher in patients with high thrombus burden (581.5 ± 173.7 versus 451.3 ± 101.2 mg/dL, p < 0.001). CRP levels and peak creatine kinase-MB (CK-MB) levels were higher, and left ventricular ejection fraction and post-PCI TIMI flow were lower in patients with high thrombus burden. After multivariate analysis, serum chemerin levels were also higher in patients with high thrombus grade (odds ratio: 1.009 (1.005-1.014), p < 0.001). Besides, serum chemerin levels were also found to be significantly correlated with CRP ( r =0.47, p < 0.001) and peak CK-MB ( r =0.376, p < 0.001) levels. Results from our study have demonstrated for the first time that chemerin levels were higher in STEMI patients with greater thrombus burden and higher level of inflammation.

  18. Hsp-27 levels and thrombus burden relate to clinical outcomes in patients with ST-segment elevation myocardial infarction

    PubMed Central

    Tian, Maozhou; Zhu, Lingmin; Lin, Hongyang; Lin, Qiaoyan; Huang, Peng; Yu, Xiao; Jing, Yanyan

    2017-01-01

    High thrombus burden, subsequent distal embolization, and myocardial no-reflow remain a large obstacle that may negate the benefits of urgent coronary revascularization in patients with ST-segment elevation myocardial infarction (STEMI). However, the biological function and clinical association of Hsp-27 with thrombus burden and clinical outcomes in patients with STEMI is not clear. Consecutive patients (n = 146) having STEMI undergoing primary percutaneous coronary intervention (pPCI) within 12 hours from the onset of symptoms were enrolled in this prospective study in the Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shangdong, P.R. China. Patients were divided into low thrombus burden and high thrombus burden groups. The present study demonstrated that patients with high-thrombus burden had higher plasma Hsp-27 levels ([32.0 ± 8.6 vs. 58.0 ± 12.3] ng/mL, P < 0.001). The median value of Hsp-27 levels in all patients with STEMI was 45 ng/mL. Using the receiver operating characteristic (ROC) curve analysis, plasma Hsp-27 levels were of significant diagnostic value for high thrombus burden (AUC, 0.847; 95% CI, 0.775–0.918; P < 0.01). The multivariate cox regression analysis demonstrated that Hsp-27 > 45 ng/mL (HR 2.801, 95% CI 1.296–4.789, P = 0.001), were positively correlated with the incidence of major adverse cardiovascular events (MACE). Kaplan-Meier survival analysis demonstrated that MACE-free survival at 180-day follow-up was significantly lower in patients with Hsp-27 > 45 ng/mL (log rank = 10.28, P < 0.001). Our data demonstrate that plasma Hsp-27 was positively correlated with high thrombus burden and the incidence of MACE in patients with STEMI who underwent pPCI. PMID:29088740

  19. Calcified right atrial thrombus in HIV infected patient.

    PubMed

    Mwita, Julius Chacha; Goepamang, Monkgogi; Mkubwa, Jack Joseph; Gunness, Teeluck Kumar; Reebye, Deshmukh; Motumise, Kelebogile

    2013-01-01

    Calcified right atrial thrombi are rare cardiac masses that may be complicated by pulmonary embolism. Although they can be discovered by a transthoracic echocardiography, they may need histological examination to differentiate them from other cardiac masses. We report a case of a 44-year-old woman who presented with a calcified right atrial thrombus and progressive dyspnoea.

  20. Hand-assisted laparoscopic radical nephrectomy in the treatment of a renal cell carcinoma with a level II vena cava thrombus.

    PubMed

    Kovac, Jason R; Luke, Patrick P

    2010-01-01

    Excision of renal cell carcinoma (RCC) with corresponding vena cava thrombus is a technical challenge requiring open resection and vascular clamping. A 58 year old male with a right kidney tumor presented with a thrombus extending 1 cm into the vena cava. Using a hand-assisted transperitoneal approach through a 7 cm gel-port, the right kidney was dissected and the multiple vascular collaterals supplying the tumor were identified and isolated. The inferior vena cava was mobilized 4 cm cephalad and 4 cm caudal to the right renal vein. Lateral manual traction was applied to the right kidney allowing the tumor thrombus to be retracted into the renal vein, clear of the vena cava. After laparoscopic ultrasonographic confirmation of the location of the tip of the tumor thrombus, an articulating laparoscopic vascular stapler was used to staple the vena cava at the ostium of the right renal vein. This allowed removal of the tumor thrombus without the need for a Satinsky clamp. The surgery was completed in 243 minutes with no intra-operative complications. The entire kidney and tumor thrombus was removed with negative surgical margins. Estimated blood loss was 300 cc. We present a laparoscopic resection of a renal mass with associated level II thrombus using a hand-assisted approach. In patients with minimal caval involvement, our surgical approach presents an option to the traditional open resection of a renal mass.

  1. Surgical management of renal cell cancer with tumor thrombus through an exclusive transabdominal approach.

    PubMed

    González, Javier; Angulo, J; Ciancio, G

    2011-04-01

    Renal cell cancer with tumor thrombus is present in 4-15% of cases. The prognostic significance of this entity has been object of intense debate. Nowadays, it is considered, that the presence of thrombus itself does not have a negative prognostic impact on survival rates if the thrombus could be excised satisfactorily. Complete removal of renal malignant tissue is the only curative strategy for the treatment of this kind of tumors. During the last three decades, there has been steady improvements in surgical technique and preoperative care fields that have favorably modified the surgeons' ability to safely excise these tumors. In this sense, the experience provided by multiorgan, kidney-pancreas and liver procurement and transplantation techniques led the urologists reexamine their approaches to the inferior vena cava and retroperitoneum, thus they could result useful in the always challenging resection of these complex tumors with neoplasic extension into the vena cava.

  2. Investigating intermolecular forces associated with thrombus initiation using optical tweezers

    NASA Astrophysics Data System (ADS)

    Arya, Maneesh; Lopez, Jose A.; Romo, Gabriel M.; Dong, Jing-Fei; McIntire, Larry V.; Moake, Joel L.; Anvari, Bahman

    2002-05-01

    Thrombus formation occurs when a platelet membrane receptor, glycoprotein (GP) Ib-IX-V complex, binds to its ligand, von Willebrand factor (vWf), in the subendothelium or plasma. To determine which GP Ib-IX-V amino acid sequences are critical for bond formation, we have used optical tweezers to measure forces involved in the binding of vWf to GP Ib-IX-V variants. Inasmuch as GP Ib(alpha) subunit is the primary component in human GP Ib-IX-V complex that binds to vWf, and that canine GP Ib(alpha) , on the other hand, does not bind to human vWf, we progressively replaced human GP Ib(alpha) amino acid sequences with canine GP Ib(alpha) sequences to determine the sequences essential for vWf/GP Ib(alpha) binding. After measuring the adhesive forces between optically trapped, vWf-coated beads and GP Ib(alpha) variants expressed on mammalian cells, we determined that leucine- rich repeat 2 of GP Ib(alpha) was necessary for vWf/GP Ib-IX- V bond formation. We also found that deletion of the N- terminal flanking sequence and leucine-rich repeat 1 reduced adhesion strength to vWf but did not abolish binding. While divalent cations are known to influence binding of vWf, addition of 1mM CaCl2 had no effect on measured vWf/GP Ib(alpha) bond strengths.

  3. Discrimination between platelet-mediated and coagulation-mediated mechanisms in a model of complex thrombus formation in vivo

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Cadroy, Y.; Horbett, T.A.; Hanson, S.R.

    1989-04-01

    To study mechanisms of complex thrombus formation in vivo, and to compare the relative antithrombotic effects of anticoagulants and antiplatelet agents, a model was developed in baboons. Segments of collagen-coated tubing followed by two sequentially placed expansion chambers exhibiting disturbed flow patterns were exposed to native blood under laminar flow conditions. The device was incorporated for 1 hour into an exteriorized arteriovenous shunt in baboons under controlled blood flow (20 ml/min). Morphologic evaluation by scanning electron microscopy showed that thrombi associated with collagen were relatively rich in platelets but thrombi in the chambers were rich in fibrin and red cells.more » Deposition of indium 111-labeled platelets was continuously measured with a scintillation camera. Platelet deposition increased in a linear (collagen-coated segment) or exponential (chambers 1 and 2) fashion over time, with values after 40 minutes averaging 24.1 +/- 3.3 x 10(8) platelets (collagen segment), 16.7 +/- 3.4 x 10(8) platelets (chamber 1), and 8.4 +/- 2.4 x 10(8) platelets (chamber 2). Total fibrinogen deposition after 40 minutes was determined by using iodine 125-labeled baboon fibrinogen and averaged 0.58 +/- 0.14 mg in the collagen segment, 1.51 +/- 0.27 mg in chamber 1, and 0.95 +/- 0.25 mg in chamber 2. Plasma levels of beta-thromboglobulin (beta TG), platelet-factor 4 (PF4), and fibrinopeptide A (FPA) increased fourfold to fivefold after 60 minutes of blood exposure to the thrombotic device. Platelet deposition onto the collagen segment, chamber 1, and chamber 2 was linearly dependent on the circulating platelet count. Platelet accumulation in chamber 1 and chamber 2 was also dependent on the presence of the proximal collagen segment.« less

  4. Huge ascending aortic aneurysm with an intraluminal thrombus in an embolic event-free patient

    PubMed Central

    Parato, Vito Maurizio; Pezzuoli, Franco; Labanti, Benedetto; Baboci, Arben

    2015-01-01

    We present a case of an 87-year-old male patient with a huge ascending aortic aneurysm, filled by a huge thrombus most probably due to previous dissection. This finding was detected by two-dimensional transthoracic echocardiography and contrast-enhanced computed tomography (CT) angiography scan. The patient refused surgical treatment and was medically treated. Despite the huge and mobile intraluminal thrombus, the patient remained embolic event-free up to 6 years later, and this makes the case unique. PMID:25838924

  5. Adrenocortical carcinoma with inferior vena cava, left renal vein and right atrium tumor thrombus extension

    PubMed Central

    Annamaria, Pronio; Silvia, Piroli; Bernardo, Ciamberlano; Alessandro, De Luca; Antonino, Marullo; Antonio, Barretta; Giuseppe, Mazzesi; Massimo, Rossi; Montesani, Chiara

    2015-01-01

    Introduction Adrenocortical carcinoma (ACC) is a rare, but highly aggressive type of tumor with an annual incidence of 1–2 cases per million. The prognosis is poor with a five-year overall survival rate of ∼35%. The poor prognosis may be related to the advanced stage at which the majority of ACCs are detected. Complete surgical resection remains the most effective treatment. Presentation of the case A 51-year-old female patient with recent onset of dyspepsia, ascites and peripheral edema was referred to our institution. Computed tomography (CT) and Magnetic Resonance Imaging (MRI) displayed a 8 cm Ø right adrenal mass. Moreover a tumor thrombus jutted out into the IVC, left renal vein and right atrium. An echocardiographic evaluation confirmed the presence of the tumor thrombus in the right atrium. The patient underwent adrenalectomy with removal of its intravascular extension with the assistance of cardiopulmonary bypass and hypothermia. Discussion ACC is a rare malignancy and ACC with tumor thrombus extension is a rare presentation. Patients can present with a variety of sign and symptoms, depending on the extent of the tumor. CT scan of chest and abdomen represents the gold standard in ACC staging while magnetic resonance imaging (MRI) is preferred for tumor thrombus characterization. Complete surgical resection with a negative margin, R0 resection, is the only curative option for localized disease. Kidney sparing surgery should be performed when possible. Conclusion We present a rare case of Adrenocortical carcinoma with tumor thrombus extending into the IVC and right atrium. Complete resection with negative margins represents the best therapeutic chance for these patients. PMID:26355237

  6. Adrenocortical carcinoma with inferior vena cava, left renal vein and right atrium tumor thrombus extension.

    PubMed

    Annamaria, Pronio; Silvia, Piroli; Bernardo, Ciamberlano; Alessandro, De Luca; Antonino, Marullo; Antonio, Barretta; Giuseppe, Mazzesi; Massimo, Rossi; Montesani, Chiara

    2015-01-01

    Adrenocortical carcinoma (ACC) is a rare, but highly aggressive type of tumor with an annual incidence of 1-2 cases per million. The prognosis is poor with a five-year overall survival rate of ∼35%. The poor prognosis may be related to the advanced stage at which the majority of ACCs are detected. Complete surgical resection remains the most effective treatment. A 51-year-old female patient with recent onset of dyspepsia, ascites and peripheral edema was referred to our institution. Computed tomography (CT) and Magnetic Resonance Imaging (MRI) displayed a 8cm Ø right adrenal mass. Moreover a tumor thrombus jutted out into the IVC, left renal vein and right atrium. An echocardiographic evaluation confirmed the presence of the tumor thrombus in the right atrium. The patient underwent adrenalectomy with removal of its intravascular extension with the assistance of cardiopulmonary bypass and hypothermia. ACC is a rare malignancy and ACC with tumor thrombus extension is a rare presentation. Patients can present with a variety of sign and symptoms, depending on the extent of the tumor. CT scan of chest and abdomen represents the gold standard in ACC staging while magnetic resonance imaging (MRI) is preferred for tumor thrombus characterization. Complete surgical resection with a negative margin, R0 resection, is the only curative option for localized disease. Kidney sparing surgery should be performed when possible. We present a rare case of Adrenocortical carcinoma with tumor thrombus extending into the IVC and right atrium. Complete resection with negative margins represents the best therapeutic chance for these patients. Copyright © 2015. Published by Elsevier Ltd.

  7. Exogenous modification of platelet membranes with the omega-3 fatty acids EPA and DHA reduces platelet procoagulant activity and thrombus formation.

    PubMed

    Larson, Mark K; Tormoen, Garth W; Weaver, Lucinda J; Luepke, Kristen J; Patel, Ishan A; Hjelmen, Carl E; Ensz, Nicole M; McComas, Leah S; McCarty, Owen J T

    2013-02-01

    Several studies have implicated the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in inhibition of normal platelet function, suggesting a role for platelets in EPA- and DHA-mediated cardioprotection. However, it is unclear whether the cardioprotective mechanisms arise from alterations to platelet-platelet, platelet-matrix, or platelet-coagulation factor interactions. Our previous results led us to hypothesize that EPA and DHA alter the ability of platelets to catalyze the generation of thrombin. We tested this hypothesis by exogenously modifying platelet membranes with EPA and DHA, which resulted in compositional changes analogous to increased dietary EPA and DHA intake. Platelets treated with EPA and DHA showed reductions in the rate of thrombin generation and exposure of platelet phosphatidylserine. In addition, treatment of platelets with EPA and DHA decreased thrombus formation and altered the processing of thrombin precursor proteins. Furthermore, treatment of whole blood with EPA and DHA resulted in increased occlusion time and a sharply reduced accumulation of fibrin under flow conditions. These results demonstrate that EPA and DHA inhibit, but do not eliminate, the ability of platelets to catalyze thrombin generation in vitro. The ability of EPA and DHA to reduce the procoagulant function of platelets provides a possible mechanism behind the cardioprotective phenotype in individuals consuming high levels of EPA and DHA.

  8. P2Y12 regulates platelet adhesion/activation, thrombus growth, and thrombus stability in injured arteries

    PubMed Central

    André, Patrick; Delaney, Suzanne M.; LaRocca, Thomas; Vincent, Diana; DeGuzman, Francis; Jurek, Marzena; Koller, Beverley; Phillips, David R.; Conley, Pamela B.

    2003-01-01

    The critical role for ADP in arterial thrombogenesis was established by the clinical success of P2Y12 antagonists, currently used at doses that block 40–50% of the P2Y12 on platelets. This study was designed to determine the role of P2Y12 in platelet thrombosis and how its complete absence affects the thrombotic process. P2Y12-null mice were generated by a gene-targeting strategy. Using an in vivo mesenteric artery injury model and real-time continuous analysis of the thrombotic process, we observed that the time for appearance of first thrombus was delayed and that only small, unstable thrombi formed in P2Y12–/– mice without reaching occlusive size, in the absence of aspirin. Platelet adhesion to vWF was impaired in P2Y12–/– platelets. While adhesion to fibrinogen and collagen appeared normal, the platelets in thrombi from P2Y12–/– mice on collagen were less dense and less activated than their WT counterparts. P2Y12–/– platelet activation was also reduced in response to ADP or a PAR-4–activating peptide. Thus, P2Y12 is involved in several key steps of thrombosis: platelet adhesion/activation, thrombus growth, and stability. The data suggest that more aggressive strategies of P2Y12 antagonism will be antithrombotic without the requirement of aspirin cotherapy and may provide benefits even to the aspirin-nonresponder population. PMID:12897207

  9. Dust formation and wind acceleration around the aluminum oxide-rich AGB star W Hydrae

    NASA Astrophysics Data System (ADS)

    Takigawa, Aki; Kamizuka, Takafumi; Tachibana, Shogo; Yamamura, Issei

    2017-11-01

    Dust grains, formed around asymptotic giant branch (AGB) stars, are accelerated by stellar radiation to drive stellar winds, which supply freshly synthesized nuclides to the Galaxy. Silicate is the dominant dust species in space, but 40% of oxygen-rich AGB stars are thought to have comparable amounts of aluminum oxide dust. Dust formation and the wind-driving mechanism around these oxygen-rich stars, however, are poorly understood. We report on the spatial distributions of AlO and 29SiO molecules around an aluminum oxide-rich M-type AGB star, W Hydrae, based on observations obtained with the Atacama Large Millimeter/submillimeter Array. AlO molecules were only observed within three stellar radii (Rstar), whereas 29SiO was distributed in the accelerated wind beyond 5 Rstar without significant depletion. This strongly suggests that condensed aluminum oxide dust plays a key role in accelerating the stellar wind and in preventing the efficient formation of silicate dust around W Hydrae.

  10. Dust formation and wind acceleration around the aluminum oxide–rich AGB star W Hydrae

    PubMed Central

    Takigawa, Aki; Kamizuka, Takafumi; Tachibana, Shogo; Yamamura, Issei

    2017-01-01

    Dust grains, formed around asymptotic giant branch (AGB) stars, are accelerated by stellar radiation to drive stellar winds, which supply freshly synthesized nuclides to the Galaxy. Silicate is the dominant dust species in space, but ~40% of oxygen-rich AGB stars are thought to have comparable amounts of aluminum oxide dust. Dust formation and the wind-driving mechanism around these oxygen-rich stars, however, are poorly understood. We report on the spatial distributions of AlO and 29SiO molecules around an aluminum oxide–rich M-type AGB star, W Hydrae, based on observations obtained with the Atacama Large Millimeter/submillimeter Array. AlO molecules were only observed within three stellar radii (Rstar), whereas 29SiO was distributed in the accelerated wind beyond 5 Rstar without significant depletion. This strongly suggests that condensed aluminum oxide dust plays a key role in accelerating the stellar wind and in preventing the efficient formation of silicate dust around W Hydrae. PMID:29109978

  11. Can eccentric arterial plaques alone cause flow stagnation points and favour thrombus incorporation?

    PubMed Central

    Beneli, Cristina T; Barbosa, Priscila F; Floriano, Elaine M; Abreu, Mônica A; Ramalho, Fernando S; Júnior, Jorge Elias; Rossi, Marcos A; Ramos, Simone G

    2009-01-01

    We have used an experimental model of aorta stenosis, with a Plexiglas plug, simulating a stable atheromatous plaque that promotes local turbulence and thrombosis. With animal survival of more than 24 h, we followed the partial fibrinolysis of the thrombus as well as its posterior organization and incorporation to the arterial wall as a neointima for up to 30 days. The mushroom plug form permitted the development of recirculation and stasis areas around it, favouring this evolution. Despite noted limitations, this study demonstrates that thrombus incorporation can contribute to plaque extension, as it can promote recirculation and stasis areas. PMID:19563612

  12. Platelet activation independent of pulmonary inflammation contributes to diesel exhaust particulate-induced promotion of arterial thrombosis.

    PubMed

    Tabor, Caroline M; Shaw, Catherine A; Robertson, Sarah; Miller, Mark R; Duffin, Rodger; Donaldson, Ken; Newby, David E; Hadoke, Patrick W F

    2016-02-09

    Accelerated thrombus formation induced by exposure to combustion-derived air pollution has been linked to alterations in endogenous fibrinolysis and platelet activation in response to pulmonary and systemic inflammation. We hypothesised that mechanisms independent of inflammation contribute to accelerated thrombus formation following exposure to diesel exhaust particles (DEP). Thrombosis in rats was assessed 2, 6 and 24 h after administration of DEP, carbon black (CB; control carbon nanoparticle), DQ12 quartz microparticles (to induce pulmonary inflammation) or saline (vehicle) by either intra-tracheal instillation (0.5 mg, except Quartz; 0.125 mg) or intravenous injection (0.5 mg/kg). Thrombogenicity was assessed by carotid artery occlusion, fibrinolytic variables and platelet-monocyte aggregates. Measures of inflammation were determined in plasma and bronchoalveolar lavage fluid. Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI)-1 were measured following direct in vitro exposure of human umbilical vein endothelial cells (HUVECs) to DEP (10-150 μg/mL). Instillation of DEP reduced the time to thrombotic occlusion in vivo, coinciding with the peak of DEP-induced pulmonary inflammation (6 h). CB and DQ12 produced greater inflammation than DEP but did not alter time to thrombotic occlusion. Intravenous DEP produced an earlier (2 h) acceleration of thrombosis (as did CB) without pulmonary or systemic inflammation. DEP inhibited t-PA and PAI-1 release from HUVECs, and reduced the t-PA/PAI-1 ratio in vivo; similar effects in vivo were seen with CB and DQ12. DEP, but not CB or DQ12, increased platelet-monocyte aggregates. DEP accelerates arterial thrombus formation through increased platelet activation. This effect is dissociated from pulmonary and systemic inflammation and from impaired fibrinolytic function.

  13. Incidence and Outcomes of Inferior Vena Cava Filter Thrombus during Catheter-directed Thrombolysis for Proximal Deep Venous Thrombosis.

    PubMed

    Jiang, Jianguang; Tu, Jianfei; Jia, Zhongzhi; Chen, Jiezhong; Cao, Haitao; Meng, Qingli; Fuller, Tyler A; Tian, Feng

    2017-01-01

    The aim of the study was to retrospectively evaluate the incidence and outcomes of inferior vena cava (IVC) filter thrombus during catheter-directed thrombolysis (CDT) for acute proximal deep venous thrombosis (DVT). From October 2006 to June 2015, patients diagnosed with acute proximal DVT and received CDT after a retrievable IVC filter was placed were included. The incidence, treatment, and outcomes of IVC filter thrombus during CDT were recorded and analyzed. A total of 189 patients (91 women, 98 men; mean age, 57.6 ± 9.8 years; range, 24-85 years) were included in this study. Among the 189 cases, the DVTs involved popliteal iliofemoral veins in 54 patients, iliofemoral veins in 113 patients, and iliac veins in 22 patients, of which 18 patients had thrombus extended into the IVC. Of the 189 patients, a total of 8 (4.2%, 8 of 189) patients were identified with IVC filter thrombus during CDT. The IVC filter thrombus was detected on a median of 2 days (range, 2-4 days) of CDT therapy, including small-size (n = 6) and large-size (n = 2) filter thrombus. Of the 8 patients, CDTs were performed with a mean 7.6 ± 1.1 days (range, 6-11 days) after the presence of symptoms for the treatment of proximal DVT, and all the IVC filter thrombi were lysed during CDT for the proximal DVT. All the IVC filters were removed successfully with a mean of 12.8 ± 0.93 days from placement. There were no procedure- or thrombolysis-related major complications, and no symptomatic pulmonary embolism breakthrough was seen in any of the patients after the filter placement. IVC filter thrombus during CDT for the acute proximal DVT is uncommon, and all of them did not need any additional treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. An ischemic stroke patient with free floating thrombus in carotid artery, successfully treated by open carotid thrombectomy: a first case report in Nepal.

    PubMed

    Shrestha, Prabin; Adhikari, Rupendra; Tamrakar, Samantha; Pant, Basanta; Koirala, Bhagwan; Yamaguchi, Satoshi; Kurisu, Kaoru

    2012-12-01

    Free floating thrombus in the carotid artery is a well-known phenomenon, though relatively rare. We present a case in which we performed open surgery and achieved successful retrieval of the thrombus. A 40 year-old male patient presented with ischemic stroke and mild left hemiparesis. Computerized tomography and magnetic resonance imaging showed infarction in the right parieto-occipital area. Carotid Doppler study showed carotid stenosis on the right side. Further investigation with CT angiography of the neck vessels confirmed significant carotid artery occlusion with a free-floating thrombus in the internal carotid artery. Carotid endarterectomy was planned under EEG monitoring. The right carotid artery was exposed with a vertical incision along the medial margin of the sternocleido-mastoid muscle. The carotid artery was opened and, as expected, showed a soft, mobile thrombus. Thus thrombectomy was planned. A 2 Fr fogarty catheter was introduced distal to the thrombus, the balloon was inflated and pulled back gently, which removed the thrombus completely. There was no postoperative complication and the patient is fine at 1 year follow-up.

  15. Synthesis of PEGylated polyglutamic acid peptide dendrimer and its application in dissolving thrombus.

    PubMed

    Zhang, Shao-Fei; Gao, Chunmei; Lü, Shaoyu; He, Jiujun; Liu, Mingzhu; Wu, Can; Liu, Yijing; Zhang, Xinyu; Liu, Zhen

    2017-11-01

    Nattokinase (NK) has been used as a new generation thrombolytic drug, due to its high safety, low cost and low side effects. However, it is sensitive to external environment and may lose the enzyme activity easily. Peptide dendrimer possesses functional groups on its surface, adjustable sizes, biodegradability, biocompatibility, and low toxicity, which could be used as ideal carrier for drug protection and delivery. Demonstrated for the first time in this paper, a PEGylated dendrimer (G n -PEG-G n ) composed of polyglutamic acid is designed and synthesized as delivery platform of NK for thrombus treatment. A panel of PEGylated dendrimers with three different generations of 2, 3, 4 was prepared to investigate the effect of dendrimer architecture on the properties and therapeutic efficacy of the resultant NK-loaded delivery systems in terms of the morphology, dimension and enzyme activity. The results demonstrated that the NK-loaded G 3 -PEG-G 3 (G 3 -PEG-G 3 /NK ratio of 6/1), of all the formulations, displayed the optimal enzyme activity for dissolving thrombus in vitro, thus offering great potential for the treatment of thrombus. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Right ventricular thrombus with Behçet's syndrome: successful treatment with warfarin and immunosuppressive agents.

    PubMed

    Dogan, Sait M; Birdane, Alparslan; Korkmaz, Cengiz; Ata, Necmi; Timuralp, Bilgin

    2007-01-01

    Behçet's syndrome is a chronic multisystem disease that presents with recurrent oral and genital ulceration and recurrent uveitis. Cardiac involvement is an extremely rare manifestation of this disorder. A 33-year-old man with Behçet's syndrome was admitted to our department with a history of cough, fever, chest pain, hemoptysis, and weight loss. Transthoracic and transesophageal echocardiography revealed a right ventricular thrombus. After 1 month of treatment with warfarin, cyclophosphamide, and corticosteroid, the intracardiac thrombus resolved.

  17. Fully automatic detection and segmentation of abdominal aortic thrombus in post-operative CTA images using Deep Convolutional Neural Networks.

    PubMed

    López-Linares, Karen; Aranjuelo, Nerea; Kabongo, Luis; Maclair, Gregory; Lete, Nerea; Ceresa, Mario; García-Familiar, Ainhoa; Macía, Iván; González Ballester, Miguel A

    2018-05-01

    Computerized Tomography Angiography (CTA) based follow-up of Abdominal Aortic Aneurysms (AAA) treated with Endovascular Aneurysm Repair (EVAR) is essential to evaluate the progress of the patient and detect complications. In this context, accurate quantification of post-operative thrombus volume is required. However, a proper evaluation is hindered by the lack of automatic, robust and reproducible thrombus segmentation algorithms. We propose a new fully automatic approach based on Deep Convolutional Neural Networks (DCNN) for robust and reproducible thrombus region of interest detection and subsequent fine thrombus segmentation. The DetecNet detection network is adapted to perform region of interest extraction from a complete CTA and a new segmentation network architecture, based on Fully Convolutional Networks and a Holistically-Nested Edge Detection Network, is presented. These networks are trained, validated and tested in 13 post-operative CTA volumes of different patients using a 4-fold cross-validation approach to provide more robustness to the results. Our pipeline achieves a Dice score of more than 82% for post-operative thrombus segmentation and provides a mean relative volume difference between ground truth and automatic segmentation that lays within the experienced human observer variance without the need of human intervention in most common cases. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. A systems approach to hemostasis: 3. Thrombus consolidation regulates intrathrombus solute transport and local thrombin activity

    PubMed Central

    Welsh, John D.; Tomaiuolo, Maurizio; Wu, Jie; Colace, Thomas V.; Diamond, Scott L.

    2014-01-01

    Hemostatic thrombi formed after a penetrating injury have a distinctive structure in which a core of highly activated, closely packed platelets is covered by a shell of less-activated, loosely packed platelets. We have shown that differences in intrathrombus molecular transport emerge in parallel with regional differences in platelet packing density and predicted that these differences affect thrombus growth and stability. Here we test that prediction in a mouse vascular injury model. The studies use a novel method for measuring thrombus contraction in vivo and a previously characterized mouse line with a defect in integrin αIIbβ3 outside-in signaling that affects clot retraction ex vivo. The results show that the mutant mice have a defect in thrombus consolidation following vascular injury, resulting in an increase in intrathrombus transport rates and, as predicted by computational modeling, a decrease in thrombin activity and platelet activation in the thrombus core. Collectively, these data (1) demonstrate that in addition to the activation state of individual platelets, the physical properties of the accumulated mass of adherent platelets is critical in determining intrathrombus agonist distribution and platelet activation and (2) define a novel role for integrin signaling in the regulation of intrathrombus transport rates and localization of thrombin activity. PMID:24951426

  19. Novel risk predictor for thrombus deposition in abdominal aortic aneurysms

    NASA Astrophysics Data System (ADS)

    Nestola, M. G. C.; Gizzi, A.; Cherubini, C.; Filippi, S.; Succi, S.

    2015-10-01

    The identification of the basic mechanisms responsible for cardiovascular diseases stands as one of the most challenging problems in modern medical research including various mechanisms which encompass a broad spectrum of space and time scales. Major implications for clinical practice and pre-emptive medicine rely on the onset and development of intraluminal thrombus in which effective clinical therapies require synthetic risk predictors/indicators capable of informing real-time decision-making protocols. In the present contribution, two novel hemodynamics synthetic indicators, based on a three-band decomposition (TBD) of the shear stress signal, are introduced. Extensive fluid-structure computer simulations of patient-specific scenarios confirm the enhanced risk-prediction capabilities of the TBD indicators. In particular, they permit a quantitative and accurate localization of the most likely thrombus deposition in realistic aortic geometries, where previous indicators would predict healthy operation. The proposed methodology is also shown to provide additional information and discrimination criteria on other factors of major clinical relevance, such as the size of the aneurysm.

  20. Prediction of Thrombus Growth: Effect of Stenosis and Reynolds Number.

    PubMed

    Hosseinzadegan, Hamid; Tafti, Danesh K

    2017-06-01

    Shear stresses play a major role in platelet-substrate interactions and thrombus formation and growth in blood flow, where under both pathological and physiological conditions platelet adhesion and accumulation occur. In this study, a shear-dependent continuum model for platelet activation, adhesion and aggregation is presented. The model was first verified under three different shear conditions and at two heparin levels. Three-dimensional simulations were then carried out to evaluate the performance of the model for severely damaged (stripped) aortas with mild and severe stenosis degrees in laminar flow regime. For these cases, linear shear-dependent functions were developed for platelet-surface and platelet-platelet adhesion rates. It was confirmed that the platelet adhesion rate is not only a function of Reynolds number (or wall shear rate) but also the stenosis severity of the vessel. General correlations for adhesion rates of platelets as functions of stenosis and Reynolds number were obtained based on these cases. Finally using the new platelet adhesion rates, the model was applied to different experimental systems and shown to agree well with measured platelet deposition.

  1. Thrombus just beneath a retrievable inferior vena cava filter in a pregnant woman with deep vein thrombosis: its removal requiring catheter thrombus fragmentation with fibrinolysis.

    PubMed

    Horie, Kenji; Suzuki, Hirotada; Ohkuchi, Akihide; Matsubara, Shigeki; Ikemoto, Tomokazu; Suzuki, Mitsuaki

    2014-02-01

    Recently, transient inferior vena cava (IVC) filters have been employed to protect against pulmonary embolism (PE) in pregnant women with deep vein thrombosis. A 34-year-old primiparous Japanese woman with a history of myomectomy was diagnosed with deep vein thrombosis by ultrasound at 27 weeks of gestation. Unfractionated heparin was administered, which soon ameliorated swelling in the right thigh. A transient IVC filter was implanted just before cesarean section. An enhanced computed tomography scan 2 days after cesarean section revealed a wide thrombus just distal to the filter. We performed catheter thrombus fragmentation with fibrinolysis just before the removal of the IVC filter, resulting in re-canalization of blood flow. No significant PE occurred. Although a transient IVC filter may work well for the prophylaxis of PE during labor and delivery, catheter fragmentation with fibrinolysis may become necessary at removal of the filter. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

  2. A rare but serious manifestation of Behçet's disease: intracardiac thrombus in 22 patients.

    PubMed

    Emmungil, Hakan; Yaşar Bilge, N Şule; Küçükşahin, Orhan; Kılıç, Levent; Okutucu, Sercan; Gücenmez, Sercan; Kalyoncu, Umut; Kaşifoğlu, Timuçin; Turgay, Murat; Aksu, Kenan

    2014-01-01

    Behçet's disease (BD) is a chronic, multisystemic disorder characterised by recurrent oral aphtous ulcers, genital ulcers and ocular inflammation. Vasculitis and thrombotic events are the most important causes of mortality. Vena cava thrombosis, pulmonary artery aneurysms, Budd-Chiari syndrome, peripheral artery aneurysms, dural sinus thrombosis and abdominal aorta aneurysms are the other less common vascular manifestations of BD. Cardiac involvement in BD is a rare and life-threatening complication. The aim of this study was to assess the clinical characteristics and outcome of patients with BD who have intracardiac thrombus. The hospital files of BD patients followed by rheumatology clinics of four medical centres (Ankara University, Ege University, Hacettepe University and Eskişehir Osmangazi University Hospitals) were retrospectively evaluated. Data included patients' demographic and clinical features, laboratory findings and outcome. All patients fulfilled three or more of the International Study Group Criteria for BD. Twenty-two patients with intracardiac thrombus were evaluated. The mean age of patients with intracardiac thrombosis was 29.1 yrs (22-44) and there was a male predominance with a ratio of 20:2. Cardiac involvement was the first clinical manifestation of BD in 9 of the 22 patients. Initial symptoms of the patients were fever (n=18, 81%), dyspnea (n=9, 40%) chest pain (n=9, 40%) and haemoptysis (n=7, 31.8%). Sixteen patients (72%) had pulmonary arteritis and 10 (45%) patients had venous system lesions included deep vein, inferior vena cava and hepatic vein. Intra-cardiac thrombus were found only in the right cavities in 17 patients (77%), only in the left cavities in 2 patients (9%), and in both left and right cavities of the heart in 3 patients (13.6%). Once the cardiac lesion was diagnosed as a complication of BD, high dose (1mg/kg/d) prednisone (n=22, 100%) plus cyclophosphamide (n=18, 81%) or azathioprine (n=3, 13.6%) and warfarin (n=8, 36

  3. 18F-fluorodeoxyglucose positron emission tomography/computed tomography enables the detection of recurrent same-site deep vein thrombosis by illuminating recently formed, neutrophil-rich thrombus.

    PubMed

    Hara, Tetsuya; Truelove, Jessica; Tawakol, Ahmed; Wojtkiewicz, Gregory R; Hucker, William J; MacNabb, Megan H; Brownell, Anna-Liisa; Jokivarsi, Kimmo; Kessinger, Chase W; Jaff, Michael R; Henke, Peter K; Weissleder, Ralph; Jaffer, Farouc A

    2014-09-23

    Accurate detection of recurrent same-site deep vein thrombosis (DVT) is a challenging clinical problem. Because DVT formation and resolution are associated with a preponderance of inflammatory cells, we investigated whether noninvasive (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) imaging could identify inflamed, recently formed thrombi and thereby improve the diagnosis of recurrent DVT. We established a stasis-induced DVT model in murine jugular veins and also a novel model of recurrent stasis DVT in mice. C57BL/6 mice (n=35) underwent ligation of the jugular vein to induce stasis DVT. FDG-PET/computed tomography (CT) was performed at DVT time points of day 2, 4, 7, 14, or 2+16 (same-site recurrent DVT at day 2 overlying a primary DVT at day 16). Antibody-based neutrophil depletion was performed in a subset of mice before DVT formation and FDG-PET/CT. In a clinical study, 38 patients with lower extremity DVT or controls undergoing FDG-PET were analyzed. Stasis DVT demonstrated that the highest FDG signal occurred at day 2, followed by a time-dependent decrease (P<0.05). Histological analyses demonstrated that thrombus neutrophils (P<0.01), but not macrophages, correlated with thrombus PET signal intensity. Neutrophil depletion decreased FDG signals in day 2 DVT in comparison with controls (P=0.03). Recurrent DVT demonstrated significantly higher FDG uptake than organized day 14 DVT (P=0.03). The FDG DVT signal in patients also exhibited a time-dependent decrease (P<0.01). Noninvasive FDG-PET/CT identifies neutrophil-dependent thrombus inflammation in murine DVT, and demonstrates a time-dependent signal decrease in both murine and clinical DVT. FDG-PET/CT may offer a molecular imaging strategy to accurately diagnose recurrent DVT. © 2014 American Heart Association, Inc.

  4. Acute Left Arm Ischemia Associated with Floating Thrombus in the Proximal Descending Aorta: Combined Endovascular and Surgical Therapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fanelli, F., E-mail: fabrizio.fanelli@uniroma1.it; Gazzetti, M.; Boatta, E.

    Free floating thrombus in the proximal descending aorta is an uncommon and dangerous condition that can be associated with acute peripheral embolization. The few cases described were solved with surgical and/or medical therapy. We report the case of a patient with acute left arm ischemia secondary to the presence of floating thrombus in the proximal descending aorta extending into the left subclavian artery, solved with combined endovascular and surgical therapy. Treatment was successfully performed with thrombembolectomy combined with temporary deployment, into the descending aorta, of a Wallstent in a 'basket-fashion' to avoid distal embolization secondary to thrombus fragmentation. At 1more » year follow-up the patient remained symptom-free.« less

  5. Blood clots are rapidly assembled hemodynamic sensors: Flow arrest triggers intraluminal thrombus contraction

    PubMed Central

    Muthard, Ryan W.; Diamond, Scott L.

    2012-01-01

    Objective Blood clots form under flow during intravascular thrombosis or vessel leakage. Prevailing hemodynamics influence thrombus structure and may regulate contraction processes. A microfluidic device capable of flowing human blood over a side channel plugged with collagen (± tissue factor) was used to measure thrombus permeability (κ) and contraction at controlled transthrombus pressure drops. Methods and Results The collagen (κcollagen = 1.98 × 10−11 cm2) supported formation of a 20-μm thick platelet layer, which unexpectedly underwent massive platelet retraction upon flow arrest. This contraction resulted in a 5.34-fold increase in permeability due to collagen restructuring. Without stopping flow, platelet deposits (no fibrin) had a permeability of κplatelet = 5.45 × 10−14 cm2 and platelet-fibrin thrombi had κthrombus = 2.71 × 10−14 cm2 for ΔP = 20.7 to 23.4 mm-Hg, the first ever measurements for clots formed under arterial flow (1130 s−1 wall shear rate). Platelet sensing of flow cessation triggered a 4.6 to 6.5-fold (n=3, P<0.05) increase in contraction rate, which was also observed in a rigid, impermeable parallel-plate microfluidic device. This triggered contraction was blocked by the myosin IIA inhibitor blebbistatin and by inhibitors of thromboxane (TXA2) and ADP signaling. In addition, flow arrest triggered platelet intracellular calcium mobilization, which was blocked by TXA2/ADP inhibitors. As clots become occlusive or vessels rupture, flow around developed clots diminishes facilitating full platelet retraction and hemostasis. Conclusion Flow dilution of ADP and thromboxane regulates platelet contractility with prevailing hemodynamics, a newly defined flow sensing mechanism to regulate clot function. PMID:23087356

  6. Human Neutrophil Peptides Mediate Endothelial-Monocyte Interaction, Foam Cell Formation, and Platelet Activation

    PubMed Central

    Quinn, Kieran L.; Henriques, Melanie; Tabuchi, Arata; Han, Bing; Yang, Hong; Cheng, Wei-Erh; Tole, Soumitra; Yu, Hanpo; Luo, Alice; Charbonney, Emmanuel; Tullis, Elizabeth; Lazarus, Alan; Robinson, Lisa A.; Ni, Heyu; Peterson, Blake R.; Kuebler, Wolfgang M.; Slutsky, Arthur S.; Zhang, Haibo

    2016-01-01

    Objective Neutrophils are involved in the inflammatory responses during atherosclerosis. Human neutrophil peptides (HNPs) released from activated neutrophils exert immune modulating properties. We hypothesized that HNPs play an important role in neutrophil-mediated inflammatory cardiovascular responses in atherosclerosis. Methods and Results We examined the role of HNPs in endothelial-leukocyte interaction, platelet activation, and foam cell formation in vitro and in vivo. We demonstrated that stimulation of human coronary artery endothelial cells with clinically relevant concentrations of HNPs resulted in monocyte adhesion and transmigration; induction of oxidative stress in human macrophages, which accelerates foam cell formation; and activation and aggregation of human platelets. The administration of superoxide dismutase or anti-CD36 antibody reduced foam cell formation and cholesterol efflux. Mice deficient in double genes of low-density lipoprotein receptor and low-density lipoprotein receptor–related protein (LRP), and mice deficient in a single gene of LRP8, the only LRP phenotype expressed in platelets, showed reduced leukocyte rolling and decreased platelet aggregation and thrombus formation in response to HNP stimulation. Conclusion HNPs exert proatherosclerotic properties that appear to be mediated through LRP8 signaling pathways, suggesting an important role for HNPs in the development of inflammatory cardiovascular diseases. PMID:21817096

  7. Oncological outcomes after cytoreductive nephrectomy for patients with metastatic renal cell carcinoma with inferior vena caval tumor thrombus.

    PubMed

    Miyake, Hideaki; Sugiyama, Takayuki; Aki, Ryota; Matsushita, Yuto; Tamura, Keita; Motoyama, Daisuke; Ito, Toshiki; Otsuka, Atsushi

    2018-06-01

    To evaluate the oncological outcomes of patients with metastatic renal cell carcinoma (mRCC) involving the inferior vena cava (IVC) who received cytoreductive nephrectomy. This study included 75 consecutive metastatis renal cell carcinoma (mRCC) patients with inferior vena cava (IVC) tumor thrombus undergoing cytoreductive nephrectomy and tumor thrombectomy followed by systemic therapy. Of the 75 patients, 11, 33, 24 and 7 had level I, II, III and IV IVC thrombus, respectively. Following surgical treatment, 25 (group A), 27 (group B) and 23 (group C) received cytokine therapy alone, molecular-targeted therapy alone and both therapies, respectively, as management for metastatic diseases. The median overall survival (OS) of the 75 patients was 16.2 months. No significant differences in OS were noted according to the level of the IVC tumor thrombus. There were no significant differences in OS among groups A, B and C; however, OS in groups B and C was significantly superior to that in group A. Furthermore, multivariate analysis of several parameters identified the following independent predictors of poor OS-elevated C-reactive protein, liver metastasis and postoperative treatment with cytokine therapy alone. The prognosis of mRCC patients with IVC thrombus undergoing cytoreductive nephrectomy may be significantly affected by the type of postoperative systemic therapy rather than the level of the IVC tumor thrombus. Accordingly, cytoreductive nephrectomy should be considered as a major therapeutic option for patients with mRCC involving the IVC, particularly in the era of targeted therapy.

  8. Deficiency of Src homology 2 domain–containing inositol 5-phosphatase 1 affects platelet responses and thrombus growth

    PubMed Central

    Séverin, Sonia; Gratacap, Marie-Pierre; Lenain, Nadège; Alvarez, Laetitia; Hollande, Etienne; Penninger, Josef M.; Gachet, Christian; Plantavid, Monique; Payrastre, Bernard

    2007-01-01

    Platelets are critical for normal hemostasis. Their deregulation can lead to bleeding or to arterial thrombosis, a primary cause of heart attack and ischemic stroke. Src homology 2 domain–containing inositol 5-phosphatase 1 (SHIP1) is a 5-phosphatase capable of dephosphorylating the phosphatidylinositol 3,4,5-trisphosphate second messenger into phosphatidylinositol 3,4-bisphosphate. SHIP1 plays a critical role in regulating the level of these 2 lipids in platelets. Using SHIP1-deficient mice, we found that its loss affects platelet aggregation in response to several agonists with minor effects on fibrinogen binding and β3 integrin tyrosine phosphorylation. Accordingly, SHIP1-null mice showed defects in arterial thrombus formation in response to a localized laser-induced injury. Moreover, these mice had a prolonged tail bleeding time. Upon stimulation, SHIP1-deficient platelets showed large membrane extensions, abnormalities in the open canalicular system, and a dramatic decrease in close cell-cell contacts. Interestingly, SHIP1 appeared to be required for platelet contractility, thrombus organization, and fibrin clot retraction. These data indicate that SHIP1 is an important element of the platelet signaling machinery to support normal hemostasis. To our knowledge, this is the first report unraveling an important function of SHIP1 in the activation of hematopoietic cells, in contrast to its well-documented role in the negative regulation of lymphocytes. PMID:17347685

  9. Acute renal infarction from a cardiac thrombus.

    PubMed

    Nasser, Nicola J; Abadi, Sobhi; Azzam, Zaher S

    2007-11-01

    A 53-year-old man presented to hospital 2 hours after the abrupt onset of left upper abdominal pain. He was treated with analgesics and discharged after 4 hours of observation, but presented to another hospital 2 hours later with severe left abdominal pain. His past medical history included ischemic dilated cardiomyopathy due to recurrent myocardial infarction. Physical examination, electrocardiography, laboratory investigations, contrast-enhanced computed tomography, and transesophageal echocardiography. Renal artery thromboembolism resulting from dilated cardiomyopathy, severely reduced cardiac function and an intracardiac thrombus. Anticoagulation with unfractionated heparin followed by enoxaparin and warfarin.

  10. Design and analysis of micro-stirrer for thrombus dissolution

    NASA Astrophysics Data System (ADS)

    Morita, Minoru; Jiang, Zhongwei; Chijimatsu, Naoki

    2007-12-01

    Thrombus or blood clot may cause cerebral infarction and myocardial infarction if the clot can not be dissolved within several hours after it was formed. The objective of this study is to design a new structure of stirrer for thrombus dissolution. In this paper, to stir the solution with a high viscosity like blood, large amplitude was confirmed to be necessary for the stirrer by the fundamental experiment. For this purpose, shape of the stirrer and type of the actuator were changed, and force and displacement of the stirrer were analyzed. Sine waves with the resonance frequencies of the stirrer (50 V; 571 Hz) were used as the input signals. The performance of the stirrer was simulated by Finite Element Analysis (FEA) to obtain large displacement. Results showed that the amplitude at the tip of stirrer was 100 times larger than the output displacement of the PZT actuator stimulated with the resonance frequency. Concluding this paper, a new type of the micro-stirrer was designed and analyzed by FEA and it was found that the proposed stirrer had a large amplitude with a good input voltage efficiency.

  11. Pancreatic neuroendocrine tumor with splenic vein tumor thrombus: A case report.

    PubMed

    Rodriguez, Rodrigo A; Overton, Heidi; Morris, Katherine T

    2014-01-01

    Pancreatic neuroendocrine tumors (PNET) are rare, often indolent malignancies. PNET are classified as functional or nonfunctional based on the secretion of hormones without a negative feedback loop; the latter account for up to 60% of PNET. Although PNET are associated with a better prognosis compared to pancreatic adenocarcinomas, they are often diagnosed in advanced stages, making them a significant source of morbidity for patients. Here we present a rare case of venous tumor thrombus arising from a nonfunctional PNET. A 44-year-old woman was referred for evaluation and treatment of a possible tail of pancreas PNET discovered during work-up for a 9 year history of intermittent subcostal pain. Previous endoscopic ultrasound with fine needle aspiration revealed a 3.5cm×3cm mass, with cytological diagnosis of neuroendocrine tumor. Patient was scheduled for laparoscopic distal pancreatectomy. During surgery the mass was found to encase the splenic vein leading the surgeon to perform an en bloc distal pancreatectomy and splenectomy. Pathologic analysis revealed a 1.8cm×5cm tumor thrombus lodged in the splenic vein. Nonfunctional PNET usually present in advanced stages and can be associated with venous tumor thrombi. Preoperative imaging may not accurately predict the presence of venous tumor thrombi. En bloc resection of primary tumor, involved organs and thrombus is the recommended treatment option and often results in long term survival. New multi-modality strategies are needed for detection of venous involvement in nonfunctional PNET to better assist with preoperative planning and counseling. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Evaluation of accelerated UV and thermal testing for benzene formation in beverages containing benzoate and ascorbic acid.

    PubMed

    Nyman, Patricia J; Wamer, Wayne G; Begley, Timothy H; Diachenko, Gregory W; Perfetti, Gracia A

    2010-04-01

    Under certain conditions, benzene can form in beverages containing benzoic and ascorbic acids. The American Beverage Assn. (ABA) has published guidelines to help manufacturers mitigate benzene formation in beverages. These guidelines recommend accelerated testing conditions to test product formulations, because exposure to ultraviolet (UV) light and elevated temperature over the shelf life of the beverage may result in benzene formation in products containing benzoic and ascorbic acids. In this study, the effects of UVA exposure on benzene formation were determined. Benzene formation was examined for samples contained in UV stabilized and non-UV stabilized packaging. Additionally, the usefulness of accelerated thermal testing to simulate end of shelf-life benzene formation was evaluated for samples containing either benzoic or ascorbic acid, or both. The 24 h studies showed that under intense UVA light benzene levels increased by as much as 53% in model solutions stored in non-UV stabilized bottles, whereas the use of UV stabilized polyethylene terephthalate bottles reduced benzene formation by about 13% relative to the non-UV stabilized bottles. Similar trends were observed for the 7 d study. Retail beverages and positive and negative controls were used to study the accelerated thermal testing conditions. The amount of benzene found in the positive controls and cranberry juice suggests that testing at 40 degrees C for 14 d may more reliably simulate end of shelf-life benzene formation in beverages. Except for cranberry juice, retail beverages were not found to contain detectable amounts of benzene (<0.05 ng/g) at the end of their shelf lives.

  13. Thrombus-in-Transit: A Case for a Multidisciplinary Hospital-Based Pulmonary Embolism System of Care.

    PubMed

    Pappas, Anthony J; Knight, Stephen W; McLean, Katherine Zanyk; Bork, Susan; Kurz, Michael C; Sawyer, Kelly N

    2016-09-01

    Venous thromboembolism, including pulmonary embolism (PE), is a common disease identified in the emergency department that carries significant morbidity and mortality. In its most severe form, PE is fulminant and characterized by cardiac arrest and death. In the midst of risk-stratifying PE by using echocardiography to assess right ventricular function, thrombus-in-transit (free-floating clot in the right atrium or ventricle) may be seen. We present a case of a 49-year-old man diagnosed with an acute saddle PE who was incidentally found to have a thrombus-in-transit and patent foramen ovale and required open thrombectomy. Identification of these additional potentially life-threatening features was possible only due to our availability of risk-stratification resources, specifically bedside echocardiography. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Albeit rare, with a reported incidence estimated at 4%, the presence of thrombus-in-transit may change emergent clinical management. A multidisciplinary team of resources should be considered emergently as part of a hospital-based PE system of care. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Manual Thrombus Aspiration and the Improved Survival of Patients With Unstable Angina Pectoris Treated With Percutaneous Coronary Intervention (30 Months Follow-Up).

    PubMed

    Yildiz, Bekir S; Bilgin, Murat; Zungur, Mustafa; Alihanoglu, Yusuf I; Kilic, Ismail D; Buber, Ipek; Ergin, Ahmet; Kaftan, Havane A; Evrengul, Harun

    2016-02-01

    The clinical effect of intracoronary thrombus aspiration during percutaneous coronary intervention in patients with unstable angina pectoris is unknown. In this study, we aimed to assess how thrombus aspiration during percutaneous coronary intervention affects in-hospital and 30-month mortality and complications in patients with unstable angina pectoris.We undertook an observational cohort study of 645 consecutive unstable angina pectoris patients who had performed percutaneous coronary intervention from February 2011 to March 2013. Before intervention, 159 patients who had culprit lesion with thrombus were randomly assigned to group 1 (thrombus aspiration group) and group 2 (stand-alone percutaneous coronary intervention group). All patients were followed-up 30 months until August 2015.Thrombus aspiration was performed in 64 patients (46%) whose cardiac markers (ie, creatinine kinase [CK-MB] mass and troponin T) were significantly lower after percutaneous coronary intervention than in those of group 2 (CK-MB mass: 3.80 ± 1.11 vs 4.23 ± 0.89, P = 0.012; troponin T: 0.012 ± 0.014 vs 0.018 ± 0.008, P = 0.002). Left ventricular ejection fraction at 6, 12, and 24 months postintervention was significantly higher in the group 1. During a mean follow-up period of 28.87 ± 6.28 months, mortality rates were 6.3% in the group 1 versus 12.9% in the group 2. Thrombus aspiration was also associated with significantly less long-term mortality in unstable angina pectoris patients (adjusted HR: 4.61, 95% CI: 1.16-18.21, P = 0.029).Thrombus aspiration in the context of unstable angina pectoris is associated with a limited elevation in cardiac enzymes during intervention that minimises microembolization and significantly improves both of epicardial flow and myocardial perfusion, as shown by angiographic TIMI flow grade and frame count. Thrombus aspiration during percutaneous coronary intervention in unstable angina pectoris patients has better

  15. Formation of Ultrarelativistic Electron Rings from a Laser-Wakefield Accelerator.

    PubMed

    Pollock, B B; Tsung, F S; Albert, F; Shaw, J L; Clayton, C E; Davidson, A; Lemos, N; Marsh, K A; Pak, A; Ralph, J E; Mori, W B; Joshi, C

    2015-07-31

    Ultrarelativistic-energy electron ring structures have been observed from laser-wakefield acceleration experiments in the blowout regime. These electron rings had 170-280 MeV energies with 5%-25% energy spread and ∼10  pC of charge and were observed over a range of plasma densities and compositions. Three-dimensional particle-in-cell simulations show that laser intensity enhancement in the wake leads to sheath splitting and the formation of a hollow toroidal pocket in the electron density around the wake behind the first wake period. If the laser propagates over a distance greater than the ideal dephasing length, some of the dephasing electrons in the second period can become trapped within the pocket and form an ultrarelativistic electron ring that propagates in free space over a meter-scale distance upon exiting the plasma. Such a structure acts as a relativistic potential well, which has applications for accelerating positively charged particles such as positrons.

  16. Is Thrombus With Subcutaneous Edema Detected by Ultrasonography Related to Short Peripheral Catheter Failure? A Prospective Observational Study.

    PubMed

    Takahashi, Toshiaki; Murayama, Ryoko; Oe, Makoto; Nakagami, Gojiro; Tanabe, Hidenori; Yabunaka, Koichi; Arai, Rika; Komiyama, Chieko; Uchida, Miho; Sanada, Hiromi

    Short peripheral catheter (SPC) failure is an important clinical problem. The purpose of this study was to clarify the relationship between SPC failure and etiologies such as thrombus, subcutaneous edema, and catheter dislodgment using ultrasonography and to explore the risk factors associated with the etiologies. Two hundred catheters that were in use for infusion, excluding chemotherapy, were observed. Risk factors were examined by logistic regression analysis. Sixty catheters were removed as the result of SPC failure. Frequency of thrombus with subcutaneous edema in SPC failure cases was significantly greater than in those cases where therapy was completed without complications (P < .01). Multivariate analysis demonstrated that 2 or more insertion attempts were significantly associated with thrombus with subcutaneous edema. Results suggest that subsurface skin assessment for catheterization could prevent SPC failure.

  17. Size of the thrombus in acute deep vein thrombosis and the significance of patients' age and sex.

    PubMed

    Kierkegaard, A

    1981-01-01

    To determine the significance of patients' age and sex on the size of the thrombus in acute deep vein thrombosis, 420 consecutive phlebograms with acute deep vein thrombosis were studied. A significant correlation between the size of the thrombus and increasing age of the patient as well as the sex of male was noted. It is concluded that older patients and men often are at a high risk of pulmonary embolism at the time of diagnosis.

  18. Current Sheet Formation in a Conical Theta Pinch Faraday Accelerator with Radio-frequency Assisted Discharge

    NASA Technical Reports Server (NTRS)

    Polzin, Kurt A.; Hallock, Ashley K.; Choueiri, Edgar Y.

    2008-01-01

    Data from an inductive conical theta pinch accelerator are presented to gain insight into the process of inductive current sheet formation in the presence of a preionized background gas produced by a steady-state RF-discharge. The presence of a preionized plasma has been previously shown to allow for current sheet formation at lower discharge voltages and energies than those found in other pulsed inductive accelerator concepts, leading to greater accelerator efficiencies at lower power levels. Time-resolved magnetic probe measurements are obtained for different background pressures and pulse energies to characterize the effects of these parameters on current sheet formation. Indices are defined that describe time-resolved current sheet characteristics, such as the total current owing in the current sheet, the time-integrated total current ('strength'), and current sheet velocity. It is found that for a given electric field strength, maximums in total current, strength, and velocity occur for one particular background pressure. At other pressures, these current sheet indices are considerably smaller. The trends observed in these indices are explained in terms of the principles behind Townsend breakdown that lead to a dependence on the ratio of the electric field to the background pressure. Time-integrated photographic data are also obtained at the same experimental conditions, and qualitatively they compare quite favorably with the time-resolved magnetic field data.

  19. Ibrutinib Inhibits Platelet Integrin αIIbβ3 Outside-In Signaling and Thrombus Stability But Not Adhesion to Collagen.

    PubMed

    Bye, Alexander P; Unsworth, Amanda J; Vaiyapuri, Sakthivel; Stainer, Alexander R; Fry, Michael J; Gibbins, Jonathan M

    2015-11-01

    Ibrutinib is an irreversible Bruton tyrosine kinase inhibitor approved for treatment of Waldenstrom macroglobulinemia, chronic lymphocytic leukemia, and mantle cell lymphoma that increases the risk of bleeding among patients. Platelets from ibrutinib-treated patients exhibit deficiencies in collagen-evoked signaling in suspension; however, the significance of this observation and how it relates to bleeding risk is unclear, as platelets encounter immobile collagen in vivo. We sought to clarify the effects of ibrutinib on platelet function to better understand the mechanism underlying bleeding risk. By comparing signaling in suspension and during adhesion to immobilized ligands, we found that the collagen signaling deficiency caused by ibrutinib is milder during adhesion to immobilized collagen. We also found that platelets in whole blood treated with ibrutinib adhered to collagen under arterial shear but formed unstable thrombi, suggesting that the collagen signaling deficiency caused by ibrutinib may not be the predominant cause of bleeding in vivo. However, clot retraction and signaling evoked by platelet adhesion to immobilized fibrinogen were also inhibited by ibrutinib, indicating that integrin αIIbβ3 outside-in signaling is also effected in addition to GPVI signaling. When ibrutinib was combined with the P2Y12 inhibitor, cangrelor, thrombus formation under arterial shear was inhibited additively. These findings suggest that (1) ibrutinib causes GPVI and integrin αIIbβ3 platelet signaling deficiencies that result in formation of unstable thrombi and may contribute toward bleeding observed in vivo and (2) combining ibrutinib with P2Y12 antagonists, which also inhibit thrombus stability, may have a detrimental effect on hemostasis. © 2015 American Heart Association, Inc.

  20. Angiotensin II–accelerated atherosclerosis and aneurysm formation is attenuated in osteopontin-deficient mice

    PubMed Central

    Bruemmer, Dennis; Collins, Alan R.; Noh, Grace; Wang, Wei; Territo, Mary; Arias-Magallona, Sarah; Fishbein, Michael C.; Blaschke, Florian; Kintscher, Ulrich; Graf, Kristof; Law, Ronald E.; Hsueh, Willa A.

    2003-01-01

    Osteopontin (OPN) is expressed in atherosclerotic lesions, particularly in diabetic patients. To determine the role of OPN in atherogenesis, ApoE–/–OPN+/+, ApoE–/–OPN+/–, and ApoE–/–OPN–/– mice were infused with Ang II, inducing vascular OPN expression and accelerating atherosclerosis. Compared with ApoE–/–OPN+/+ mice, ApoE–/–OPN+/– and ApoE–/–OPN–/– mice developed less Ang II–accelerated atherosclerosis. ApoE–/– mice transplanted with bone marrow derived from ApoE–/–OPN–/– mice had less Ang II–induced atherosclerosis compared with animals receiving ApoE–/–OPN+/+ cells. Aortae from Ang II–infused ApoE–/–OPN–/– mice expressed less CD68, C-C-chemokine receptor 2, and VCAM-1. In response to intraperitoneal thioglycollate, recruitment of leukocytes in OPN–/– mice was impaired, and OPN–/– leukocytes exhibited decreased basal and MCP-1–directed migration. Furthermore, macrophage viability in atherosclerotic lesions from Ang II–infused ApoE–/–OPN–/– mice was decreased. Finally, Ang II–induced abdominal aortic aneurysm formation in ApoE–/–OPN–/– mice was reduced and associated with decreased MMP-2 and MMP-9 activity. These data suggest an important role for leukocyte-derived OPN in mediating Ang II–accelerated atherosclerosis and aneurysm formation. PMID:14597759

  1. Pancreatic neuroendocrine tumor with splenic vein tumor thrombus: A case report

    PubMed Central

    Rodriguez, Rodrigo A.; Overton, Heidi; Morris, Katherine T.

    2014-01-01

    INTRODUCTION Pancreatic neuroendocrine tumors (PNET) are rare, often indolent malignancies. PNET are classified as functional or nonfunctional based on the secretion of hormones without a negative feedback loop; the latter account for up to 60% of PNET. Although PNET are associated with a better prognosis compared to pancreatic adenocarcinomas, they are often diagnosed in advanced stages, making them a significant source of morbidity for patients. Here we present a rare case of venous tumor thrombus arising from a nonfunctional PNET. PRESENTATION OF CASE A 44-year-old woman was referred for evaluation and treatment of a possible tail of pancreas PNET discovered during work-up for a 9 year history of intermittent subcostal pain. Previous endoscopic ultrasound with fine needle aspiration revealed a 3.5 cm × 3 cm mass, with cytological diagnosis of neuroendocrine tumor. Patient was scheduled for laparoscopic distal pancreatectomy. During surgery the mass was found to encase the splenic vein leading the surgeon to perform an en bloc distal pancreatectomy and splenectomy. Pathologic analysis revealed a 1.8 cm × 5 cm tumor thrombus lodged in the splenic vein. DISCUSSION Nonfunctional PNET usually present in advanced stages and can be associated with venous tumor thrombi. Preoperative imaging may not accurately predict the presence of venous tumor thrombi. CONCLUSION En bloc resection of primary tumor, involved organs and thrombus is the recommended treatment option and often results in long term survival. New multi-modality strategies are needed for detection of venous involvement in nonfunctional PNET to better assist with preoperative planning and counseling. PMID:25460491

  2. Echocardiographic diagnosis, management and monitoring of pulmonary embolism with right heart thrombus in a patient with myotonic dystrophy: a case report

    PubMed Central

    2010-01-01

    Acute pulmonary embolism (PE) is a common disease which frequently results in life-threatening right ventricular (RV) failure. High-risk PE, presenting with hypotension, shock, RV dysfunction or right heart thrombus is associated with a high mortality, particularly during the first few hours. Accordingly, it is important to commence effective therapy as soon as possible. In the case described in this report, a 49-year-old woman with myotonic dystrophy type 1 presented with acute respiratory failure and hypotension. Transthoracic echocardiography showed signs of right heart failure and a mobile right heart mass highly suspicious of a thrombus. Based on echocardiographic findings, acute thrombolysis was performed resulting in hemodynamic stabilization of the patient and complete resolution of the right heart thrombus. This case underscores the important role of transthoracic echocardiography for the diagnosis, management and monitoring of PE and underlines the efficacy and safety of thrombolysis in the treatment of PE associated with right heart thrombus. PMID:20470437

  3. Swine Model of Thrombotic Caval Occlusion Created by Autologous Thrombus Injection with Assistance of Intra-caval Net Knitting

    PubMed Central

    Shi, Wan-Yin; Wu, Shuang; Hu, Lan-Yue; Liu, Chang-Jian; Gu, Jian-Ping

    2015-01-01

    To evaluate the feasibility of a swine model of thrombotic inferior vena cava (IVC) occlusion (IVCO) created by autologous thrombus injection with assistance of intra-caval net knitting. Sixteen pigs were included and divided into two groups: Group A (n = 10), IVCO model created by knitting a caval net followed by autologous thrombus injection; Group B (n = 6), control model created by knitting a net and normal saline injection. Venography was performed to assess each model and the associated thrombotic occlusion. The vessels were examined histologically to analyse the pathological changes postoperatively. IVCO model was successfully created in 10 animals in Group A (100%). Immediate venography showed extensive clot burden in the IVC. Postoperative venography revealed partial caval occlusion at 7 days, and complete occlusion coupled with collateral vessels at 14 days. Histologically, Group A animals had significantly greater venous wall thickening, with CD163-positive and CD3-positive cell infiltration. Recanalization channels were observed at the margins of the thrombus. By contrast, no thrombotic occlusion of the IVC was observed in Group B. The thrombotic IVCO model can be reliably established in swine. The inflammatory reaction may contribute to the caval thrombus propagation following occlusion. PMID:26680253

  4. Incremental Value of Three-Dimensional Transesophageal Echocardiography over the Two-Dimensional Technique in the Assessment of a Thrombus in Transit through a Patent Foramen Ovale.

    PubMed

    Thind, Munveer; Ahmed, Mustafa I; Gok, Gulay; Joson, Marisa; Elsayed, Mahmoud; Tuck, Benjamin C; Townsley, Matthew M; Klas, Berthold; McGiffin, David C; Nanda, Navin C

    2015-05-01

    We report a case of a right atrial thrombus traversing a patent foramen ovale into the left atrium, where three-dimensional transesophageal echocardiography provided considerable incremental value over two-dimensional transesophageal echocardiography in its assessment. As well as allowing us to better spatially characterize the thrombus, three-dimensional transesophageal echocardiography provided a more quantitative assessment through estimation of total thrombus burden. © 2015, Wiley Periodicals, Inc.

  5. Gigantic Thrombus of the Left Atrium in Mitral Stenosis

    PubMed Central

    Hodzic, Enisa; Granov, Nermir

    2017-01-01

    Introduction Excess dilatation of the left atrium >65 mm is known in the literature as gigantic atrium. This dilation is most commonly encountered in the mitral insufficiency of rheumatic etiology, but also in severe prolapses of the mitral valve, permanent atrial fibrillation, and at the left right shunt with cardiac insufficiency. Case report In this paper is presented a case study of echocardiographically verified giant thrombus in left atrium in a 50 years old female patient aged 50 hospitalized because of tiredness, choking, heartburn and urinary tract symptoms. The patient had rheumatic fever at age of 18 years. At age of 35, she was diagnosed with mitral stenosis. In permanent atrial fibrillation with anamnestic data on the previous cerebrovascular stroke (CVI) and the repeated transitional ischemic seizures. Echocardiographic examination confirmed severe mitral stenosis with moderate aortic insufficiency and gigantic left atrium (LA) with gigantic thrombus. Invasive diagnostics were indicated and performed, followed by an acute cardiac surgery including left atrial thrombectomy and implantation of the mechanical aortic and mitral valve. The surgical course was without complications. Conclusion On eleven postoperative day, after mobilization, the patient experiences stroke with motor aphasia. She was clinically recovering from stroke consequences, and remains cardiollogically stable. PMID:29416208

  6. Characterising the acceleration phase of blast wave formation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fox, T. E., E-mail: tef503@york.ac.uk; Pasley, J.; Central Laser Facility, STFC Rutherford Appleton Laboratory, Harwell Oxford, Didcot OX11 0QX

    2014-10-15

    Intensely heated, localised regions in uniform fluids will rapidly expand and generate an outwardly propagating blast wave. The Sedov-Taylor self-similar solution for such blast waves has long been studied and applied to a variety of scenarios. A characteristic time for their formation has also long been identified using dimensional analysis, which by its very nature, can offer several interpretations. We propose that, rather than simply being a characteristic time, it may be interpreted as the definitive time taken for a blast wave resulting from an intense explosion in a uniform media to contain its maximum kinetic energy. A scaling relationmore » for this measure of the acceleration phase, preceding the establishment of the blast wave, is presented and confirmed using a 1D planar hydrodynamic model.« less

  7. Platelets Drive Thrombus Propagation in a Hematocrit and Glycoprotein VI-Dependent Manner in an In Vitro Venous Thrombosis Model.

    PubMed

    Lehmann, Marcus; Schoeman, Rogier M; Krohl, Patrick J; Wallbank, Alison M; Samaniuk, Joseph R; Jandrot-Perrus, Martine; Neeves, Keith B

    2018-05-01

    The objective of this study was to measure the role of platelets and red blood cells on thrombus propagation in an in vitro model of venous valvular stasis. A microfluidic model with dimensional similarity to human venous valves consists of a sinus distal to a sudden expansion, where for sufficiently high Reynolds numbers, 2 countercurrent vortices arise because of flow separation. The primary vortex is defined by the points of flow separation and reattachment. A secondary vortex forms in the deepest recess of the valve pocket characterized by low shear rates. An initial fibrin gel formed within the secondary vortex of a tissue factor-coated valve sinus. Platelets accumulated at the interface of the fibrin gel and the primary vortex. Red blood cells at physiological hematocrits were necessary to provide an adequate flux of platelets to support thrombus growth out of the valve sinus. A subpopulation of platelets that adhered to fibrin expose phosphatidylserine. Platelet-dependent thrombus growth was attenuated by inhibition of glycoprotein VI with a blocking Fab fragment or D-dimer. A 3-step process regulated by hemodynamics was necessary for robust thrombus propagation: First, immobilized tissue factor initiates coagulation and fibrin deposition within a low flow niche defined by a secondary vortex in the pocket of a model venous valve. Second, a primary vortex delivers platelets to the fibrin interface in a red blood cell-dependent manner. Third, platelets adhere to fibrin, activate through glycoprotein VI, express phosphatidylserine, and subsequently promote thrombus growth beyond the valve sinus and into the bulk flow. © 2018 American Heart Association, Inc.

  8. Accelerated thermokarst formation in the McMurdo Dry Valleys, Antarctica.

    PubMed

    Levy, Joseph S; Fountain, Andrew G; Dickson, James L; Head, James W; Okal, Marianne; Marchant, David R; Watters, Jaclyn

    2013-01-01

    Thermokarst is a land surface lowered and disrupted by melting ground ice. Thermokarst is a major driver of landscape change in the Arctic, but has been considered to be a minor process in Antarctica. Here, we use ground-based and airborne LiDAR coupled with timelapse imaging and meteorological data to show that 1) thermokarst formation has accelerated in Garwood Valley, Antarctica; 2) the rate of thermokarst erosion is presently ~ 10 times the average Holocene rate; and 3) the increased rate of thermokarst formation is driven most strongly by increasing insolation and sediment/albedo feedbacks. This suggests that sediment enhancement of insolation-driven melting may act similarly to expected increases in Antarctic air temperature (presently occurring along the Antarctic Peninsula), and may serve as a leading indicator of imminent landscape change in Antarctica that will generate thermokarst landforms similar to those in Arctic periglacial terrains.

  9. Accelerated thermokarst formation in the McMurdo Dry Valleys, Antarctica

    PubMed Central

    Levy, Joseph S.; Fountain, Andrew G.; Dickson, James L.; Head, James W.; Okal, Marianne; Marchant, David R.; Watters, Jaclyn

    2013-01-01

    Thermokarst is a land surface lowered and disrupted by melting ground ice. Thermokarst is a major driver of landscape change in the Arctic, but has been considered to be a minor process in Antarctica. Here, we use ground-based and airborne LiDAR coupled with timelapse imaging and meteorological data to show that 1) thermokarst formation has accelerated in Garwood Valley, Antarctica; 2) the rate of thermokarst erosion is presently ~ 10 times the average Holocene rate; and 3) the increased rate of thermokarst formation is driven most strongly by increasing insolation and sediment/albedo feedbacks. This suggests that sediment enhancement of insolation-driven melting may act similarly to expected increases in Antarctic air temperature (presently occurring along the Antarctic Peninsula), and may serve as a leading indicator of imminent landscape change in Antarctica that will generate thermokarst landforms similar to those in Arctic periglacial terrains. PMID:23881292

  10. Ultrasound-assisted lysis using recombinant tissue plasminogen activator and the EKOS EkoSonic endovascular system for treating right atrial thrombus and massive pulmonary embolism: A case study.

    PubMed

    Shammas, N W; Padaria, R; Ahuja, G

    2015-12-01

    Right atrial thrombus in the setting of a large pulmonary embolus is rare and is associated with serious adverse events. This case report presents the role played by EKOS EkoSonic ultrasound system in successfully treating right atrial thrombus and massive pulmonary embolism. A 69-year-old female presented with a massive pulmonary embolus and a large mobile right atrial thrombus. She was treated with catheter-directed lysis using the EKOS EkoSonic ultrasound system and tissue plasminogen activator, with complete resolution of her right atrial thrombus and a marked improvement in her pulmonary embolus and hemodynamics. This case report provides a new and an effective option to treat right atrial thrombus associated with a large pulmonary embolus leading to a good outcome. © The Author(s) 2014.

  11. Learner-Responsive Instructional Strategies for Adults in Accelerated Classroom Formats: Creating Inclusive Learning Environments

    ERIC Educational Resources Information Center

    Gupta, Kalpana

    2012-01-01

    This study was focused on investigating inclusive learning environments in accelerated classroom formats. Three 8-week sections of an undergraduate course at Regis University were examined. Results from observations and surveys were analyzed to determine the effectiveness and consistency of 13 inclusive strategies derived from Wlodkowski and…

  12. Optical coherence tomography assessment of efficacy of thrombus aspiration in patients undergoing a primary percutaneous coronary intervention for acute ST-elevation myocardial infarction

    PubMed Central

    Yamaguchi, Tomoyuki; Ino, Yasushi; Matsuo, Yoshiki; Shiono, Yasutsugu; Yamano, Takashi; Taruya, Akira; Nishiguchi, Tsuyoshi; Shimokado, Aiko; Orii, Makoto; Tanaka, Atsushi; Hozumi, Takeshi; Akasaka, Takashi

    2015-01-01

    Objective We used optical coherence tomography (OCT) to assess the impact of thrombus aspiration before angioplasty on poststenting tissue protrusions in patients undergoing a primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). Methods and results A total of 188 patients with STEMI who underwent thrombus-aspiration PCI (n=113) or standard PCI (n=75) were examined in this study. OCT was performed immediately after primary PCI to assess lesion morphology in the stented segment. The minimum stent area was similar between the thrombus-aspiration PCI group and the standard PCI group [7.4 interquartile range (IQR): 5.8–9.4 vs. 7.4 IQR: 5.8–8.9 mm2, P=0.788]. The maximum tissue protrusion area [0.6 (IQR: 0.3–1.1) vs. 1.2 (IQR: 0.8–1.9) mm2, P<0.001], the mean tissue protrusion area [0.1 (IQR: 0.1–0.2) vs. 0.5 (IQR: 0.3–0.8) mm2, P<0.001], and tissue protrusion volume [2.3 (IQR: 1.3–4.3) vs. 8.3 (IQR: 5.4–14.6) mm3, P<0.001] were significantly smaller in the thrombus-aspiration PCI group compared with the standard PCI group. Minimum lumen area was significantly greater in the thrombus-aspiration PCI group compared with the standard PCI group [6.9 (IQR: 5.4–8.8) vs. 6.3 (IQR: 4.6–7.8) mm2, P=0.033]. Conclusion Thrombus aspiration before angioplasty in patients with STEMI was associated with significantly smaller tissue protrusion and larger lumen poststenting compared with standard PCI. Thrombus aspiration in primary PCI favorably influenced lesion morphologies in the stented segment. PMID:26230885

  13. Magnetic resonance venography to assess thrombus resolution with edoxaban monotherapy versus parenteral anticoagulation/warfarin for symptomatic deep vein thrombosis: A multicenter feasibility study.

    PubMed

    Piazza, Gregory; Mani, Venkatesh; Goldhaber, Samuel Z; Grosso, Michael A; Mercuri, Michele; Lanz, Hans J; Schussler, Steven; Hsu, Ching; Chinigo, Amy; Ritchie, Bruce; Nadar, Venkatesh; Cannon, Kevin; Pullman, John; Concha, Mauricio; Schul, Marlin; Fayad, Zahi A

    2016-08-01

    The feasibility of magnetic resonance venography (MRV) for measuring change in thrombus volume with a novel anticoagulation regimen versus standard anticoagulation in patients with symptomatic deep vein thrombosis (DVT) has not been assessed. Our aim was to study the feasibility of MRV to measure change in thrombus volume in patients with acute symptomatic objectively confirmed proximal DVT in an open-label multicenter trial (edoxaban Thrombus Reduction Imaging Study, eTRIS). We randomized patients in a 2:1 allocation ratio to edoxaban 90 mg/day for 10 days followed by 60 mg/day versus parenteral anticoagulation bridging to warfarin for 3 months. The primary efficacy outcome was a surrogate end point of the relative change in MRV-quantified thrombus volume from baseline to Day 14-21. A total of 85 eligible patients from 26 study sites were randomized to edoxaban monotherapy (n=56) versus parenteral anticoagulation as a 'bridge' to warfarin (n=29). The mean relative change in MRV-quantified thrombus volume from baseline to Day 14-21 was similar in patients treated with edoxaban and parenteral anticoagulation as a 'bridge' to warfarin (-50.1% vs -58.9%; 95% confidence interval of treatment difference, -12.7%, 30.2%). However, thrombus extension was observed in eight patients in the edoxaban monotherapy group and in none in the warfarin group. Rates of recurrent venous thromboembolism (3.6% vs 3.6%, p=0.45) and clinically relevant non-major bleeding (5.4% vs 7.1%, p=0.34) were also similar. No major bleeds occurred in either on-treatment group during the study period. In conclusion, MRV can assess change in thrombus volume in patients with acute DVT randomized to two different anticoagulant regimens.ClinicalTrials.gov IDENTIFIER NCT01662908: INVESTIGATIONAL NEW DRUG IND APPLICATION EDOXABAN IND # 63266. © The Author(s) 2016.

  14. Magnetic resonance venography to assess thrombus resolution with edoxaban monotherapy versus parenteral anticoagulation/warfarin for symptomatic deep vein thrombosis: A multicenter feasibility study

    PubMed Central

    Piazza, Gregory; Mani, Venkatesh; Goldhaber, Samuel Z; Grosso, Michael A; Mercuri, Michele; Lanz, Hans J; Schussler, Steven; Hsu, Ching; Chinigo, Amy; Ritchie, Bruce; Nadar, Venkatesh; Cannon, Kevin; Pullman, John; Concha, Mauricio; Schul, Marlin; Fayad, Zahi A

    2016-01-01

    The feasibility of magnetic resonance venography (MRV) for measuring change in thrombus volume with a novel anticoagulation regimen versus standard anticoagulation in patients with symptomatic deep vein thrombosis (DVT) has not been assessed. Our aim was to study the feasibility of MRV to measure change in thrombus volume in patients with acute symptomatic objectively confirmed proximal DVT in an open-label multicenter trial (edoxaban Thrombus Reduction Imaging Study, eTRIS). We randomized patients in a 2:1 allocation ratio to edoxaban 90 mg/day for 10 days followed by 60 mg/day versus parenteral anticoagulation bridging to warfarin for 3 months. The primary efficacy outcome was a surrogate end point of the relative change in MRV-quantified thrombus volume from baseline to Day 14–21. A total of 85 eligible patients from 26 study sites were randomized to edoxaban monotherapy (n=56) versus parenteral anticoagulation as a ‘bridge’ to warfarin (n=29). The mean relative change in MRV-quantified thrombus volume from baseline to Day 14–21 was similar in patients treated with edoxaban and parenteral anticoagulation as a ‘bridge’ to warfarin (−50.1% vs −58.9%; 95% confidence interval of treatment difference, −12.7%, 30.2%). However, thrombus extension was observed in eight patients in the edoxaban monotherapy group and in none in the warfarin group. Rates of recurrent venous thromboembolism (3.6% vs 3.6%, p=0.45) and clinically relevant non-major bleeding (5.4% vs 7.1%, p=0.34) were also similar. No major bleeds occurred in either on-treatment group during the study period. In conclusion, MRV can assess change in thrombus volume in patients with acute DVT randomized to two different anticoagulant regimens. ClinicalTrials.gov Identifier: NCT01662908 Investigational New Drug (IND) Application: Edoxaban IND # 63266 PMID:27165711

  15. Histological Examination of Trousseau Syndrome-Related Thrombus Retrieved Through Acute Endovascular Thrombectomy: Report of 2 Cases.

    PubMed

    Matsumoto, Naoki; Fukuda, Hitoshi; Handa, Akira; Kawasaki, Toshinari; Kurosaki, Yoshitaka; Chin, Masaki; Yamagata, Sen

    2016-12-01

    The mechanism of thrombus formation in Trousseau syndrome remains unclear. The purpose of this study was to investigate specific pathological findings of the thrombi in Trousseau syndrome. The authors report on 2 cases of thrombi in Trousseau syndrome from large cerebral vessels removed by endovascular therapy and compared with thrombi in atherosclerosis or cardiac embolism. The first patient, a 67-year-old man, was transferred to our hospital for sudden onset consciousness disturbance and tetraparesis. He had been diagnosed with stage IV lung cancer. The magnetic resonance (MR) angiography demonstrated basilar artery occlusion. An endovascular thrombectomy was performed. The second patient, an 84-year-old woman, was transferred to our hospital for sudden onset motor aphasia and right-sided motor weakness. She has a history of stage IV pancreatic body cancer. The MR angiography demonstrated left middle cerebral artery occlusion. An endovascular thrombectomy was performed for the floating thrombus. Macroscopic findings of retrieved thrombi were observed immediately after thrombectomy. The thrombi in Trousseau syndrome were white in color and solid against manual compression, whereas thrombi from other causes were red and fragile. In terms of microscopic findings, the thrombi in Trousseau syndrome mainly contained fibrin. On the other hand, thrombi associated with atherosclerosis or cardiac embolism had smaller area of fibrin with a considerable amount of red and white blood cells. The thrombi in Trousseau syndrome, which caused occlusion of large cerebral vessel, almost exclusively consisted of fibrin. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  16. The Influence of Preoperative Aneurysmal Thrombus Quantity and Distribution on the Development of Type II Endoleaks with Aneurysm Sac Enlargement After EVAR of AAA

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Müller-Wille, R., E-mail: rene.mueller-wille@ukr.de; Güntner, O., E-mail: oliverguentner@yahoo.de; Zeman, F., E-mail: florian.zeman@ukr.de

    PurposeTo determine the influence of preoperative aneurysmal thrombus quantity and distribution on the development of type II endoleak with aneurysm sac enlargement after endovascular aneurysm repair (EVAR).Materials and MethodsWe retrospectively analyzed the pre- and postoperatively performed CT scans of 118 patients who had follow-up imaging for at least 1 year after EVAR available. We assessed preoperative thrombus perimeter (T{sub Peri}), diameter (T{sub Dia}), cross-sectional area (T{sub CSA}), and volume (T{sub Vol}). The preoperative thrombus distribution was classified into no thrombus, semilunar-shaped (anterior, right side, left side, posterior) thrombus, and circumferential type thrombus. The number of preoperative patent aortic side branches (ASB)more » was identified. Endpoint was type II endoleak with aneurysm volume (A{sub Vol}) increase of ≥5 % during follow-up.ResultsDuring follow-up (2 years, range 1–9 years), 17 patients with type II endoleak had significant A{sub Vol} increase. Less preoperative T{sub Peri}, T{sub Dia}, T{sub CSA}, and T{sub Vol} were associated with A{sub Vol} increase. A circumferential thrombus distribution significantly protected against aneurysm enlargement (p = 0.028). The variables with the strongest significance for A{sub Vol} increase were preoperative T{sub Vol}/A{sub Vol} ratio (OR 0.95; p = 0.037) and number of patent ASB (OR 3.52; p < 0.001).ConclusionA low preoperative T{sub Vol}/A{sub Vol} ratio and a high number of patent ASB were associated with aneurysm sac enlargement after EVAR.« less

  17. Thrombus Degradation by Fibrinolytic Enzyme of Stenotrophomonas sp. Originated from Indonesian Soybean-Based Fermented Food on Wistar Rats

    PubMed Central

    Tjandrawinata, Raymond R.

    2016-01-01

    Objective. To evaluate thrombus degrading effect of a fibrinolytic enzyme from food origin Stenotrophomonas sp. of Indonesia. Methods. Prior to animal study, the enzyme safety was tested using cell culture. The effect on expression of tissue plasminogen activator was also analysed in the cell culture. For in vivo studies, 25 Wistar rats were used: normal control, negative control, treatment groups with crude and semipurified enzyme given orally at 25 mg/kg, and positive control group which received Lumbrokinase at 25 mg/kg. Blood clot in the tail was induced by kappa carrageenan injection at 1 mg/kg BW. Results. Experiment with cell culture confirmed the enzyme safety at the concentration used and increased expression of tPA. Decreasing of thrombus was observed in the positive group down to 70.35 ± 23.11% of the negative control animals (100%). The thrombus observed in the crude enzyme treatment was down to 56.99 ± 15.95% and 71.5 ± 15.7% for semipurified enzyme. Scanning electron microscopy showed clearly that bood clots were found in the animals injected with kappa carrageenan; however, in the treatment and positive groups, the clot was much reduced. Conclusions. Oral treatment of enzyme from Stenotrophomonas sp. of Indonesian fermented food was capable of degrading thrombus induced in Wistar rats. PMID:27635131

  18. Thrombophilia-Related Complications in the Treatment of a Left Atrial Appendage Thrombus: A Case Report

    PubMed Central

    Parato, Vito Maurizio; Scarano, Michele; Labanti, Benedetto

    2014-01-01

    Trans-esophageal echocardiography (TEE) revealed a left atrial appendage (LAA) thrombus in an 84-year-old woman with nonvalvular atrial fibrillation not known before our evaluation. In her medical history, there were hypertension, dyslipidemia and a previous pulmonary embolism. She was taking warfarin at time of our evaluation and presented signs and symptoms of heart failure. Together with heart failure treatment, intravenous anticoagulation with unfractionated heparin was initiated. Treatment was complicated by additional right lower limb embolic event and the LAA thrombus remained unchanged. Testing revealed heterozygosity for both the factor V Leiden and the methylenetetrahydrofolate reductase C677T mutations inducing resistance to activated protein C. The patient refused transcatheter closure of the left atrial appendage. PMID:28465906

  19. Stent-thrombus interaction and the influence of aspiration on mechanical thrombectomy: evaluation of different stent retrievers in a circulation model.

    PubMed

    Madjidyar, Jawid; Hermes, Julian; Freitag-Wolf, Sandra; Jansen, Olav

    2015-08-01

    Different devices and techniques are available for endovascular treatment of ischemic stroke. In this in vitro study, we examined the stent-thrombus interaction and the influence of additional aspiration on the efficiency of mechanical thrombectomy with established stent retrievers. Human blood thrombi were made in a Chandler loop. The thrombi were placed into the middle cerebral artery of a vascular silicon phantom. A programmable piston pump was used to acquire physiological flow in the model. Resistances were interposed to gain physiological pressure. The stent retrievers Trevo, Solitaire FR, Separator 3D, and Aperio were used to perform thrombectomy under direct visual control. For the additional aspiration, we used intermediate catheters. Ten attempts per device were made with and without aspiration under standardized conditions, a total of n = 80. For all thrombectomy maneuvers, it was demonstrated that the thrombus was pushed by the stent struts against the vessel wall and was retracted along it. The stent-thrombus interaction was only superficial for all devices. Using additional distal aspiration, the amount of distal embolism and rate of embolism in new territories was significantly lower than without. Moreover, additional aspiration reduced the number of recanalization maneuvers and the recanalization time. Distal aspiration with intermediate catheters increases the efficacy of mechanical thrombectomy with stent retrievers significantly. In contrary to earlier suggestions, the interaction between the thrombus and the stent retriever is only superficial, rather than an integration of the thrombus into the retriever. No significant differences between the proven devices could be shown in our model.

  20. Intermittent, noncyclic dysfunction of a mechanical aortic prosthesis by pannus formation.

    PubMed

    Giroux, Sylvie K; Labinaz, Marino X; Grisoli, Dominique; Klug, Andrew P; Veinot, John P; Burwash, Ian G

    2010-01-01

    Mechanical aortic prosthesis dysfunction can result from thrombosis or pannus formation. Pannus formation usually restricts systolic excursion of the occluding disk, resulting in progressive stenosis of the aortic prosthesis. Intermittent dysfunction of a mechanical aortic prosthesis is usually ascribed to thrombus formation. We describe an unusual case of intermittent, noncyclic dysfunction of a mechanical aortic prosthesis due to pannus formation in the absence of systolic restriction of disk excursion that presented with intermittent massive aortic regurgitation, severe ischemia, and shock. Pannus formation should be considered as a potential cause of acute intermittent severe aortic regurgitation in a patient with a mechanical aortic prosthesis.

  1. Thrombus Burden of Deep Vein Thrombosis and Its Association with Thromboprophylaxis and D-Dimer Measurement: Insights from the APEX Trial.

    PubMed

    Chi, Gerald; Goldhaber, Samuel Z; Hull, Russell D; Hernandez, Adrian F; Kerneis, Mathieu; Al Khalfan, Fahad; Cohen, Alexander T; Harrington, Robert A; Gibson, C Michael

    2017-12-01

    Background The aim of this study was to evaluate the effect of betrixaban on the occurrence of deep vein thrombosis (DVT) and also the extent of thrombus and to assess the association of baseline D-dimer with subsequent thrombus burden. Methods In the APEX trial (ClinicalTrials.gov: NCT01583218), 7,513 acutely ill hospitalized medical patients were randomly assigned to extended-duration betrixaban (35–42 days) or enoxaparin (10 ± 4 days). D-dimer concentration was measured at baseline, and mandatory lower-extremity compression ultrasonography (CUS) was performed at 35 to 42 days. The thrombus burden of DVT was assessed by the number of non-compressible vascular segments in six target proximal veins and compared between treatment groups and D-dimer categories (≥2 × upper limit of normal [ULN] versus <2 × ULN). Results Compared with enoxaparin, extended-duration betrixaban reduced the DVT risk at 35 to 42 days (any-dose: relative risk [RR] = 0.76 [95% confidence interval: 0.61–0.94]; p = 0.013; full-dose: RR = 0.70 [0.55–0.90]; p = 0.005). Patients who received betrixaban were more likely to have a lower thrombus burden (p = 0.012 for any-dose and p = 0.001 for full-dose). Elevated D-dimer at baseline was independently associated with a 2.12-fold increased risk of developing DVT (p < 0.001). A greater thrombus burden was also observed in those with D-dimer ≥ 2 × ULN compared with <2 × ULN (p < 0.0001). Conclusion Extended-duration betrixaban reduced the number of venous segments with thrombosis at 35 to 42 days compared with enoxaparin. A positive D-dimer was associated with a greater extent of thrombus burden among acutely ill medical patients who developed DVT despite receiving thromboprophylaxis.

  2. Angiographic and Clinical Impact of Successful Manual Thrombus Aspiration in Diabetic Patients Undergoing Primary PCI

    PubMed Central

    2014-01-01

    Background. Diabetes mellitus is associated with worse angiographic and clinical outcomes after percutaneous coronary intervention (PCI). Aim. To investigate the impact of manual thrombus aspiration on in-stent restenosis (ISR) and clinical outcome in patients treated by bare-metal stent (BMS) implantation for ST-segment elevation myocardial infarction (STEMI). Methods. 100 diabetic patients were prospectively enrolled. They were randomly assigned to undergo either standard primary PCI (group A, 50 patients) or PCI with thrombus aspiration using Export catheter (group B, 50 patients). The primary endpoint was the rate of eight-month ISR. The secondary endpoint included follow-up for major adverse cardiac events (MACE). Results. Mean age of the study cohort was 59.86 ± 8.3 years, with 64 (64%) being males. Baseline characteristics did not differ between both groups. Eight-month angiogram showed that group B patients had significantly less late lumen loss (0.17 ± 0.35 versus 0.60 ± 0.42 mm, P < 0.001), with lower incidence of ISR (4% versus 16.6%, P < 0.001). There was a trend towards lower rate of MACE in the same group of patients. Conclusion. In diabetic patients undergoing primary PCI, manual thrombus aspiration (compared with standard PCI) was associated with better ISR rate after BMS implantation. PMID:24804102

  3. Accelerated gravity testing of aquitard core permeability and implications at formation and regional scale

    NASA Astrophysics Data System (ADS)

    Timms, W. A.; Crane, R.; Anderson, D. J.; Bouzalakos, S.; Whelan, M.; McGeeney, D.; Rahman, P. F.; Guinea, A.; Acworth, R. I.

    2015-03-01

    Evaluating the possibility of leakage through low permeability geological strata is critically important for sustainable water supplies, the extraction of fuels from strata such as coal beds, and the confinement of waste within the earth. The current work demonstrates that relatively rapid and reliable hydraulic conductivity (K) measurement of aquitard cores using accelerated gravity can inform and constrain larger scale assessments of hydraulic connectivity. Steady state fluid velocity through a low K porous sample is linearly related to accelerated gravity (g-level) in a centrifuge permeameter (CP) unless consolidation or geochemical reactions occur. The CP module was custom designed to fit a standard 2 m diameter geotechnical centrifuge (550 g maximum) with a capacity for sample dimensions of 30 to 100 mm diameter and 30 to 200 mm in length, and a maximum total stress of ~2 MPa at the base of the core. Formation fluids were used as influent to limit any shrink-swell phenomena which may alter the permeability. Vertical hydraulic conductivity (Kv) results from CP testing of cores from three sites within the same regional clayey silt formation varied (10-7 to 10-9 m s-1, n = 14). Results at one of these sites (1.1 × 10-10 to 3.5 × 10-9 m s-1, n = 5) that were obtained in < 24 h were similar to in situ Kv values (3 × 10-9 m s-1) from pore pressure responses over several weeks within a 30 m clayey sequence. Core scale and in situ Kv results were compared with vertical connectivity within a regional flow model, and considered in the context of heterogeneity and preferential flow paths at site and formation scale. More reliable assessments of leakage and solute transport though aquitards over multi-decadal timescales can be achieved by accelerated core testing together with advanced geostatistical and numerical methods.

  4. Time-dependent Electron Acceleration in Blazar Transients: X-Ray Time Lags and Spectral Formation

    NASA Astrophysics Data System (ADS)

    Lewis, Tiffany R.; Becker, Peter A.; Finke, Justin D.

    2016-06-01

    Electromagnetic radiation from blazar jets often displays strong variability, extending from radio to γ-ray frequencies. In a few cases, this variability has been characterized using Fourier time lags, such as those detected in the X-rays from Mrk 421 using BeppoSAX. The lack of a theoretical framework to interpret the data has motivated us to develop a new model for the formation of the X-ray spectrum and the time lags in blazar jets based on a transport equation including terms describing stochastic Fermi acceleration, synchrotron losses, shock acceleration, adiabatic expansion, and spatial diffusion. We derive the exact solution for the Fourier transform of the electron distribution and use it to compute the Fourier transform of the synchrotron radiation spectrum and the associated X-ray time lags. The same theoretical framework is also used to compute the peak flare X-ray spectrum, assuming that a steady-state electron distribution is achieved during the peak of the flare. The model parameters are constrained by comparing the theoretical predictions with the observational data for Mrk 421. The resulting integrated model yields, for the first time, a complete first-principles physical explanation for both the formation of the observed time lags and the shape of the peak flare X-ray spectrum. It also yields direct estimates of the strength of the shock and the stochastic magnetohydrodynamical wave acceleration components in the Mrk 421 jet.

  5. Benzalkonium chloride accelerates the formation of the amyloid fibrils of corneal dystrophy-associated peptides.

    PubMed

    Kato, Yusuke; Yagi, Hisashi; Kaji, Yuichi; Oshika, Tetsuro; Goto, Yuji

    2013-08-30

    Corneal dystrophies are genetic disorders resulting in progressive corneal clouding due to the deposition of amyloid fibrils derived from keratoepithelin, also called transforming growth factor β-induced protein (TGFBI). The formation of amyloid fibrils is often accelerated by surfactants such as sodium dodecyl sulfate (SDS). Most eye drops contain benzalkonium chloride (BAC), a cationic surfactant, as a preservative substance. In the present study, we aimed to reveal the role of BAC in the amyloid fibrillation of keratoepithelin-derived peptides in vitro. We used three types of 22-residue synthetic peptides covering Leu110-Glu131 of the keratoepithelin sequence: an R-type peptide with wild-type R124, a C-type peptide with C124 associated with lattice corneal dystrophy type I, and a H-type peptide with H124 associated with granular corneal dystrophy type II. The time courses of spontaneous amyloid fibrillation and seed-dependent fibril elongation were monitored in the presence of various concentrations of BAC or SDS using thioflavin T fluorescence. BAC and SDS accelerated the fibrillation of all synthetic peptides in the absence and presence of seeds. Optimal acceleration occurred near the CMC, which suggests that the unstable and dynamic interactions of keratoepithelin peptides with amphipathic surfactants led to the formation of fibrils. These results suggest that eye drops containing BAC may deteriorate corneal dystrophies and that those without BAC are preferred especially for patients with corneal dystrophies.

  6. Benzalkonium Chloride Accelerates the Formation of the Amyloid Fibrils of Corneal Dystrophy-associated Peptides*

    PubMed Central

    Kato, Yusuke; Yagi, Hisashi; Kaji, Yuichi; Oshika, Tetsuro; Goto, Yuji

    2013-01-01

    Corneal dystrophies are genetic disorders resulting in progressive corneal clouding due to the deposition of amyloid fibrils derived from keratoepithelin, also called transforming growth factor β-induced protein (TGFBI). The formation of amyloid fibrils is often accelerated by surfactants such as sodium dodecyl sulfate (SDS). Most eye drops contain benzalkonium chloride (BAC), a cationic surfactant, as a preservative substance. In the present study, we aimed to reveal the role of BAC in the amyloid fibrillation of keratoepithelin-derived peptides in vitro. We used three types of 22-residue synthetic peptides covering Leu110-Glu131 of the keratoepithelin sequence: an R-type peptide with wild-type R124, a C-type peptide with C124 associated with lattice corneal dystrophy type I, and a H-type peptide with H124 associated with granular corneal dystrophy type II. The time courses of spontaneous amyloid fibrillation and seed-dependent fibril elongation were monitored in the presence of various concentrations of BAC or SDS using thioflavin T fluorescence. BAC and SDS accelerated the fibrillation of all synthetic peptides in the absence and presence of seeds. Optimal acceleration occurred near the CMC, which suggests that the unstable and dynamic interactions of keratoepithelin peptides with amphipathic surfactants led to the formation of fibrils. These results suggest that eye drops containing BAC may deteriorate corneal dystrophies and that those without BAC are preferred especially for patients with corneal dystrophies. PMID:23861389

  7. TIME-DEPENDENT ELECTRON ACCELERATION IN BLAZAR TRANSIENTS: X-RAY TIME LAGS AND SPECTRAL FORMATION

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lewis, Tiffany R.; Becker, Peter A.; Finke, Justin D., E-mail: pbecker@gmu.edu, E-mail: tlewis13@gmu.edu, E-mail: justin.finke@nrl.navy.mil

    2016-06-20

    Electromagnetic radiation from blazar jets often displays strong variability, extending from radio to γ -ray frequencies. In a few cases, this variability has been characterized using Fourier time lags, such as those detected in the X-rays from Mrk 421 using Beppo SAX. The lack of a theoretical framework to interpret the data has motivated us to develop a new model for the formation of the X-ray spectrum and the time lags in blazar jets based on a transport equation including terms describing stochastic Fermi acceleration, synchrotron losses, shock acceleration, adiabatic expansion, and spatial diffusion. We derive the exact solution formore » the Fourier transform of the electron distribution and use it to compute the Fourier transform of the synchrotron radiation spectrum and the associated X-ray time lags. The same theoretical framework is also used to compute the peak flare X-ray spectrum, assuming that a steady-state electron distribution is achieved during the peak of the flare. The model parameters are constrained by comparing the theoretical predictions with the observational data for Mrk 421. The resulting integrated model yields, for the first time, a complete first-principles physical explanation for both the formation of the observed time lags and the shape of the peak flare X-ray spectrum. It also yields direct estimates of the strength of the shock and the stochastic magnetohydrodynamical wave acceleration components in the Mrk 421 jet.« less

  8. Plasminogen associates with phosphatidylserine-exposing platelets and contributes to thrombus lysis under flow

    PubMed Central

    Whyte, Claire S.; Swieringa, Frauke; Mastenbroek, Tom G.; Lionikiene, Ausra S.; Lancé, Marcus D.; van der Meijden, Paola E. J.; Heemskerk, Johan W. M.

    2015-01-01

    The interaction of plasminogen with platelets and their localization during thrombus formation and fibrinolysis under flow are not defined. Using a novel model of whole blood thrombi, formed under flow, we examine dose-dependent fibrinolysis using fluorescence microscopy. Fibrinolysis was dependent upon flow and the balance between fibrin formation and plasminogen activation, with tissue plasminogen activator-mediated lysis being more efficient than urokinase plasminogen activator-mediated lysis. Fluorescently labeled plasminogen radiates from platelet aggregates at the base of thrombi, primarily in association with fibrin. Hirudin attenuates, but does not abolish plasminogen binding, denoting the importance of fibrin. Flow cytometry revealed that stimulation of platelets with thrombin/convulxin significantly increased the plasminogen signal associated with phosphatidylserine (PS)-exposing platelets. Binding was attenuated by tirofiban and Gly-Pro-Arg-Pro amide, confirming a role for fibrin in amplifying plasminogen binding to PS-exposing platelets. Confocal microscopy revealed direct binding of plasminogen and fibrinogen to different platelet subpopulations. Binding of plasminogen and fibrinogen co-localized with PAC-1 in the center of spread platelets. In contrast, PS-exposing platelets were PAC-1 negative, and bound plasminogen and fibrinogen in a protruding “cap.” These data show that different subpopulations of platelets harbor plasminogen by diverse mechanisms and provide an essential scaffold for the accumulation of fibrinolytic proteins that mediate fibrinolysis under flow. PMID:25712989

  9. A novel approach for assessing the progression of deep venous thrombosis by area of venous thrombus in ultrasonic elastography.

    PubMed

    Wang, Chao; Wang, Lei; Zhang, Yuhui; Chen, Ming

    2014-04-01

    Exact age determination of deep venous thrombosis (DVT) is important for an appropriate treatment. The purpose of this present study is to assess the age of acute DVT with the area of venous thrombi in elasticity imaging during the thrombosis procession. The thrombus area is obtained from a specially designed program. It was applied to clot specimens induced in human great saphenous (n = 15) at selected time points following the initiation of thrombosis. The relative mean proportion of blood clots was 50.01% ± 12.44% at day 1; 69.94% ± 8.19% at day 3; 81.93% ± 6.15% at day 6; and 92.37% ± 4.06% at day 9. The results indicated that the thrombus area increased significantly over time, while the normalized strain values inside the thrombus changed only a little. The pathological analyses also showed the same results. Therefore, we conclude that the area of venous thrombi in elasticity imaging may be a novel function for acute DVT staging.

  10. Intravascular ultrasound and angiographic demonstration of left main stem thrombus-high-risk presentation in a young adult with anabolic steroid abuse.

    PubMed

    Garg, Pankaj; Davis, Gershan; Wilson, John Ian; Sivananthan, Mohan

    2010-01-01

    We present a case of acute myocardial infarction in a young adult with a history of anabolic steroid abuse. On diagnostic coronary angiography and intravascular ultrasound, he was found to have a distal left main stem thrombus extending into the proximal left anterior descending artery and a large intermediate vessel. As he was hemodynamically stable and pain-free, he was managed conservatively with triple antiplatelet therapy (aspirin, clopidogrel, and abciximab). This was also to avoid the risk of 'wiring the vessel,' especially if there was underlying dissection. Repeat angiography a few weeks later showed complete thrombus resolution. This is the first reported case of extensive left main stem thrombus in a young patient with anabolic steroid abuse. Management of such cases is not straightforward and our case highlights one approach to both diagnosis and treatment.

  11. Left Ventricular Thrombus as a Complication of Clozapine-Induced Cardiomyopathy: A Case Report and Brief Literature Review.

    PubMed

    Malik, Shahbaz A; Malik, Sarah; Dowsley, Taylor F; Singh, Balwinder

    2015-01-01

    A 48-year-old male with history of schizoaffective disorder on clozapine presented with chest pain, dyspnea, and new left bundle branch block. He underwent coronary angiography, which revealed no atherosclerosis. The patient's workup was unrevealing for a cause for the cardiomyopathy and thus it was thought that clozapine was the offending agent. The patient was taken off clozapine and started on guideline directed heart failure therapy. During the course of hospitalization, he was also discovered to have a left ventricular (LV) thrombus for which he received anticoagulation. To our knowledge, this is the first case report of clozapine-induced cardiomyopathy complicated by a LV thrombus.

  12. Satellite RNA Increases DNA Damage and Accelerates Tumor Formation in Mouse Models of Pancreatic Cancer.

    PubMed

    Kishikawa, Takahiro; Otsuka, Motoyuki; Suzuki, Tatsunori; Seimiya, Takahiro; Sekiba, Kazuma; Ishibashi, Rei; Tanaka, Eri; Ohno, Motoko; Yamagami, Mari; Koike, Kazuhiko

    2018-05-10

    Highly repetitive tandem arrays such as satellite sequences in the centromeric and pericentromeric regions of chromosomes, which were previously considered to be silent, are actively transcribed in various biological processes, including cancers. In the pancreas, this aberrant expression occurs even in Kras-mutated pancreatic intraepithelial neoplasia (PanIN) tissues, which are precancerous lesions. To determine the biological role of satellite RNAs in carcinogenesis in vivo , we constructed mouse major satellite (MajSAT) RNA-expressing transgenic mice. However, these transgenic mice did not show spontaneous malignant tumor formation under normal breeding. Importantly, however, DNA damage was increased in pancreatic tissues induced by caerulein treatment or high-fat diet, which may be due to impaired nuclear localization of Y-Box Binding Protein 1 (YBX1), a component of the DNA damage repair machinery. In addition, when crossed with pancreas-specific Kras-mutant mice, MajSAT RNA expression resulted in an earlier increase in PanIN formation. These results suggest that aberrant MajSAT RNA expression accelerates oncogenesis by increasing the probability of a second driver mutation, thus accelerating cells to exit from the breakthrough phase to the expansion phase. Implications: Aberrant expression of satellite RNAs accelerates oncogenesis through a mechanism involving increased DNA damage. Mol Cancer Res; 1-8. ©2018 AACR. ©2018 American Association for Cancer Research.

  13. Imaging of pannus formation in patients with mechanical heart valves.

    PubMed

    Gündüz, Sabahattin; Özkan, Mehmet; Yesin, Mahmut

    2015-11-26

    Patient-prosthesis mismatch (PPM) should be recognized in patients with elevated transprosthetic gradients but without leaflet immobility, since the treatment strategy may differ in either etiology. However, thrombus and/or pannus formation should be excluded before a diagnosis of PPM is made. Particularly, pannus formation may not be diagnosed with 2-dimensional transesophageal echocardiography. Electrocardiographically gated 64-section multidetector computed tomography (MDCT) may be a promising tool in diagnosing or excluding pannus formation. Our report underlines the utility of MDCT in this regard and also emphasizes the importance of recognition of PPM as a differential diagnosis in such patients.

  14. Imaging of pannus formation in patients with mechanical heart valves

    PubMed Central

    Gündüz, Sabahattin; Özkan, Mehmet; Yesin, Mahmut

    2015-01-01

    Patient-prosthesis mismatch (PPM) should be recognized in patients with elevated transprosthetic gradients but without leaflet immobility, since the treatment strategy may differ in either etiology. However, thrombus and/or pannus formation should be excluded before a diagnosis of PPM is made. Particularly, pannus formation may not be diagnosed with 2-dimensional transesophageal echocardiography. Electrocardiographically gated 64-section multidetector computed tomography (MDCT) may be a promising tool in diagnosing or excluding pannus formation. Our report underlines the utility of MDCT in this regard and also emphasizes the importance of recognition of PPM as a differential diagnosis in such patients. PMID:26635931

  15. Surgical resection of recurrent extrahepatic hepatocellular carcinoma with tumor thrombus extending into the right atrium under cardiopulmonary bypass: a case report and review of the literature.

    PubMed

    Ohta, Mineto; Nakanishi, Chikashi; Kawagishi, Naoki; Hara, Yasuyuki; Maida, Kai; Kashiwadate, Toshiaki; Miyazawa, Koji; Yoshida, Satoru; Miyagi, Shigehito; Hayatsu, Yukihiro; Kawamoto, Shunsuke; Matsuda, Yasushi; Okada, Yoshinori; Saiki, Yoshikatsu; Ohuchi, Noriaki

    2016-12-01

    Recurrent hepatocellular carcinoma accompanied by a right atrial tumor thrombus is rare. No standard treatment modality has been established. Surgical treatment may be the only curative treatment; however, surgery has been considered high risk. We herein describe a patient who underwent resection of a recurrent right atrial tumor thrombus under normothermic cardiopulmonary bypass on a beating heart. A 60-year-old man underwent a right hepatectomy for hepatocellular carcinoma with diaphragm invasion. During the preoperative cardiac screening, he was diagnosed with an old myocardial infarction with triple-vessel coronary disease. Percutaneous coronary intervention was performed for the left anterior descending artery and left circumflex coronary artery. High-grade stenosis remained in his right coronary artery. Nine months later, computed tomography showed recurrent hepatocellular carcinoma in the diaphragm and a tumor thrombus extending from the suprahepatic inferior vena cava into the right atrium. Surgical resection of the recurrent tumor was performed through a right subcostal incision with xiphoid extension and median sternotomy. The recurrent tumor was incised with the diaphragm and pericardium. Intraoperative ultrasonography revealed that the tumor thrombus was free from right atrium wall invasion and that the right atrium could be clamped just proximal to the tumor thrombus. The right atrium, infrahepatic vena cava, left and middle hepatic veins, and hepatoduodenal ligament were encircled. Cardiopulmonary bypass was performed to prevent ischemic heart disease caused by intraoperative hypotension. Total hepatic vascular exclusion was then performed under normothermic cardiopulmonary bypass on heart beating. The inferior vena cava wall was incised. The tumor thrombus with the diaphragmatic recurrent tumor was resected en bloc. The patient had a favorable clinical course without any complications. The recurrent hepatocellular carcinoma in the diaphragm and the

  16. LANDSAT-D accelerated payload correction subsystem output computer compatible tape format

    NASA Technical Reports Server (NTRS)

    1982-01-01

    The NASA GSFC LANDSAT-D Ground Segment (GS) is developing an Accelerated Payload Correction Subsystem (APCS) to provide Thematic Mapper (TM) image correction data to be used outside the GS. This correction data is computed from a subset of the TM Payload Correction Data (PCD), which is downlinked from the spacecraft in a 32 Kbps data stream, and mirror scan correction data (MSCD), which is extracted from the wideband video data. This correction data is generated in the GS Thematic Mapper Mission Management Facility (MMF-T), and is recorded on a 9-track 1600 bit per inch computer compatible tape (CCT). This CCT is known as a APCS Output CCT (AOT). The AOT follows standardized corrections with respect to data formats, record construction and record identification. Applicable documents are delineated; common conventions which are used in further defining the structure, format and content of the AOT are defined; and the structure and content of the AOT are described.

  17. The role of three-dimensional imaging in optimizing diagnosis, classification and surgical treatment of hepatocellular carcinoma with portal vein tumor thrombus.

    PubMed

    Wei, Xu-Biao; Xu, Jie; Li, Nan; Yu, Ying; Shi, Jie; Guo, Wei-Xing; Cheng, Hong-Yan; Wu, Meng-Chao; Lau, Wan-Yee; Cheng, Shu-Qun

    2016-03-01

    Accurate assessment of characteristics of tumor and portal vein tumor thrombus is crucial in the management of hepatocellular carcinoma. Comparison of the three-dimensional imaging with multiple-slice computed tomography in the diagnosis and treatment of hepatocellular carcinoma with portal vein tumor thrombus. Patients eligible for surgical resection were divided into the three-dimensional imaging group or the multiple-slice computed tomography group according to the type of preoperative assessment. The clinical data were collected and compared. 74 patients were enrolled into this study. The weighted κ values for comparison between the thrombus type based on preoperative evaluation and intraoperative findings were 0.87 for the three-dimensional reconstruction group (n = 31) and 0.78 for the control group (n = 43). Three-dimensional reconstruction was significantly associated with a higher rate of en-bloc resection of tumor and thrombus (P = 0.025). Using three-dimensional reconstruction, significant correlation existed between the predicted and actual volumes of the resected specimens (r = 0.82, P < 0.01), as well as the predicted and actual resection margins (r = 0.97, P < 0.01). Preoperative three-dimensional reconstruction significantly decreased tumor recurrence and tumor-related death, with hazard ratios of 0.49 (95% confidential interval, 0.27-0.90) and 0.41 (95% confidential interval, 0.21-0.78), respectively. For hepatocellular carcinoma with portal vein tumor thrombus, three-dimensional imaging was efficient in facilitating surgical treatment and benefiting postoperative survivals. Copyright © 2015 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

  18. Synergistic effect of signaling from receptors of soluble platelet agonists and outside-in signaling in formation of a stable fibrinogen-integrin αIIbβ3-actin cytoskeleton complex.

    PubMed

    Budnik, Ivan; Shenkman, Boris; Savion, Naphtali

    2015-01-01

    Thrombus formation in the injured vessel wall is a highly complex process involving various blood-born components that go through specific temporal and spatial changes as observed by intravital videomicroscopy. Platelets bind transiently to the developing thrombus and may either become stably incorporated into or disengage from the thrombus. The aim of the present study was to reveal the processes involved in the formation of a stable thrombus. Platelet-rich plasma and washed platelets were studied by the aggregometer. The aggregate stability was challenged by eptifibatide. Platelet Triton-insoluble fraction was prepared and the actin and αIIb content in the cytoskeleton was analyzed by western blot. Maximal actin polymerization is achieved 1min after platelet activation while maximal αIIbβ3-actin cytoskeleton association requires 5 to 10min of activation and fibrinogen-mediated platelet-to-platelet bridging. Thus, actin polymerization is dependent on platelet activation and requires neither αIIbβ3 integrin occupation nor platelet aggregation. Formation of a stable aggregate requires platelet activation for more than 1min, complete increase in actin cytoskeleton fraction and partial association of αIIbβ3 with the actin cytoskeleton. However, direct αIIbβ3 activation is not sufficient for cytoskeleton complex formation. Thus, stable αIIbβ3-fibrinogen interaction, representing stable aggregate, is achieved after more than 1min agonist activation, involving inside-out and outside-in signaling but not after direct integrin activation, involving only outside-in signaling. Formation of a stable fibrinogen-αIIbβ3-actin cytoskeleton complex is the result of the combined effect of platelet stimulation by soluble agonists, activation of αIIbβ3, fibrinogen binding and platelet-to-platelet bridging. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Accelerated healing of cardiovascular textiles promoted by an RGD peptide.

    PubMed

    Tweden, K S; Harasaki, H; Jones, M; Blevitt, J M; Craig, W S; Pierschbacher, M; Helmus, M N

    1995-07-01

    Polytetrafluoroethylene (PTFE) and polyethylene terephthalate (Dacron polyester) fabrics are used extensively in cardiovascular devices, e.g. heart valve sewing cuffs and vascular prostheses. While devices containing these fabrics are generally successful, it is recognized that fabrics cause complications prior to tissue ingrowth due to their thrombogenic nature. A surface active synthetic peptide, called PepTite Coating (PepTite), which was modeled after the cell attachment domain of human fibronectin has been marketed as a biocompatible coating. This peptide stimulates cell attachment through the arginine-glycine-aspartic acid (RGD) sequence. Modification of medical implants with PepTite has been shown to promote ingrowth of surrounding cells into the material leading to better tissue integration, reduced inflammation and reduced fibrotic encapsulation. In this study, polyester and PTFE textiles were modified with PepTite. The effectiveness of this coating in enhancing wound healing was investigated in a simple vascular and cardiac valve model. Our results indicate that the RGD-containing peptide, PepTite, promoted the formation of an endothelial-like cell layer on both polyester and PTFE vascular patches in the dog model. PepTite was also found to promote the formation of a significantly thinner neointima (pannus) on polyester as compared to that on its uncoated control. These results were corroborated in the cardiac valve model in which a greater amount of thin pannus and less thrombus were seen on coated polyester sewing cuffs than on control uncoated cuffs. This research shows the promising tissue response to RGD coated textiles and the potential role of this peptide in material passivation via accelerated healing.

  20. Concurrent renal amyloidosis and thymoma resulting in a fatal ventricular thrombus in a dog

    PubMed Central

    Loewen, Jennifer M.; Cianciolo, Rachel E.; Zhang, Liwen; Yaeger, Michael; Ward, Jessica L.; Smith, Jodi D.

    2018-01-01

    Thymoma‐associated nephropathies have been reported in people but not in dogs. In this report, we describe a dog with thymoma and concurrent renal amyloidosis. A 7‐year‐old castrated male Weimaraner was presented for progressive anorexia, lethargy, and tachypnea. The dog was diagnosed with azotemia, marked proteinuria, and a thymoma that was surgically removed. Postoperatively, the dog developed a large left ventricular thrombus and was euthanized. Necropsy confirmed the presence of a left ventricular thrombus and histopathology revealed renal amyloidosis. We speculate that the renal amyloidosis occurred secondary to the thymoma, with amyloidosis in turn leading to nephrotic syndrome, hypercoagulability, and ventricular thrombosis. This case illustrates the potential for thymoma‐associated nephropathies to occur in dogs and that dogs suspected to have thymoma should have a urinalysis and urine protein creatinine ratio performed as part of the pre‐surgical database. PMID:29485186

  1. Fibrin-Targeted Magnetic Resonance Imaging Allows In Vivo Quantification of Thrombus Fibrin Content and Identifies Thrombi Amenable for Thrombolysis

    PubMed Central

    Jenkins, Julia; Modarai, Bijan; Wiethoff, Andrea J.; Phinikaridou, Alkystis; Grover, Steven P.; Patel, Ashish S.; Schaeffter, Tobias; Smith, Alberto; Botnar, Rene M.

    2014-01-01

    Objective Deep venous thrombosis is a major health problem. Thrombolytic therapies are effective in recanalizing the veins and preventing post-thrombotic complications, but there is no consensus on selection criteria. The aim of this study was to investigate a fibrin-specific MRI contrast agent (EP-2104R) for the accurate quantification of thrombus’ fibrin content in vivo and for the identification of thrombus suitable for thrombolysis. Approach and Results Venous thrombosis was induced in the inferior vena cava of 8- to 10-week-old male BALB/C mice and MRI performed 2, 4, 7, 10, 14, and 21 days later. Eighteen mice were scanned at each time point pre and 2 hours post injection of EP-2104R (8.0 μmol/kg) with 12 mice at each time point used to correlate fibrin contrast uptake with thrombus’ histological stage and fibrin content. Six mice at each time point were immediately subjected to intravascular thrombolytic therapy (10 mg/kg of tissue-type plasminogen activator). Mice were imaged to assess response to lytic therapy 24 hours after thrombolytic treatment. Two mice at each time point were scanned post injection of 0.2 mmol/kg of Gd-DTPA (gadolinium with diethylenetriaminepentacetate, Magnevist, Schering AG, Berlin, Germany) for control purpose. Contrast uptake was correlated positively with the fibrin content of the thrombus measured by Western blotting (R2=0.889; P<0.001). Thrombus relaxation rate (R1) post contrast and the change in visualized thrombus size on late gadolinium enhancement inversion recovery MRI pre–EP-2104R and post–EP-2104R injection were the best predictors for successful thrombolysis (area under the curve, 0.989 [95% confidence interval, 0.97–1.00] and 0.994 [95% confidence interval, 0.98–1.00] respectively). Conclusions MRI with a fibrin-specific contrast agent accurately estimates thrombus fibrin content in vivo and identifies thrombi that are amenable for thrombolysis. PMID:24723557

  2. Laparoscopic radical nephrectomy for a right renal tumor with renal vein tumor thrombus in a patient with situs inversus totalis.

    PubMed

    Ito, Jun; Kaiho, Yasuhiro; Iwamura, Hiromichi; Anan, Go; Sato, Makoto

    2018-05-23

    Situs inversus totalis (SIT) is a rare congenital anomaly characterized by complete inversion of the thoracic and abdominal organs. Many intra-abdominal and vessel anomalies have been reported in association with SIT. However, there have been no reports on the use of laparoscopic radical nephrectomy with thrombectomy for renal vein thrombus, which is considered as a safe and feasible procedure, in patients with SIT. We herein present the case of an 80-year-old man with SIT who was preoperatively diagnosed with a right renal tumor and renal vein tumor thrombus. The patient underwent laparoscopic right nephrectomy and tumor thrombectomy with no intraoperative complications. To ensure a safe procedure, the anatomy and vessels were carefully evaluated preoperatively using 3-D multiplanar reconstructed CT imaging. Assessing anatomical structures leads to safer laparoscopic radical nephrectomy for renal cell carcinoma with venous tumor thrombus in patients with SIT. © 2018 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and John Wiley & Sons Australia, Ltd.

  3. Blood flow and coherent vortices in the normal and aneurysmatic aortas: a fluid dynamical approach to intra-luminal thrombus formation.

    PubMed

    Biasetti, Jacopo; Hussain, Fazle; Gasser, T Christian

    2011-10-07

    Abdominal aortic aneurysms (AAAs) are frequently characterized by the development of an intra-luminal thrombus (ILT), which is known to have multiple biochemical and biomechanical implications. Development of the ILT is not well understood, and shear-stress-triggered activation of platelets could be the first step in its evolution. Vortical structures (VSs) in the flow affect platelet dynamics, which motivated the present study of a possible correlation between VS and ILT formation in AAAs. VSs educed by the λ(2)-method using computational fluid dynamics simulations of the backward-facing step problem, normal aorta, fusiform AAA and saccular AAA were investigated. Patient-specific luminal geometries were reconstructed from computed tomography scans, and Newtonian and Carreau-Yasuda models were used to capture salient rheological features of blood flow. Particularly in complex flow domains, results depended on the constitutive model. VSs developed all along the normal aorta, showing that a clear correlation between VSs and high wall shear stress (WSS) existed, and that VSs started to break up during late systole. In contrast, in the fusiform AAA, large VSs developed at sites of tortuous geometry and high WSS, occupying the entire lumen, and lasting over the entire cardiac cycle. Downward motion of VSs in the AAA was in the range of a few centimetres per cardiac cycle, and with a VS burst at that location, the release (from VSs) of shear-stress-activated platelets and their deposition to the wall was within the lower part of the diseased artery, i.e. where the thickest ILT layer is typically observed. In the saccular AAA, only one VS was found near the healthy portion of the aorta, while in the aneurysmatic bulge, no VSs occurred. We present a fluid-dynamics-motivated mechanism for platelet activation, convection and deposition in AAAs that has the potential of improving our current understanding of the pathophysiology of fluid-driven ILT growth.

  4. Dysfunctional nitric oxide signalling increases risk of myocardial infarction.

    PubMed

    Erdmann, Jeanette; Stark, Klaus; Esslinger, Ulrike B; Rumpf, Philipp Moritz; Koesling, Doris; de Wit, Cor; Kaiser, Frank J; Braunholz, Diana; Medack, Anja; Fischer, Marcus; Zimmermann, Martina E; Tennstedt, Stephanie; Graf, Elisabeth; Eck, Sebastian; Aherrahrou, Zouhair; Nahrstaedt, Janja; Willenborg, Christina; Bruse, Petra; Brænne, Ingrid; Nöthen, Markus M; Hofmann, Per; Braund, Peter S; Mergia, Evanthia; Reinhard, Wibke; Burgdorf, Christof; Schreiber, Stefan; Balmforth, Anthony J; Hall, Alistair S; Bertram, Lars; Steinhagen-Thiessen, Elisabeth; Li, Shu-Chen; März, Winfried; Reilly, Muredach; Kathiresan, Sekar; McPherson, Ruth; Walter, Ulrich; Ott, Jurg; Samani, Nilesh J; Strom, Tim M; Meitinger, Thomas; Hengstenberg, Christian; Schunkert, Heribert

    2013-12-19

    Myocardial infarction, a leading cause of death in the Western world, usually occurs when the fibrous cap overlying an atherosclerotic plaque in a coronary artery ruptures. The resulting exposure of blood to the atherosclerotic material then triggers thrombus formation, which occludes the artery. The importance of genetic predisposition to coronary artery disease and myocardial infarction is best documented by the predictive value of a positive family history. Next-generation sequencing in families with several affected individuals has revolutionized mutation identification. Here we report the segregation of two private, heterozygous mutations in two functionally related genes, GUCY1A3 (p.Leu163Phefs*24) and CCT7 (p.Ser525Leu), in an extended myocardial infarction family. GUCY1A3 encodes the α1 subunit of soluble guanylyl cyclase (α1-sGC), and CCT7 encodes CCTη, a member of the tailless complex polypeptide 1 ring complex, which, among other functions, stabilizes soluble guanylyl cyclase. After stimulation with nitric oxide, soluble guanylyl cyclase generates cGMP, which induces vasodilation and inhibits platelet activation. We demonstrate in vitro that mutations in both GUCY1A3 and CCT7 severely reduce α1-sGC as well as β1-sGC protein content, and impair soluble guanylyl cyclase activity. Moreover, platelets from digenic mutation carriers contained less soluble guanylyl cyclase protein and consequently displayed reduced nitric-oxide-induced cGMP formation. Mice deficient in α1-sGC protein displayed accelerated thrombus formation in the microcirculation after local trauma. Starting with a severely affected family, we have identified a link between impaired soluble-guanylyl-cyclase-dependent nitric oxide signalling and myocardial infarction risk, possibly through accelerated thrombus formation. Reversing this defect may provide a new therapeutic target for reducing the risk of myocardial infarction.

  5. Regulating thrombus growth and stability to achieve an optimal response to injury

    PubMed Central

    Brass, Lawrence F.; Wannemacher, Kenneth M.; Ma, Peisong; Stalker, Timothy J.

    2012-01-01

    An optimal platelet response to injury can be defined as one in which blood loss is restrained and haemostasis is achieved without the penalty of further tissue damage caused by unwarranted vascular occlusion. This brief review considers some of the ways in which thrombus growth and stability can be regulated so that an optimal platelet response can be achieved in vivo. Three related topics are considered. The first focuses on intracellular mechanisms that regulate the early events of platelet activation downstream of G protein coupled receptors for agonists such as thrombin, thromboxane A2 and ADP. The second considers the ways in which signalling events that are dependent on stable contacts between platelets can influence the state of platelet activation and thus affect thrombus growth and stability. The third focuses on the changes that are experienced by platelets as they move from their normal environment in freely-flowing plasma to a very different environment within the growing haemostatic plug, an environment in which the narrowing gaps and junctions between platelets not only facilitate communication, but also increasingly limit both the penetration of plasma and the exodus of platelet-derived bioactive molecules. PMID:21781243

  6. [Ultrasound dynamics lysis apex thrombus as an objective criterion of effectiveness of anticoagulation therapy in venous thrombosis].

    PubMed

    Kalinin, R E; Suchkov, I A; Pshennikov, A S; Agapov, A B

    2016-01-01

    To assess the effectiveness of anticoagulant therapy (ACT) for the treatment of patients with deep venous thrombosis (DVT) of the lower extremities. The study considered ultrasonic characteristics of lysis of the proximal part of thrombus: localization and nature of venous thrombosis, the length and diameter of the proximal floating part of the thrombus, and duration of the venous thrombosis. Depending on the ACT options patients were divided into 3 groups: Group 1 (18 patients) received rivaroxaban, group 2 (19 patients) received enoxaparin sodium with subsequent transition to warfarin, and 3 group (19 patietns) received enoxaparin sodium, followed by administration of rivaroxaban. Treatment with rivaroxaban was preferable over standard ACT with enoxaparin/warfarin with regards to the lysis of thrombus when duration of thrombosis did not exceed 10 days. In 10.5% of patients who received warfarin flotation of thrombi remained for 14 days; the length of the floating part of the thrombi did not exceed 3 cm. Such circumstances and inability to reach a therapeutic INR value required cava filter placement. Treatment with enoxaparin sodium followed by the administration of rivaroxaban was found to be the most efficient ACT regimen as there was no negative dynamics of ultrasound characteristics of lysis of thrombi at any duration of the disease.

  7. Diaphragm opening effects on shock wave formation and acceleration in a rectangular cross section channel

    NASA Astrophysics Data System (ADS)

    Pakdaman, S. A.; Garcia, M.; Teh, E.; Lincoln, D.; Trivedi, M.; Alves, M.; Johansen, C.

    2016-11-01

    Shock wave formation and acceleration in a high-aspect ratio cross section shock tube were studied experimentally and numerically. The relative importance of geometric effects and diaphragm opening time on shock formation are assessed. The diaphragm opening time was controlled through the use of slit-type (fast opening time) and petal-type (slow opening time) diaphragms. A novel method of fabricating the petal-type diaphragms, which results in a consistent burst pressure and symmetric opening without fragmentation, is presented. High-speed schlieren photography was used to visualize the unsteady propagation of the lead shock wave and trailing gas dynamic structures. Surface-mounted pressure sensors were used to capture the spatial and temporal development of the pressure field. Unsteady Reynolds-Averaged Navier-Stokes simulation predictions using the shear-stress-transport turbulence model are compared to the experimental data. Simulation results are used to explain the presence of high-frequency pressure oscillations observed experimentally in the driver section as well as the cause of the initial acceleration and subsequent rapid decay of shock velocity measured along the top and bottom channel surfaces. A one-dimensional theoretical model predicting the effect of the finite opening time of the diaphragm on the rate of driver depressurization and shock acceleration is proposed. The model removes the large amount of empiricism that accompanies existing models published in the literature. Model accuracy is assessed through comparisons with experiments and simulations. Limitations of and potential improvements in the model are discussed.

  8. Abrupt plate acceleration during rifted margin formation: Cause and effect

    NASA Astrophysics Data System (ADS)

    Brune, Sascha; Williams, Simon; Butterworth, Nathaniel; Müller, Dietmar

    2017-04-01

    Extension rate is known to control key processes during rifted margin formation such as crust-mantle coupling, decompression melting, magmatism, and serpentinisation. Here we build on recent advances in plate tectonic reconstructions by quantifying the extension velocity history of Earth's major rifted margins during the last 240 million years. We find that many successful rifts start with a slow phase of extension followed by rapid acceleration that introduces a fast phase. The transition from slow to fast rifting takes place long before crustal break-up: approximately half of the present day rifted margin area was created during the slow, and the other half during the fast rift phase. We reproduce the rapid transition from slow to fast extension using analytical and numerical modelling with constant force boundary conditions. In these models, rift velocities are not imposed but instead evolve naturally in response to the changing strength of the rift. Our results demonstrate that abrupt plate acceleration during continental rifting is controlled by a rift-intrinsic strength-velocity feedback. The abruptness of rift acceleration is thereby governed by the nonlinearity of lithospheric localization. Realistic brittle and power-law rheologies lead to a speed-up duration between two and ten million years. For successful rifts that generate a new ocean basin, the duration of rift speed-up is notably almost independent of the applied extensional force. Instead, the force controls the duration of the slow phase: higher forces shorten the slow phase while lower forces prolong it. If the force is too low, however, delocalisation processes prevent the rift from reaching the point of speed-up and produce a failed rift, even if the extensional system was active for many million years.

  9. A Novel Technique for Endovascular Removal of Large Volume Right Atrial Tumor Thrombus

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nickel, Barbara, E-mail: nickel.ba@gmail.com; McClure, Timothy, E-mail: tmcclure@gmail.com; Moriarty, John, E-mail: jmoriarty@mednet.ucla.edu

    Venous thromboembolic disease is a significant cause of morbidity and mortality, particularly in the setting of large volume pulmonary embolism. Thrombolytic therapy has been shown to be a successful treatment modality; however, its use somewhat limited due to the risk of hemorrhage and potential for distal embolization in the setting of large mobile thrombi. In patients where either thrombolysis is contraindicated or unsuccessful, and conventional therapies prove inadequate, surgical thrombectomy may be considered. We present a case of percutaneous endovascular extraction of a large mobile mass extending from the inferior vena cava into the right atrium using the Angiovac device,more » a venovenous bypass system designed for high-volume aspiration of undesired endovascular material. Standard endovascular methods for removal of cancer-associated thrombus, such as catheter-directed lysis, maceration, and exclusion, may prove inadequate in the setting of underlying tumor thrombus. Where conventional endovascular methods either fail or are unsuitable, endovascular thrombectomy with the Angiovac device may be a useful and safe minimally invasive alternative to open resection.« less

  10. The perioperative management of an inferior vena caval tumor thrombus in patients with renal cell carcinoma.

    PubMed

    Woodruff, Daniel Y; Van Veldhuizen, Peter; Muehlebach, Gregory; Johnson, Phillip; Williamson, Timothy; Holzbeierlein, Jeffrey M

    2013-07-01

    Inferior vena caval tumor thrombus (IVC-TT) occurs in 10% of patients diagnosed with renal cell carcinoma (RCC). The perioperative management of these patients remains challenging. Despite multiple publications outlining surgical approaches and outcomes there have been few studies detailing the best peri-operative management of patients with IVC-TT. Our goal was to define the optimal management of patients with RCC and IVC-TT. A review of all published literature regarding the management of RCC with IVC-TT was performed utilizing Pub Med and the Cochrane Database. Reviews were also made of all relevant literature regarding the need for cardiopulmonary bypass and recommendations regarding thrombus in any location in patients with malignancy. Specific items critically examined included: need for preoperative heart catheterization, need for anticoagulation and type of anticoagulation, need for additional studies such as lower extremity duplex or venogram, and indications for vena caval filter placement. The results were then presented to a multidisciplinary group made up of experts in the fields of Urology, Hematology, Oncology, Cardiothoracic Surgery, Interventional Radiology, and Pulmonary/Critical Care. Based on the available literature a best practice guidelines regarding the management of RCC with IVC-TT was established at our institution. Our institutional recommendations include (1) preoperative cardiac catheterization in all patients believed to require cardiopulmonary bypass for removal of the thrombus but only cardiac clearance for those who bypass is unlikely, (2) preoperative anticoagulation using a low molecular weight heparin such as enoxaparin unless contraindicated due to bleeding from the tumor or other contraindication, (3) avoidance of vena caval filters whenever possible is recommended due the potential for caval thrombosis and the difficulties they present during surgical resection. This study identified the available literature on the management

  11. Interobserver variability in target definition for hepatocellular carcinoma with and without portal vein thrombus: radiation therapy oncology group consensus guidelines.

    PubMed

    Hong, Theodore S; Bosch, Walter R; Krishnan, Sunil; Kim, Tae K; Mamon, Harvey J; Shyn, Paul; Ben-Josef, Edgar; Seong, Jinsil; Haddock, Michael G; Cheng, Jason C; Feng, Mary U; Stephans, Kevin L; Roberge, David; Crane, Christopher; Dawson, Laura A

    2014-07-15

    Defining hepatocellular carcinoma (HCC) gross tumor volume (GTV) requires multimodal imaging, acquired in different perfusion phases. The purposes of this study were to evaluate the variability in contouring and to establish guidelines and educational recommendations for reproducible HCC contouring for treatment planning. Anonymous, multiphasic planning computed tomography scans obtained from 3 patients with HCC were identified and distributed to a panel of 11 gastrointestinal radiation oncologists. Panelists were asked the number of HCC cases they treated in the past year. Case 1 had no vascular involvement, case 2 had extensive portal vein involvement, and case 3 had minor branched portal vein involvement. The agreement between the contoured total GTVs (primary + vascular GTV) was assessed using the generalized kappa statistic. Agreement interpretation was evaluated using Landis and Koch's interpretation of strength of agreement. The S95 contour, defined using the simultaneous truth and performance level estimation (STAPLE) algorithm consensus at the 95% confidence level, was created for each case. Of the 11 panelists, 3 had treated >25 cases in the past year, 2 had treated 10 to 25 cases, 2 had treated 5 to 10 cases, 2 had treated 1 to 5 cases, 1 had treated 0 cases, and 1 did not respond. Near perfect agreement was seen for case 1, and substantial agreement was seen for cases 2 and 3. For case 2, there was significant heterogeneity in the volume identified as tumor thrombus (range 0.58-40.45 cc). For case 3, 2 panelists did not include the branched portal vein thrombus, and 7 panelists contoured thrombus separately from the primary tumor, also showing significant heterogeneity in volume of tumor thrombus (range 4.52-34.27 cc). In a group of experts, excellent agreement was seen in contouring total GTV. Heterogeneity exists in the definition of portal vein thrombus that may impact treatment planning, especially if differential dosing is contemplated. Guidelines

  12. Interobserver Variability in Target Definition for Hepatocellular Carcinoma With and Without Portal Vein Thrombus: Radiation Therapy Oncology Group Consensus Guidelines

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hong, Theodore S., E-mail: tshong1@mgh.harvard.edu; Bosch, Walter R.; Krishnan, Sunil

    2014-07-15

    Purpose: Defining hepatocellular carcinoma (HCC) gross tumor volume (GTV) requires multimodal imaging, acquired in different perfusion phases. The purposes of this study were to evaluate the variability in contouring and to establish guidelines and educational recommendations for reproducible HCC contouring for treatment planning. Methods and Materials: Anonymous, multiphasic planning computed tomography scans obtained from 3 patients with HCC were identified and distributed to a panel of 11 gastrointestinal radiation oncologists. Panelists were asked the number of HCC cases they treated in the past year. Case 1 had no vascular involvement, case 2 had extensive portal vein involvement, and case 3more » had minor branched portal vein involvement. The agreement between the contoured total GTVs (primary + vascular GTV) was assessed using the generalized kappa statistic. Agreement interpretation was evaluated using Landis and Koch's interpretation of strength of agreement. The S95 contour, defined using the simultaneous truth and performance level estimation (STAPLE) algorithm consensus at the 95% confidence level, was created for each case. Results: Of the 11 panelists, 3 had treated >25 cases in the past year, 2 had treated 10 to 25 cases, 2 had treated 5 to 10 cases, 2 had treated 1 to 5 cases, 1 had treated 0 cases, and 1 did not respond. Near perfect agreement was seen for case 1, and substantial agreement was seen for cases 2 and 3. For case 2, there was significant heterogeneity in the volume identified as tumor thrombus (range 0.58-40.45 cc). For case 3, 2 panelists did not include the branched portal vein thrombus, and 7 panelists contoured thrombus separately from the primary tumor, also showing significant heterogeneity in volume of tumor thrombus (range 4.52-34.27 cc). Conclusions: In a group of experts, excellent agreement was seen in contouring total GTV. Heterogeneity exists in the definition of portal vein thrombus that may impact treatment

  13. Thrombospondin-1 controls vascular platelet recruitment and thrombus adherence in mice by protecting (sub)endothelial VWF from cleavage by ADAMTS13

    PubMed Central

    Bonnefoy, Arnaud; Daenens, Kim; Feys, Hendrik B.; De Vos, Rita; Vandervoort, Petra; Vermylen, Jos; Lawler, Jack; Hoylaerts, Marc F.

    2006-01-01

    The function of thrombospondin-1 (TSP-1) in hemostasis was investigated in wild-type (WT) and Tsp1-/- mice, via dynamic platelet interaction studies with A23187-stimulated mesenteric endothelium and with photochemically injured cecum subendothelium. Injected calcein-labeled WT platelets tethered or firmly adhered to almost all A23187-stimulated blood vessels of WT mice, but Tsp1-/- platelets tethered to 45% and adhered to 25.8% of stimulated Tsp1-/- vessels only. Stimulation generated temporary endothelium-associated ultralarge von Willebrand factor (VWF) multimers, triggering platelet string formation in 48% of WT versus 20% of Tsp1-/- vessels. Injection of human TSP-1 or thrombotic thrombocytopenic purpura (TTP) patient-derived neutralizing anti-ADAMTS13 antibodies corrected the defective platelet recruitment in Tsp1-/- mice, while having a moderate effect in WT mice. Photochemical injury of intestinal blood vessels induced thrombotic occlusions with longer occlusion times in Tsp1-/- venules (1027 ± 377 seconds) and arterioles (858 ± 289 seconds) than in WT vessels (559 ± 241 seconds, P < .001; 443 ± 413 seconds, P < .003) due to defective thrombus adherence, resulting in embolization of complete thrombi, a defect restored by both human TSP-1 and anti-ADAMTS13 antibodies. We conclude that in a shear field, soluble or local platelet-released TSP-1 can protect unfolded endothelium-bound and subendothelial VWF from degradation by plasma ADAMTS13, thus securing platelet tethering and thrombus adherence to inflamed and injured endothelium, respectively. PMID:16204318

  14. Numerical simulation of particle jet formation induced by shock wave acceleration in a Hele-Shaw cell

    NASA Astrophysics Data System (ADS)

    Osnes, A. N.; Vartdal, M.; Pettersson Reif, B. A.

    2018-05-01

    The formation of jets from a shock-accelerated cylindrical shell of particles, confined in a Hele-Shaw cell, is studied by means of numerical simulation. A number of simulations have been performed, systematically varying the coupling between the gas and solid phases in an effort to identify the primary mechanism(s) responsible for jet formation. We find that coupling through drag is sufficient for the formation of jets. Including the effect of particle volume fraction and particle collisions did not alter the general behaviour, but had some influence on the length, spacing and number of jets. Furthermore, we find that the jet selection process starts early in the dispersal process, during the initial expansion of the particle layer.

  15. A low-dose, dual-phase cardiovascular CT protocol to assess left atrial appendage anatomy and exclude thrombus prior to left atrial intervention.

    PubMed

    Lazoura, Olga; Ismail, Tevfik F; Pavitt, Christopher; Lindsay, Alistair; Sriharan, Mona; Rubens, Michael; Padley, Simon; Duncan, Alison; Wong, Tom; Nicol, Edward

    2016-02-01

    Assessment of the left atrial appendage (LAA) for thrombus and anatomy is important prior to atrial fibrillation (AF) ablation and LAA exclusion. The use of cardiovascular CT (CCT) to detect LAA thrombus has been limited by the high incidence of pseudothrombus on single-pass studies. We evaluated the diagnostic accuracy of a two-phase protocol incorporating a limited low-dose delayed contrast-enhanced examination of the LAA, compared with a single-pass study for LAA morphological assessment, and transesophageal echocardiography (TEE) for the exclusion of thrombus. Consecutive patients (n = 122) undergoing left atrial interventions for AF were assessed. All had a two-phase CCT protocol (first-past scan plus a limited, 60-s delayed scan of the LAA) and TEE. Sensitivity, specificity, diagnostic accuracy, positive (PPV) and negative predictive values (NPV) were calculated for the detection of true thrombus on first-pass and delayed scans, using TEE as the gold standard. Overall, 20/122 (16.4 %) patients had filling defects on the first-pass study. All affected the full delineation of the LAA morphology; 17/20 (85 %) were confirmed as pseudo-filling defects. Three (15 %) were seen on late-pass and confirmed as true thrombi on TEE; a significant improvement in diagnostic performance relative to a single-pass scan (McNemar Chi-square 17, p < 0.001). The sensitivity, specificity, diagnostic accuracy, PPV and NPV was 100, 85.7, 86.1, 15.0 and 100 % respectively for first-pass scans, and 100 % for all parameters for the delayed scans. The median (range) additional radiation dose for the delayed scan was 0.4 (0.2-0.6) mSv. A low-dose delayed scan significantly improves the identification of true LAA anatomy and thrombus in patients undergoing LA intervention.

  16. Blood Accessibility to Fibrin in Venous Thrombosis is Thrombus Age-Dependent and Predicts Fibrinolytic Efficacy: An In Vivo Fibrin Molecular Imaging Study

    PubMed Central

    Stein-Merlob, Ashley F.; Kessinger, Chase W.; Erdem, S. Sibel; Zelada, Henry; Hilderbrand, Scott A.; Lin, Charles P.; Tearney, Guillermo J.; Jaff, Michael R.; Reed, Guy L.; Henke, Peter K.; McCarthy, Jason R.; Jaffer, Farouc A.

    2015-01-01

    Fibrinolytic therapy of venous thromboembolism (VTE) is increasingly utilized, yet limited knowledge is available regarding in vivo mechanisms that govern fibrinolytic efficacy. In particular, it is unknown how age-dependent thrombus organization limits direct blood contact with fibrin, the target of blood-based fibrinolytic agents. Utilizing high-resolution in vivo optical molecular imaging with FTP11, a near-infrared fluorescence (NIRF) fibrin-specific reporter, here we investigated the in vivo interrelationships of blood accessibility to fibrin, thrombus age, thrombus neoendothelialization, and fibrinolysis in murine venous thrombosis (VT). In both stasis VT and non-stasis VT, NIRF microscopy showed that FTP11 fibrin binding was thrombus age-dependent. FTP11 localized to the luminal surface of early-stage VT, but only minimally to subacute VT (p<0.001). Transmission electron microscopy of early stage VT revealed direct blood cell contact with luminal fibrin-rich surfaces. In contrast, subacute VT exhibited an encasing CD31+ neoendothelial layer that limited blood cell contact with thrombus fibrin in both VT models. Next we developed a theranostic strategy to predict fibrinolytic efficacy based on the in vivo fibrin accessibility to blood NIRF signal. Mice with variably aged VT underwent FTP11 injection and intravital microscopy (IVM), followed by tissue plasminogen activator infusion to induce VT fibrinolysis. Fibrin molecular IVM revealed that early stage VT, but not subacute VT, bound FTP11 (p<0.05), and experienced higher rates of fibrinolysis and total fibrinolysis (p<0.05 vs. subacute VT). Before fibrinolysis, the baseline FTP11 NIRF signal predicted the net fibrinolysis at 60 minutes (p<0.001). Taken together, these data provide novel insights into the temporal evolution of VT and its susceptibility to therapeutic fibrinolysis. Fibrin molecular imaging may provide a theranostic strategy to identify venous thrombi amenable to fibrinolytic therapies. PMID

  17. Thrombus in Transit: A Potentially Life-threatening Complication of Cerebral Sinus Thrombosis.

    PubMed

    Petracca, Martina; Calandrelli, Rosalinda; Broccolini, Aldobrando; Caliandro, Pietro; Della Marca, Giacomo; Frisullo, Giovanni; Morosetti, Roberta; Profice, Paolo; Lamendola, Priscilla; Pennestrì, Faustino; Pilato, Fabio

    2017-01-01

    We report the case of a 41-year-old, 7-weeks-pregnant patient, presenting with headache and generalized seizure due to cerebral venous thrombosis complicated by jugular thrombosis and thrombus dislocation into right cardiac cavities. The patient was treated with intravenous heparin, and underwent embolectomy in extracorporeal circulation. This case illustrates the variability of cerebral venous thrombosis progression and a potentially life-threatening condition even during anticoagulant therapy.

  18. Carbon nanotubes with high bone-tissue compatibility and bone-formation acceleration effects.

    PubMed

    Usui, Yuki; Aoki, Kaoru; Narita, Nobuyo; Murakami, Narumichi; Nakamura, Isao; Nakamura, Koichi; Ishigaki, Norio; Yamazaki, Hiroshi; Horiuchi, Hiroshi; Kato, Hiroyuki; Taruta, Seiichi; Kim, Yoong Ahm; Endo, Morinobu; Saito, Naoto

    2008-02-01

    Carbon nanotubes (CNTs) have been used in various fields as composites with other substances or alone to develop highly functional materials. CNTs hold great interest with respect to biomaterials, particularly those to be positioned in contact with bone such as prostheses for arthroplasty, plates or screws for fracture fixation, drug delivery systems, and scaffolding for bone regeneration. Accordingly, bone-tissue compatibility of CNTs and CNT influence on bone formation are important issues, but the effects of CNTs on bone have not been delineated. Here, it is found that multi-walled CNTs adjoining bone induce little local inflammatory reaction, show high bone-tissue compatibility, permit bone repair, become integrated into new bone, and accelerate bone formation stimulated by recombinant human bone morphogenetic protein-2 (rhBMP-2). This study provides an initial investigational basis for CNTs in biomaterials that are used adjacent to bone, including uses to promote bone regeneration. These findings should encourage development of clinical treatment modalities involving CNTs.

  19. Culprit lesion thrombus burden after manual thrombectomy or percutaneous coronary intervention-alone in ST-segment elevation myocardial infarction: the optical coherence tomography sub-study of the TOTAL (ThrOmbecTomy versus PCI ALone) trial.

    PubMed

    Bhindi, Ravinay; Kajander, Olli A; Jolly, Sanjit S; Kassam, Saleem; Lavi, Shahar; Niemelä, Kari; Fung, Anthony; Cheema, Asim N; Meeks, Brandi; Alexopoulos, Dimitrios; Kočka, Viktor; Cantor, Warren J; Kaivosoja, Timo P; Shestakovska, Olga; Gao, Peggy; Stankovic, Goran; Džavík, Vladimír; Sheth, Tej

    2015-08-01

    Manual thrombectomy has been proposed as a strategy to reduce thrombus burden during primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). However, the effectiveness of manual thrombectomy in reducing thrombus burden is uncertain. In this substudy of the TOTAL (ThrOmbecTomy versus PCI ALone) trial, we compared the thrombus burden at the culprit lesion using optical coherence tomography (OCT) in patients treated with thrombectomy vs. PCI-alone. The TOTAL trial (N = 10 732) was an international, multicentre, randomized trial of thrombectomy (using the Export catheter, Medtronic Cardiovascular, Santa Rosa, CA, USA) in STEMI patients treated with primary PCI. The OCT substudy prospectively enrolled 214 patients from 13 sites in 5 countries. Optical coherence tomography was performed immediately after thrombectomy or PCI-alone and then repeated after stent deployment. Thrombus quantification was performed by an independent core laboratory blinded to treatment assignment. The primary outcome of pre-stent thrombus burden as a percentage of segment analysed was 2.36% (95% CI: 1.73-3.22) in the thrombectomy group and 2.88% (95% CI: 2.12-3.90) in the PCI-alone group (P = 0.373). Absolute pre-stent thrombus volume was not different (2.99 vs. 3.74 mm(3), P = 0.329). Other secondary outcomes of pre-stent quadrants of thrombus, post-stent atherothrombotic burden, and post-stent atherothrombotic volume were not different between groups. Manual thrombectomy did not reduce pre-stent thrombus burden at the culprit lesion compared with PCI-alone. Both strategies were associated with low thrombus burden at the lesion site after the initial intervention to restore flow. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  20. The effect of a dual or a triple antithrombotic therapy with apixaban on thrombus formation in vivo and in an ex vivo perfusion chamber model

    PubMed Central

    Weisshaar, Stefan; Litschauer, Brigitte; Bucher, Sebastian; Riesenhuber, Martin; Kapiotis, Stylianos; Kyrle, Paul Alexander; Wolzt, Michael

    2016-01-01

    Abstract Background: There is a need to optimize pharmacological treatment in patients with acute coronary syndrome and concomitant atrial fibrillation, in particular with newer antithrombotic medicines. We have therefore studied if dual or triple combination of antithrombotic agents exert similar effects on coagulation activation in an in vivo model in the skin microvasculature and in an ex vivo perfusion chamber. Methods and Results: Shed blood platelet activation (β-thromboglobulin [β-TG]), thrombin generation (thrombin-antithrombin complex [TAT]) and volume as well as markers of thrombus size (D-dimer) and its platelet content (P-selectin) in a perfusion chamber were studied in a sequential, open-label, parallel group trial in 40 healthy male volunteers (n = 20 per group). Subjects received ticagrelor and apixaban without or with acetylsalicylic acid (ASA). Outcome parameters were assessed at 3 hours after therapy dosing, and at steady-state trough and peak conditions. A triple or dual therapy induced a comparable decrease in shed blood β-TG at 3 hours after therapy dosing but was more pronounced at steady-state conditions with the more intense treatment combination. During both antithrombotic regimens a similarly sustained inhibition in thrombin generation was observed which was accompanied by comparable increases in shed blood volume. In contrast, no treatment effect could be observed in the perfusion chamber experiment. Conclusion: Ticagrelor and apixaban with or without ASA inhibit platelet activation and thrombin formation in vivo in healthy subjects. Platelet inhibition was greater at steady-state conditions after triple therapy administration. PMID:27399131

  1. Accelerated gravity testing of aquitard core permeability and implications at formation and regional scale

    NASA Astrophysics Data System (ADS)

    Timms, W. A.; Crane, R.; Anderson, D. J.; Bouzalakos, S.; Whelan, M.; McGeeney, D.; Rahman, P. F.; Acworth, R. I.

    2016-01-01

    Evaluating the possibility of leakage through low-permeability geological strata is critically important for sustainable water supplies, the extraction of fuels from coal and other strata, and the confinement of waste within the earth. The current work demonstrates that relatively rapid and realistic vertical hydraulic conductivity (Kv) measurements of aquitard cores using accelerated gravity can constrain and compliment larger-scale assessments of hydraulic connectivity. Steady-state fluid velocity through a low-K porous sample is linearly related to accelerated gravity (g level) in a centrifuge permeameter (CP) unless consolidation or geochemical reactions occur. A CP module was custom designed to fit a standard 2 m diameter geotechnical centrifuge (550 g maximum) with a capacity for sample dimensions up to 100 mm diameter and 200 mm length, and a total stress of ˜ 2 MPa at the base of the core. Formation fluids were used as influent to limit any shrink-swell phenomena, which may alter the permeability. Kv results from CP testing of minimally disturbed cores from three sites within a clayey-silt formation varied from 10-10 to 10-7 m s-1 (number of samples, n = 18). Additional tests were focussed on the Cattle Lane (CL) site, where Kv within the 99 % confidence interval (n = 9) was 1.1 × 10-9 to 2.0 × 10-9 m s-1. These Kv results were very similar to an independent in situ Kv method based on pore pressure propagation though the sequence. However, there was less certainty at two other core sites due to limited and variable Kv data. Blind standard 1 g column tests underestimated Kv compared to CP and in situ Kv data, possibly due to deionised water interactions with clay, and were more time-consuming than CP tests. Our Kv results were compared with the set-up of a flow model for the region, and considered in the context of heterogeneity and preferential flow paths at site and

  2. Acceleration of atherogenesis by COX-1-dependent prostanoid formation in low density lipoprotein receptor knockout mice.

    PubMed

    Praticò, D; Tillmann, C; Zhang, Z B; Li, H; FitzGerald, G A

    2001-03-13

    The cyclooxygenase (COX) product, prostacyclin (PGI(2)), inhibits platelet activation and vascular smooth-muscle cell migration and proliferation. Biochemically selective inhibition of COX-2 reduces PGI(2) biosynthesis substantially in humans. Because deletion of the PGI(2) receptor accelerates atherogenesis in the fat-fed low density lipoprotein receptor knockout mouse, we wished to determine whether selective inhibition of COX-2 would accelerate atherogenesis in this model. To address this hypothesis, we used dosing with nimesulide, which inhibited COX-2 ex vivo, depressed urinary 2,3 dinor 6-keto PGF(1alpha) by approximately 60% but had no effect on thromboxane formation by platelets, which only express COX-1. By contrast, the isoform nonspecific inhibitor, indomethacin, suppressed platelet function and thromboxane formation ex vivo and in vivo, coincident with effects on PGI(2) biosynthesis indistinguishable from nimesulide. Indomethacin reduced the extent of atherosclerosis by 55 +/- 4%, whereas nimesulide failed to increase the rate of atherogenesis. Despite their divergent effects on atherogenesis, both drugs depressed two indices of systemic inflammation, soluble intracellular adhesion molecule-1, and monocyte chemoattractant protein-1 to a similar but incomplete degree. Neither drug altered serum lipids and the marked increase in vascular expression of COX-2 during atherogenesis. Accelerated progression of atherosclerosis is unlikely during chronic intake of specific COX-2 inhibitors. Furthermore, evidence that COX-1-derived prostanoids contribute to atherogenesis suggests that controlled evaluation of the effects of nonsteroidal anti-inflammatory drugs and/or aspirin on plaque progression in humans is timely.

  3. One-Dimensional Shock Wave Formation by an Accelerating Piston. Ph.D. Thesis - Ohio State Univ.

    NASA Technical Reports Server (NTRS)

    Mann, M. J.

    1970-01-01

    The formation of a shock wave by a solid accelerating piston was studied. A theoretical solution using the method of characteristics for a perfect gas showed that a complex wave system exists, and that the compressed gas can have large gradients in temperature, density and entropy. Experiments were performed with a piston tube where piston speed, shock speed and pressure were measured. The comparison of theory and experiment was good.

  4. Particle radiotherapy, a novel external radiation therapy, versus liver resection for hepatocellular carcinoma accompanied with inferior vena cava tumor thrombus: A matched-pair analysis.

    PubMed

    Komatsu, Shohei; Kido, Masahiro; Asari, Sadaki; Toyama, Hirochika; Ajiki, Tetsuo; Demizu, Yusuke; Terashima, Kazuki; Okimoto, Tomoaki; Sasaki, Ryohei; Fukumoto, Takumi

    2017-12-01

    Hepatocellular carcinoma accompanied with inferior vena cava tumor thrombus carries a dismal prognosis, and the feasibility of local treatment has remained controversial. The present study aimed to compare the outcomes of particle radiotherapy and liver resection in patients with hepatocellular carcinoma with inferior vena cava tumor thrombus. Thirty-one and 19 patients, respectively, underwent particle radiotherapy and liver resection for hepatocellular carcinoma with inferior vena cava tumor thrombus. A matched-pair analysis was undertaken to compare the short- and long-term outcomes according to tumor stage determined using the tumor-node-metastasis classification. Both stages IIIB and IV (IVA and IVB) patients were well-matched for 12 factors, including treatment policy and patient and tumor characteristics. The median survival time of matched patients with stage IIIB tumors in the particle radiotherapy group was greater than that in the liver resection group (748 vs 272 days, P = .029), whereas no significant difference was observed in the median survival times of patients with stage IV tumors (239 vs 311 days, respectively). There were significantly fewer treatment-related complications of grade 3 or greater in the particle radiotherapy group (0%) than in the liver resection group (26%). Particle radiotherapy is potentially preferable in hepatocellular carcinoma patients with stage IIIB inferior vena cava tumor thrombus and at least equal in efficiency to liver resection in those with stage IV disease, while causing significantly fewer complications. Considering the relatively high survival and low invasiveness of particle radiotherapy when compared to liver resection, this approach may represent a novel treatment modality for hepatocellular carcinoma with inferior vena cava tumor thrombus. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Load-sharing through elastic micro-motion accelerates bone formation and interbody fusion.

    PubMed

    Ledet, Eric H; Sanders, Glenn P; DiRisio, Darryl J; Glennon, Joseph C

    2018-02-13

    Achieving a successful spinal fusion requires the proper biological and biomechanical environment. Optimizing load-sharing in the interbody space can enhance bone formation. For anterior cervical discectomy and fusion (ACDF), loading and motion are largely dictated by the stiffness of the plate, which can facilitate a balance between stability and load-sharing. The advantages of load-sharing may be substantial for patients with comorbidities and in multilevel procedures where pseudarthrosis rates are significant. We aimed to evaluate the efficacy of a novel elastically deformable, continuously load-sharing anterior cervical spinal plate for promotion of bone formation and interbody fusion relative to a translationally dynamic plate. An in vivo animal model was used to evaluate the effects of an elastically deformable spinal plate on bone formation and spine fusion. Fourteen goats underwent an ACDF and received either a translationally dynamic or elastically deformable plate. Animals were followed up until 18 weeks and were evaluated by plain x-ray, computed tomography scan, and undecalcified histology to evaluate the rate and quality of bone formation and interbody fusion. Animals treated with the elastically deformable plate demonstrated statistically significantly superior early bone formation relative to the translationally dynamic plate. Trends in the data from 8 to 18 weeks postoperatively suggest that the elastically deformable implant enhanced bony bridging and fusion, but these enhancements were not statistically significant. Load-sharing through elastic micro-motion accelerates bone formation in the challenging goat ACDF model. The elastically deformable implant used in this study may promote early bony bridging and increased rates of fusion, but future studies will be necessary to comprehensively characterize the advantages of load-sharing through micro-motion. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Magnetic resonance direct thrombus imaging of the evolution of acute deep vein thrombosis of the leg.

    PubMed

    Westerbeek, R E; Van Rooden, C J; Tan, M; Van Gils, A P G; Kok, S; De Bats, M J; De Roos, A; Huisman, M V

    2008-07-01

    Accurate diagnosis of acute recurrent deep vein thrombosis (DVT) is relevant to avoid improper diagnosis and unnecessary life-long anticoagulant treatment. Compression ultrasound has high accuracy for a first episode of DVT, but is often unreliable in suspected recurrent disease. Magnetic resonance direct thrombus imaging (MR DTI) has been shown to accurately detect acute DVT. The purpose of this prospective study was to determine the MR signal change during 6 months follow-up in patients with acute DVT. This study was a prospective study of 43 consecutive patients with a first episode of acute DVT demonstrated by compression ultrasound. All patients underwent MR DTI. Follow-up was performed with MR-DTI and compression ultrasound at 3 and 6 months respectively. All data were coded, stored and assessed by two blinded observers. MR direct thrombus imaging identified acute DVT in 41 of 43 patients (sensitivity 95%). There was no abnormal MR-signal in controls, or in the contralateral extremity of patients with DVT (specificity 100%). In none of the 39 patients available at 6 months follow-up was the abnormal MR-signal at the initial acute DVT observed, whereas in 12 of these patients (30.8%) compression ultrasound was still abnormal. Magnetic resonance direct thrombus imaging normalizes over a period of 6 months in all patients with diagnosed DVT, while compression ultrasound remains abnormal in a third of these patients. MR-DTI may potentially allow for accurate detection in patients with acute suspected recurrent DVT, and this should be studied prospectively.

  7. Long-term survival after liver transplant for recurrent hepatocellular carcinoma with bile duct tumor thrombus: case report.

    PubMed

    Liu, Chao; Wang, Jie

    2012-12-01

    Hepatocellular carcinoma with bile duct tumor thrombus is considered an aggressive malignancy, and the prognosis of liver transplant for it remains obscure. A 42-year-old man with recurrent hepatocellular carcinoma and a history of surgical resection was admitted to our hospital with a 10-day history of yellowish urine and itchy skin. There were 3 lesions in the right lobe with the diameter of 2 cm each. A mass was found in the upper part of common bile duct, and the intrahepatic bile duct was dilated. His serum alpha-fetoprotein level was 2476 μg/L, total bilirubin level was 327 μmol/L, direct bilirubin level was 261 μmol/L, and alanine aminotransferase was 714 U/L. There was no main portal vein thrombus or extrahepatic metastases. Because of his poor liver function, he was listed for a liver transplant. During the wait (30 d), he underwent 9 episodes of plasmapheresis to decrease the serum level of bilirubin. He had an orthotopic liver transplant with the graft from a deceased donor. After the liver transplant, he received 5 cycles of chemotherapy with the regimen of oxaliplatin and 5-fluorouracil. This patient has survived without recurrence of hepatocellular carcinoma for more than 82 months and remains in good condition. Liver transplant may have a favorable result for hepatocellular carcinoma patient with a bile duct tumor thrombus, within the Milan criteria.

  8. Overwork accelerates thrombotic reaction: implications for the pathogenesis of Karoshi.

    PubMed

    Otsui, Kazunori; Yamamoto, Junichiro; Inoue, Nobutaka

    2018-02-01

    Work-related stressors are potential causes of cardiovascular diseases (CVDs) and stroke; however, the pathophysiological mechanisms by which occupational stress induces and exacerbates CVDs remain unclear. The global thrombosis test (GTT) is a novel in vitro assay for evaluating both thrombotic reactions and subsequent thrombolysis. The time required to form an occlusive thrombus with the GTT, called as the occlusion time (OT), and the time to lyse the thrombus, the lysis time (LT), are markers of thrombotic and thrombolytic reactions, respectively. We investigated the impact of work-related stress on the thrombotic and thrombolytic reactions in 46 healthy medical residents. Off-duty or on-duty blood samples were collected on the mornings of non-work days or after the night duty on the emergent room respectively. The duration of sleep was significantly shorter during night duty than during off-duty nights [2.25 (1.0, 3.0) h vs. 6.0 (5.0, 7.0) h; p < 0.001]. Baseline OT was 310.3 (260.9, 437.7) s. whereas the on-duty OT was significantly shortened [284.2 (230.5, 355.8) s; p < 0.01]. LT was significantly prolonged during overwork conditions compared with off-duty conditions [1547 (1346, 1908) s vs. 1470 (1219, 1692) s; p < 0.05]. Overwork accelerates the thrombotic reactions. These reactions might explain the pathogenesis of overwork-related CVDs. The GTT is a good tool for evaluating of the level of fatigue.

  9. Accelerated Electron-Beam Formation with a High Capture Coefficient in a Parallel Coupled Accelerating Structure

    NASA Astrophysics Data System (ADS)

    Chernousov, Yu. D.; Shebolaev, I. V.; Ikryanov, I. M.

    2018-01-01

    An electron beam with a high (close to 100%) coefficient of electron capture into the regime of acceleration has been obtained in a linear electron accelerator based on a parallel coupled slow-wave structure, electron gun with microwave-controlled injection current, and permanent-magnet beam-focusing system. The high capture coefficient was due to the properties of the accelerating structure, beam-focusing system, and electron-injection system. Main characteristics of the proposed systems are presented.

  10. Temporary dietary iron restriction affects the process of thrombus resolution in a rat model of deep vein thrombosis.

    PubMed

    Oboshi, Makiko; Naito, Yoshiro; Sawada, Hisashi; Hirotani, Shinichi; Iwasaku, Toshihiro; Okuhara, Yoshitaka; Morisawa, Daisuke; Eguchi, Akiyo; Nishimura, Koichi; Fujii, Kenichi; Mano, Toshiaki; Ishihara, Masaharu; Masuyama, Tohru

    2015-01-01

    Deep vein thrombosis (DVT) is a major cause of pulmonary thromboembolism and sudden death. Thus, it is important to consider the pathophysiology of DVT. Recently, iron has been reported to be associated with thrombotic diseases. Hence, in this study, we investigate the effects of dietary iron restriction on the process of thrombus resolution in a rat model of DVT. We induced DVT in 8-week-old male Sprague-Dawley rats by performing ligations of their inferior venae cavae. The rats were then given either a normal diet (DVT group) or an iron-restricted diet (DVT+IR group). Thrombosed inferior venae cavae were harvested at 5 days after ligation. The iron-restricted diet reduced venous thrombus size compared to the normal diet. Intrathrombotic collagen content was diminished in the DVT+IR group compared to the DVT group. In addition, intrathrombotic gene expression and the activity of matrix metalloproteinase-9 were increased in the DVT+IR group compared to the DVT group. Furthermore, the DVT+IR group had greater intrathrombotic neovascularization as well as higher gene expression levels of urokinase-type plasminogen activator and tissue-type plasminogen activator than the DVT group. The iron-restricted diet decreased intrathrombotic superoxide production compared to the normal diet. These results suggest that dietary iron restriction affects the process of thrombus resolution in DVT.

  11. Temporary Dietary Iron Restriction Affects the Process of Thrombus Resolution in a Rat Model of Deep Vein Thrombosis

    PubMed Central

    Oboshi, Makiko; Naito, Yoshiro; Sawada, Hisashi; Hirotani, Shinichi; Iwasaku, Toshihiro; Okuhara, Yoshitaka; Morisawa, Daisuke; Eguchi, Akiyo; Nishimura, Koichi; Fujii, Kenichi; Mano, Toshiaki; Ishihara, Masaharu; Masuyama, Tohru

    2015-01-01

    Background Deep vein thrombosis (DVT) is a major cause of pulmonary thromboembolism and sudden death. Thus, it is important to consider the pathophysiology of DVT. Recently, iron has been reported to be associated with thrombotic diseases. Hence, in this study, we investigate the effects of dietary iron restriction on the process of thrombus resolution in a rat model of DVT. Methods We induced DVT in 8-week-old male Sprague-Dawley rats by performing ligations of their inferior venae cavae. The rats were then given either a normal diet (DVT group) or an iron-restricted diet (DVT+IR group). Thrombosed inferior venae cavae were harvested at 5 days after ligation. Results The iron-restricted diet reduced venous thrombus size compared to the normal diet. Intrathrombotic collagen content was diminished in the DVT+IR group compared to the DVT group. In addition, intrathrombotic gene expression and the activity of matrix metalloproteinase-9 were increased in the DVT+IR group compared to the DVT group. Furthermore, the DVT+IR group had greater intrathrombotic neovascularization as well as higher gene expression levels of urokinase-type plasminogen activator and tissue-type plasminogen activator than the DVT group. The iron-restricted diet decreased intrathrombotic superoxide production compared to the normal diet. Conclusions These results suggest that dietary iron restriction affects the process of thrombus resolution in DVT. PMID:25962140

  12. Non-vitamin K antagonist oral anticoagulants versus warfarin for the prevention of spontaneous echo-contrast and thrombus in patients with atrial fibrillation or flutter undergoing cardioversion: A trans-esophageal echocardiography study.

    PubMed

    Kim, Yun Gi; Choi, Jong-Il; Kim, Mi-Na; Cho, Dong-Hyuk; Oh, Suk-Kyu; Kook, Hyungdon; Park, Hee-Soon; Lee, Kwang No; Baek, Yong-Soo; Roh, Seung-Young; Shim, Jaemin; Park, Seong-Mi; Shim, Wan Joo; Kim, Young-Hoon

    2018-01-01

    Spontaneous echo-contrast (SEC) and thrombus observed in trans-esophageal echocardiography (TEE) is known as a strong surrogate marker for future risk of ischemic stroke in patients with atrial fibrillation (AF) or atrial flutter (AFL). The efficacy of non-vitamin K antagonist oral anticoagulants (NOAC) compared to warfarin to prevent SEC or thrombus in patients with AF or AFL is currently unknown. AF or AFL patients who underwent direct current cardioversion (DCCV) and pre-DCCV TEE evaluation from January 2014 to October 2016 in a single center were analyzed. The prevalence of SEC and thrombus were compared between patients who received NOAC and those who took warfarin. NOAC included direct thrombin inhibitor and factor Xa inhibitors. Among 1,050 patients who were considered for DCCV, 424 patients anticoagulated with warfarin or NOAC underwent TEE prior to DCCV. Eighty patients who were anticoagulated for less than 21 days were excluded. Finally, 344 patients were included for the analysis (180 warfarin users vs. 164 NOAC users). No significant difference in the prevalence of SEC (44.4% vs. 43.9%; p = 0.919), dense SEC (13.9% vs. 15.2%; p = 0.722), or thrombus (2.2% vs. 4.3%; p = 0.281) was observed between the warfarin group and the NOAC group. In multivariate analysis, there was no association between NOAC and risk of SEC (odds ratio [OR]: 1.4, 95% CI: 0.796-2.297, p = 0.265) or thrombus (OR: 3.4, 95% CI: 0.726-16.039, p = 0.120). In conclusion, effectiveness of NOAC is comparable to warfarin in preventing SEC and thrombus in patients with AF or AFL undergoing DCCV. However, numerical increase in the prevalence of thrombus in NOAC group warrants further evaluation.

  13. Non-vitamin K antagonist oral anticoagulants versus warfarin for the prevention of spontaneous echo-contrast and thrombus in patients with atrial fibrillation or flutter undergoing cardioversion: A trans-esophageal echocardiography study

    PubMed Central

    Kim, Yun Gi; Kim, Mi-Na; Cho, Dong-Hyuk; Oh, Suk-Kyu; Kook, Hyungdon; Park, Hee-Soon; Lee, Kwang No; Baek, Yong-Soo; Roh, Seung-Young; Shim, Jaemin; Park, Seong-Mi; Shim, Wan Joo; Kim, Young-Hoon

    2018-01-01

    Spontaneous echo-contrast (SEC) and thrombus observed in trans-esophageal echocardiography (TEE) is known as a strong surrogate marker for future risk of ischemic stroke in patients with atrial fibrillation (AF) or atrial flutter (AFL). The efficacy of non-vitamin K antagonist oral anticoagulants (NOAC) compared to warfarin to prevent SEC or thrombus in patients with AF or AFL is currently unknown. AF or AFL patients who underwent direct current cardioversion (DCCV) and pre-DCCV TEE evaluation from January 2014 to October 2016 in a single center were analyzed. The prevalence of SEC and thrombus were compared between patients who received NOAC and those who took warfarin. NOAC included direct thrombin inhibitor and factor Xa inhibitors. Among 1,050 patients who were considered for DCCV, 424 patients anticoagulated with warfarin or NOAC underwent TEE prior to DCCV. Eighty patients who were anticoagulated for less than 21 days were excluded. Finally, 344 patients were included for the analysis (180 warfarin users vs. 164 NOAC users). No significant difference in the prevalence of SEC (44.4% vs. 43.9%; p = 0.919), dense SEC (13.9% vs. 15.2%; p = 0.722), or thrombus (2.2% vs. 4.3%; p = 0.281) was observed between the warfarin group and the NOAC group. In multivariate analysis, there was no association between NOAC and risk of SEC (odds ratio [OR]: 1.4, 95% CI: 0.796–2.297, p = 0.265) or thrombus (OR: 3.4, 95% CI: 0.726–16.039, p = 0.120). In conclusion, effectiveness of NOAC is comparable to warfarin in preventing SEC and thrombus in patients with AF or AFL undergoing DCCV. However, numerical increase in the prevalence of thrombus in NOAC group warrants further evaluation. PMID:29360845

  14. Low concentrations of Al(III) accelerate the formation of biofilm: Multiple effects of hormesis and flocculation.

    PubMed

    Cui, Xiaochun; Huo, Mingxin; Chen, Congli; Yu, Zhisen; Zhou, Chen; Li, Anran; Qiao, Bingqian; Zhou, Dandan; Crittenden, John C

    2018-09-01

    Residual Al(III) (at low concentration) is common in water treatment plants (WTPs) and is associated with bacteria. We hypothesize that Al(III) accelerate biofouling due to its hydrolysis and hormesis characteristics, as compared with other cations. To verify this, we elaborated the roles of Al(III) at low concentrations on the biofilm formation. Al(III) hormesis (<2.0mg/L) stimulated bacteria growth increased by ~3.7 times, and extracellular polymeric substances production also enhanced. Al(III) flocculation resulted in the suspended cells precipitation instantly, for Al(III) dosages of 0.6 and 2.0mg/L and the concentration of Al(III) decreased by 0.07 and 0.14mg/L, respectively. Al(III) poisoned the bridged bacterial cells and decreased their ATP by 22.36% and 55.91%, respectively. Al(III) formed polymer presented strong affinity with bacterial outer membrane, and this damaged the bacterial outer membrane. This caused proteins to leak at the combined point. Al-polymer bound to NH 2 and/or NH on the leaked protein, contributed to biofilm formation. Biofilm maturity was aided by polysaccharides, which shielded Al(III) toxicity for the formed biofilm. Thus, the biofilm exhibited a distinguished double-layer microstructure, principally with proteins and inactivated cells at the bottom, polysaccharides and activated cells at the top. Thus, hormesis and flocculation caused by low concentration Al(III) mutually promoted each other, and together accelerated biofilm formation. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Influence of manual thrombus aspiration on left ventricular diastolic function in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention.

    PubMed

    Ilić, Ivan; Stanković, Ivan; Vidaković, Radosav; Janićijević, Aleksandra; Cerović, Milivoje; Jovanović, Vladimir; Aleksić, Aleksandar; Obradović, Gojko; Nikolajević, Ivica; Kafedzić, Srdjan; Milicević, Dusan; Kusić, Jovana; Putniković, Biljana; Nesković, Aleksandar N

    2016-01-01

    Data on effects of thrombus aspiration on left ventricular diastolic function in ST-elevation myocardial infarction (STEMI) population are scarce. We sought to compare echocardiographic indices of the diastolic function and outcomes in STEMI patients treated with and without manual thrombus aspiration, in an academic, high-volume percutaneous coronary intervention (PCI) center. A total of 433 consecutive patients who underwent primary PCI in 2011-2012 were enrolled in the study. Patients were not eligible for the study if they already suffered a myocardial infarction, had been previously revascularized, received thrombolytics, presented with cardiogenic shock, had significant valvular disease, atrial fibrillation or had previously implanted pacemaker. Comprehensive echocardiogram was performed within 48 hours. During follow-up patients'status was assessed by an office visit or telephone interview. Patients treated with thrombus aspiration (TA+, n=216) had similar baseline characteristics as those without thrombus aspiration (TA-, n = 217). Groups had similar total ischemic time (319 ± 276 vs. 333 ± 372 min; p = 0.665), but TA+ group had higher maximum values of troponin I (39.5 ± 30.5 vs. 27.6 ± 26.9 ng/ml; p < 0.001). The echocardiography revealed similar left ventricular volumes and systolic function, but TA+ group had significantly higher incidence of E/e' > 15, as a marker of severe diastolic dysfunction' (TA+ 23.1% vs. TA- 15.2%; p = 0.050). During average follow-up of 14 ± 5 months, major adverse cardiac/cerebral events occurred at the similar rate (log rank p = 0.867). Thrombus aspiration is associated with a greater incidence of severe diastolic dysfunction in unselected STEMI patients treated with primary PCI, but it doesn't influence the incidence of major adverse cardiovascular events.

  16. Endosomal Redox Signaling in the Antiphospholipid Syndrome.

    PubMed

    Lackner, Karl J; Manukyan, Davit; Müller-Calleja, Nadine

    2017-04-01

    It is well established that the antiphospholipid syndrome (APS) is caused by antiphospholipid antibodies (aPL). While several underlying mechanisms have been described in the past, many open questions remain. Here, we will review data on endosomal signaling and, in particular, redox signaling in APS. Endosomal redox signaling has been implicated in several cellular processes including signaling of proinflammatory cytokines. We have shown that certain aPL can activate endosomal NADPH-oxidase (NOX) in several cell types followed by induction of proinflammatory and procoagulant cellular responses in vitro. Involvement of endosomes in aPL signaling has also been reported by others. In wild-type mice but not in NOX-deficient mice, aPL accelerate venous thrombus formation underscoring the relevance of endosomal NOX. Furthermore, hydroxychloroquine (HCQ) inhibits activation of endosomal NOX and prevents thrombus formation in aPL-treated mice. Endosomal redox signaling is an important novel mechanism involved in APS pathogenesis. This makes endosomes a potential target for future treatment approaches of APS.

  17. Nattokinase improves blood flow by inhibiting platelet aggregation and thrombus formation.

    PubMed

    Jang, Ja-Young; Kim, Tae-Su; Cai, Jingmei; Kim, Jihyun; Kim, Youngeun; Shin, Kyungha; Kim, Kwang Sei; Park, Sung Kyeong; Lee, Sung-Pyo; Choi, Ehn-Kyoung; Rhee, Man Hee; Kim, Yun-Bae

    2013-12-01

    The effects of nattokinase on the in vitro platelet aggregation and in vivo thrombosis were investigated in comparison with aspirin. Rabbit platelet-rich plasma was incubated with nattokinase and aggregation inducers collagen and thrombin, and the platelet aggregation rate was analyzed. Nattokinase significantly inhibited both the collagen- and thrombin-induced platelet aggregations. Nattokinase also reduced thromboxane B2 formation from collagen-activated platelets in a concentration-dependent manner. Rats were orally administered with nattokinase for 1 week, and their carotid arteries were exposed. Arterial thrombosis was induced by applying 35% FeCl3-soaked filter paper for 10 min, and the blood flow was monitored with a laser Doppler probe. Nattokinase delayed the FeCl3-induced arterial occlusion in a dose-dependent manner, doubling the occlusion time at 160 mg/kg. In addition, a high dose (500 mg/kg) of nattokinase fully prevented the occlusion, as achieved with aspirin (30 mg/kg). The results indicate that nattokinase extracted from fermented soybean inhibit platelet aggregation by blocking thromboxane formation, and thereby delay thrombosis following oxidative arterial wall injury. Therefore, it is suggested that nattokinase could be a good candidate without adverse effects for the improvement of blood flow.

  18. Current sheet Formation in a Conical Theta Pinch Faraday Accelerator with Radio-Frequency Assisted Discharge

    NASA Technical Reports Server (NTRS)

    Hallock, Ashley K.; Choueiri, Edgar Y.; Polzin, Kurt A.

    2007-01-01

    The inductive formation of current sheets in a conical theta pinch FARAD (Faraday Accelerator with Radio-frequency Assisted Discharge) thruster is investigated experimentally with time-integrated photography. The goal is to help in understanding the mechanisms and conditions controlling the strength and extent of the current sheet, which are two indices important for FARAD as a propulsion concept. The profiles of these two indices along the inside walls of the conical acceleration coil are assumed to be related to the profiles of the strength and extent of the luminosity pattern derived from photographs of the discharge. The variations of these profiles as a function of uniform back-fill neutral pressure (with no background magnetic field and all parameters held constant) provided the first clues on the nature and qualitative dependencies of current sheet formation. It was found that there is an optimal pressure for which both indices reach a maximum and that the rate of change in these indices with pressure differs on either side of this optimal pressure. This allowed the inference that current sheet formation follows a Townsend-like breakdown mechanism modified by the existence of a finite pressure-dependent radio-frequency-generated electron density background. The observation that the effective location of the luminosity pattern favors the exit-half of the conical coil is explained as the result of the tendency of the inductive discharge circuit to operate near its minimal self-inductance. Movement of the peak in the luminosity pattern towards the upstream side of the cone with increasing pressure is believed to result from the need of the circuit to compensate for the increase in background plasma resistivity due to increasing pressure.

  19. Nattokinase improves blood flow by inhibiting platelet aggregation and thrombus formation

    PubMed Central

    Jang, Ja-Young; Kim, Tae-Su; Cai, Jingmei; Kim, Jihyun; Kim, Youngeun; Shin, Kyungha; Kim, Kwang Sei; Park, Sung Kyeong; Lee, Sung-Pyo; Choi, Ehn-Kyoung

    2013-01-01

    The effects of nattokinase on the in vitro platelet aggregation and in vivo thrombosis were investigated in comparison with aspirin. Rabbit platelet-rich plasma was incubated with nattokinase and aggregation inducers collagen and thrombin, and the platelet aggregation rate was analyzed. Nattokinase significantly inhibited both the collagen- and thrombin-induced platelet aggregations. Nattokinase also reduced thromboxane B2 formation from collagen-activated platelets in a concentration-dependent manner. Rats were orally administered with nattokinase for 1 week, and their carotid arteries were exposed. Arterial thrombosis was induced by applying 35% FeCl3-soaked filter paper for 10 min, and the blood flow was monitored with a laser Doppler probe. Nattokinase delayed the FeCl3-induced arterial occlusion in a dose-dependent manner, doubling the occlusion time at 160 mg/kg. In addition, a high dose (500 mg/kg) of nattokinase fully prevented the occlusion, as achieved with aspirin (30 mg/kg). The results indicate that nattokinase extracted from fermented soybean inhibit platelet aggregation by blocking thromboxane formation, and thereby delay thrombosis following oxidative arterial wall injury. Therefore, it is suggested that nattokinase could be a good candidate without adverse effects for the improvement of blood flow. PMID:24396387

  20. Short-Term Anticoagulant Therapy and Thrombus Location Are Independent Risk Factors for Delayed Recanalization of Deep Vein Thrombosis.

    PubMed

    Zhang, Chuanlin; Fu, Qining; Zhao, Yu; Mu, Shaoyu; Liu, Liping

    2016-01-21

    Prompt recanalization of the vein containing the thrombus is an important goal during the initial treatment of DVT, and risk factors for delayed recanalization in patients with deep vein thrombosis (DVT) in the lower extremities need to be determined. A total of 174 patients with DVT in lower extremities were recruited from June 2014 to March 2015 at our hospital. Duplex ultrasound scanning was conducted for all patients at 1 and 6 months after baseline evaluation. We divided the patients into recanalization and non-recanalization groups and analyzed risk factors for delayed recanalization. The univariate analysis revealed that an oral anticoagulant time of less than 3 months and venous thrombus location were risk factors for delayed recanalization (P<0.01). However, age, gender, hypertension, diabetes, pulmonary embolism, incidence factors, the use of catheter-directed thrombolytic (CDT) drugs, and inferior vena cava filter (IVCF) implantation had no influence on the incidence of delayed recanalization in patients with DVT (P>0.05). The multivariate analysis showed that patients with an anticoagulant time of less than 3 months had a lower incidence of recanalization than those with an anticoagulant time of more than 3 months (OR=2.358, P<0.05). The risk of delayed recanalization in patients with proximal DVT was 7 times higher than that in patients with distal DVT. Duration of anticoagulant treatment of less than 3 months and venous thrombus location are independent risk factors for delayed recanalization of DVT in the lower extremities.

  1. Simplagrin, a Platelet Aggregation Inhibitor from Simulium nigrimanum Salivary Glands Specifically Binds to the Von Willebrand Factor Receptor in Collagen and Inhibits Carotid Thrombus Formation In Vivo

    PubMed Central

    Chagas, Andrezza C.; McPhie, Peter; San, Hong; Narum, David; Reiter, Karine; Tokomasu, Fuyuki; Brayner, Fabio A.; Alves, Luiz C.; Ribeiro, José M. C.; Calvo, Eric

    2014-01-01

    Background Among the several challenges faced by bloodsucking arthropods, the vertebrate hemostatic response against blood loss represents an important barrier to efficient blood feeding. Here we report the first inhibitor of collagen-induced platelet aggregation derived from the salivary glands of a black fly (Simulium nigrimanum), named Simplagrin. Methods and Findings Simplagrin was expressed in mammalian cells and purified by affinity-and size-exclusion chromatography. Light-scattering studies showed that Simplagrin has an elongated monomeric form with a hydrodynamic radius of 5.6 nm. Simplagrin binds to collagen (type I-VI) with high affinity (2–15 nM), and this interaction does not involve any significant conformational change as determined by circular dichroism spectroscopy. Simplagrin-collagen interaction is both entropically and enthalpically driven with a large negative ΔG, indicating that this interaction is favorable and occurs spontaneously. Simplagrin specifically inhibits von Willebrand factor interaction with collagen type III and completely blocks platelet adhesion to collagen under flow conditions at high shear rates; however, Simplagrin failed to block glycoprotein VI and Iα2β1 interaction to collagen. Simplagrin binds to RGQOGVMGF peptide with an affinity (KD 11 nM) similar to that of Simplagrin for collagen. Furthermore, Simplagrin prevents laser-induced carotid thrombus formation in vivo without significant bleeding in mice and could be useful as an antithrombotic agent in thrombosis related disease. Conclusion Our results support the orthology of the Aegyptin clade in bloodsucking Nematocera and the hypothesis of a faster evolutionary rate of salivary function of proteins from blood feeding arthropods. PMID:24921659

  2. Laser Accelerator

    DTIC Science & Technology

    2014-09-01

    hollow metal sphere. Voltages of over 10 MV can be reached if used with an insulating gas. Corona discharge limits all electrostatic accelerators to...laser field. Lasers can have strong electric fields with frequencies high enough to avoid corona formation and break- down. The key is to couple the...leading to a spark discharge in the accelerator and thus a breakdown of the electrostatic field [6], [7]. Figure 1.1: Cockroft-Walton cascade generator

  3. Multimodal Molecular Imaging Reveals High Target Uptake and Specificity of 111In- and 68Ga-Labeled Fibrin-Binding Probes for Thrombus Detection in Rats.

    PubMed

    Oliveira, Bruno L; Blasi, Francesco; Rietz, Tyson A; Rotile, Nicholas J; Day, Helen; Caravan, Peter

    2015-10-01

    We recently showed the high target specificity and favorable imaging properties of 64Cu and Al18F PET probes for noninvasive imaging of thrombosis. Here, our aim was to evaluate new derivatives labeled with either with 68Ga, 111In, or 99mTc as thrombus imaging agents for PET and SPECT. In this study, the feasibility and potential of these probes for thrombus imaging was assessed in detail in 2 animal models of arterial thrombosis. The specificity of the probes was further evaluated using a triple-isotope approach with multimodal SPECT/PET/CT imaging. Radiotracers were synthesized using a known fibrin-binding peptide conjugated to 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid monoamide (DOTA-MA), or a diethylenetriamine ligand (DETA-propanoic acid [PA]), followed by labeling with 68Ga (FBP14, 68Ga-NODAGA), 111In (FBP15, 111In-DOTA-MA), or 99mTc (FBP16, 99mTc(CO)3-DETA-PA), respectively. PET or SPECT imaging, biodistribution, pharmacokinetics, and metabolic stability were evaluated in rat models of mural and occlusive carotid artery thrombosis. In vivo target specificity was evaluated by comparing the distribution of the SPECT and PET probes with preformed 125I-labeled thrombi and with a nonbinding control probe using SPECT/PET/CT imaging. All 3 radiotracers showed affinity similar to soluble fibrin fragment DD(E) (inhibition constant=0.53-0.83 μM). After the kidneys, the highest uptake of 68Ga-FBP14 and 111In-FBP15 was in the thrombus (1.0±0.2 percentage injected dose per gram), with low off-target accumulation. Both radiotracers underwent fast systemic elimination (half-life, 8-15 min) through the kidneys, which led to highly conspicuous thrombi on PET and SPECT images. 99mTc-FBP16 displayed low target uptake and distribution consistent with aggregation or degradation. Triple-isotope imaging experiments showed that both 68Ga-FBP14 and 111In-FBP15, but not the nonbinding derivative 64Cu

  4. Multimodal molecular imaging reveals high target uptake and specificity of 111In and 68Ga labeled fibrin-binding probes for thrombus detection in rats

    PubMed Central

    Oliveira, Bruno L.; Blasi, Francesco; Rietz, Tyson A.; Rotile, Nicholas J.; Day, Helen; Caravan, Peter

    2016-01-01

    We recently showed the high target specificity and favorable imaging properties of 64Cu and Al18F positron emission tomography (PET) probes for non-invasive imaging of thrombosis. Here, our aim was to evaluate new derivatives labeled with either with 68Ga, 111In, or 99mTc as thrombus imaging agents for PET and single-photon emission computed tomography (SPECT). In this study, the feasibility and potential of these probes for thrombus imaging was assessed in detail in two animal models of arterial thrombosis. The specificity of the probes was further evaluated using a triple-isotope approach with multimodal SPECT/PET/CT imaging. Methods Radiotracers were synthesized using a known fibrin-binding peptide conjugated to NODAGA, DOTA-MA, or a diethylenetriamine ligand (DETA-PA), followed by labeling with 68Ga (FBP14, 68Ga-NODAGA), 111In (FBP15, 111In-DOTA-MA) or 99mTc (FBP16, 99mTc(CO)3-DETA-PA), respectively. PET or SPECT imaging, biodistribution, pharmacokinetics and metabolic stability were evaluated in rat models of mural and occlusive carotid artery thrombosis. In vivo target specificity was evaluated by comparing the distribution of the SPECT and PET probes with preformed 125I-labeled thrombi and with a non-binding control probe using SPECT/PET/CT imaging. Results All three radiotracers showed similar affinity to soluble fibrin fragment DD(E) (Ki = 0.53–0.83 μM). After the kidneys, the highest uptake of 68Ga-FBP14 and 111In-FBP15 was in the thrombus (1.0 ± 0.2% ID/g) with low off-target accumulation. Both radiotracers underwent fast systemic elimination (t1/2 = 8-15 min) through the kidneys, which led to highly conspicuous thrombi on PET and SPECT images. 99mTc-FBP16 displayed low target uptake and distribution consistent with aggregation and/or degradation. Triple isotope imaging experiments showed that both 68Ga-FBP14 and 111In-FBP15, but not the nonbinding derivative 64Cu-D-Cys-FBP8, detected the location of the 125I-labeled thrombus, confirming high target

  5. Formate generated by cellular oxidation of formaldehyde accelerates the glycolytic flux in cultured astrocytes.

    PubMed

    Tulpule, Ketki; Dringen, Ralf

    2012-04-01

    Formaldehyde is a neurotoxic compound that can be endogenously generated in the brain. Because astrocytes play a key role in metabolism and detoxification processes in brain, we have investigated the capacity of these cells to metabolize formaldehyde using primary astrocyte-rich cultures as a model system. Application of formaldehyde to these cultures resulted in the appearance of formate in cells and in a time-, concentration- and temperature-dependent disappearance of formaldehyde from the medium that was accompanied by a matching extracellular accumulation of formate. This formaldehyde-oxidizing capacity of astrocyte cultures is likely to be catalyzed by alcohol dehydrogenase 3 and aldehyde dehydrogenase 2, because the cells of the cultures contain the mRNAs of these formaldehyde-oxidizing enzymes. In addition, exposure to formaldehyde increased both glucose consumption and lactate production by the cells. Both the strong increase in the cellular formate content and the increase in glycolytic flux were only observed after application of formaldehyde to the cells, but not after treatment with exogenous methanol or formate. The accelerated lactate production was not additive to that obtained for azide, a known inhibitor of complex IV of the respiratory chain, and persisted after removal of formaldehyde after a formaldehyde exposure for 1.5 h. These data demonstrate that cultured astrocytes efficiently oxidize formaldehyde to formate, which subsequently enhances glycolytic flux, most likely by inhibition of mitochondrial respiration. Copyright © 2012 Wiley Periodicals, Inc.

  6. Formation of Glass with Embedded Metal and Sulfides from Shock-accelerated Crystalline Dust in Superbubbles

    NASA Astrophysics Data System (ADS)

    Westphal, A. J.; Bradley, J. P.

    2004-12-01

    Interplanetary dust particles (IDPs) contain enigmatic submicron components called GEMS (glass with embedded metal and sulfides). The compositions and structures of GEMS indicate that they have been processed by exposure to ionizing radiation, but details of the actual irradiation environment(s) have remained elusive. Here we propose a mechanism and astrophysical site for GEMS formation that explains for the first time the following key properties of GEMS: they are stoichiometrically enriched in oxygen and systematically depleted in S, Mg, Ca, and Fe (relative to solar abundances); most have normal (solar) oxygen isotopic compositions; they exhibit a strikingly narrow size distribution (0.1-0.5 μm diameter); and some of them contain ``relict'' crystals within their silicate glass matrices. We show that the compositions, size distribution, and survival of relict crystals are inconsistent with amorphization by particles accelerated by diffusive shock acceleration. Instead, we propose that GEMS are formed from crystalline grains that condense in stellar outflows from massive stars in OB associations, are accelerated in encounters with frequent supernova shocks inside the associated superbubble (SB), and are implanted with atoms from the hot gas in the SB interior. We thus reverse the usual roles of target and projectile. Rather than being bombarded at rest by energetic ions, grains are accelerated and bombarded by a nearly monovelocity beam of atoms as viewed in their rest frame. Meyer, Drury, and Ellison have proposed that Galactic cosmic rays (GCRs) originate from ions sputtered from such accelerated dust grains. We suggest that GEMS are surviving members of a population of fast grains that constitute the long-sought source material for GCRs. Thus, representatives of the GCR source material may have been awaiting discovery in cosmic dust labs for the last 30 yr.

  7. A case of a large Chiari network mimicking a right atrial thrombus.

    PubMed

    Erdogan, Sevinc Bayer; Akansel, Serdar; Sargın, Murat; Mete, Muge Evren Tasdemir; Arslanhan, Gokhan; Aka, Serap Aykut

    2017-01-01

    The Chiari network is described as a reticulated network of fibers connected to the Eustachian valve identified as the embryological remnant of the right valve of the sinus venosus. It is an incidental finding without any significant pathophysiological consequences. However, the presence of the Chiari network in the right atrium obliges the physician to differentiate from other right atrial pathologies. We present a case of a large Chiari network mimicking a right atrial thrombus with incidental finding in a 76-year-old man undergoing coronary artery bypass surgery.

  8. Prenatal lead exposure is associated with decreased cord blood DNA methylation of the glycoprotein VI gene involved in platelet activation and thrombus formation

    PubMed Central

    Engström, Karin; Rydbeck, Filip; Kippler, Maria; Wojdacz, Tomasz K.; Arifeen, Shams; Vahter, Marie; Broberg, Karin

    2015-01-01

    Abstract Early-life lead exposure impairs neurodevelopment and later exposure affects the cardiovascular system. Lead has been associated with reduced global 5-methylcytosine DNA methylation, suggesting that lead toxicity acts through epigenetic mechanisms. The objective of this study is to clarify how early-life lead exposure alters DNA methylation of specific genes, using an epigenomic approach. We measured lead concentrations in urine [gestational week (GW), 8] and erythrocytes (GW 14), using inductively coupled plasma mass spectrometry, for 127 pregnant mothers recruited in the MINIMat food and supplementation cohort in rural Bangladesh. Cord blood DNA methylation was analyzed with the Infinium HumanMethylation450K BeadChip, and top sites were validated by methylation-sensitive high-resolution melt curve analysis. Maternal urinary lead concentrations (divided into quartiles) showed significant (after adjustment for false discovery rate) inverse associations with methylation at nine CpGs. Three of these sites were in the 5′-end, including the promoter, of glycoprotein IV (GP6); cg18355337 (q = 0.029, β = −0.30), cg25818583 (q = 0.041, β = −0.18), and cg23796967 (q = 0.047, β = −0.17). The methylation in another CpG site in GP6 was close to significant (cg05374025, q = 0.057, β = − 0.23). The erythrocyte lead concentrations (divided into quartiles) were also inversely associated with CpG methylation in GP6, although this was not statistically significant after false discovery rate adjustments. Eight CpG sites in GP6 constituted a differentially methylated region in relation to urinary lead (P = 0.005, q = 0.48) and erythrocyte lead (P = 0.007, q = 0.46). In conclusion, we found that moderate prenatal lead exposure appears to epigenetically affect GP6, a key component of platelet aggregation and thrombus formation, suggesting a novel link between early lead exposure and cardiovascular disease later in

  9. Mechanisms by which thrombolytic therapy results in nonuniform lysis and residual thrombus after reperfusion.

    PubMed

    Anand, S; Kudallur, V; Pitman, E B; Diamond, S L

    1997-01-01

    A transport-reaction model describing penetration of plasmin by diffusion and permeation into a dissolving fibrin gel was solved numerically to explore mechanisms that lead to the formation and growth of dissolution fingers through blood clots during thrombolytic therapy. Under conditions of fluid permeation driven by arterial pressures, small random spatial variations in the initial fibrin density within clots (+/-4 to 25% peak variations) were predicted by the simulation to result in dramatic dissolution fingers that grew in time. With in vitro experiments, video microscopy revealed that the shape of the proximal face of a fibrin gel, when deformed by pressure-driven permeation, led to lytic breakthrough in the center of the clot, consistent with model predictions of increased velocities in this region leading to cannulation. Computer simulation of lysis of fibrin retracted by platelets (where more permeable regions are expected in the middle of the clot due to retraction) predicted cannulation of the clot during thrombolysis. This residual, annular thrombus was predicted to lyse more slowly, because radial pressure gradients to drive inner clot permeation were quite small. In conjunction with kinetic models of systemic pharmacodynamics and plasminogen activation biochemistry, a two-dimensional transport-reaction model can facilitate the prediction of the time and causes of clot cannulation, poor reperfusion, and embolism during thrombolysis.

  10. Tissue factor levels and the fibrinolytic system in thin and thick intraluminal thrombus and underlying walls of abdominal aortic aneurysms.

    PubMed

    Siennicka, Aldona; Zuchowski, Marta; Kaczmarczyk, Mariusz; Cnotliwy, Miłosław; Clark, Jeremy Simon; Jastrzębska, Maria

    2018-03-20

    The hemostatic system cooperates with proteolytic degradation in processes allowing abdominal aortic aneurysm (AAA) formation. In previous studies, it has been suggested that aneurysm rupture depends on intraluminal thrombus (ILT) thickness, which varies across each individual aneurysm. We hypothesized that hemostatic components differentially accumulate in AAA tissue in relation to ILT thickness. Thick (A1) and thin (B1) segments of ILTs and aneurysm wall sections A (adjacent to A1) and B (adjacent to B1) from one aneurysm sac were taken from 35 patients undergoing elective repair. Factor levels were measured using enzyme-linked immunosorbent assay of protein extract. Tissue factor (TF) activities were significantly higher in thinner segments of AAA (B1 vs A1, P = .003; B vs A, P < .001; B vs A1, P < .001; B vs B1, P = .001). Significantly higher tissue plasminogen activator was found in thick thrombus-covered wall segments (A) than in B, A1, and B1 (P = .015, P < .001, and P < .001, respectively). Plasminogen concentrations were highest in ILT. Concentrations of α 2 -antiplasmin in thin ILT adjacent walls (B) were higher compared with wall (A) adjacent to thick ILT (P = .021) and thick ILT (A1; P < .001). Significant correlations between levels of different factors were mostly found in thick ILT (A1). However, no correlations were found at B sites, except for a correlation between plasmin and TF activities (r = 0.55; P = .004). These results suggest that higher TF activities are present in thinner AAA regions. These parameters and local fibrinolysis may be part of the processes leading to destruction of the aneurysm wall. Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  11. Extraluminal venous interruption for free-floating thrombus in the deep veins of lower limbs.

    PubMed

    Casian, D; Gutsu, E; Culiuc, V

    2010-01-01

    The free-floating thrombus (FFT) represents a particular form of deep vein thrombosis with extremely high potential of fatal pulmonary embolism. The purpose of the study was to evaluate the early results of aggressive surgical approach to FFT. During the period 2005-2008 years FFT was diagnosed in 13 patients. Demographic characteristics of patients: medium age--54.7 years, male--76.9%, significant comorbidity--5 (38.5%) cases. Localization of FFT: superficial femoral vein (SFV)--5 (38.5%), common femoral vein (CFV)--4 (30.7%), external iliac vein (EIV)--2 (15.4%), inferior cava vein (ICV)--2 (15.4%). Manifestations of previous pulmonary embolism were documented preoperatively in 3 (23.1%) cases. The following emergency surgical procedures were performed: ligation--3 (23.1%) or plication--2 (15.4%) of SFV; plication of CFV--5 (38.5%) patients, combined in 4 cases with partial thrombectomy (free-floating part of thrombus); plication of common iliac vein--1 (7.6%); plication of ICV--2 (15.4%) cases. Primary or recurrent cases of clinically significant pulmonary embolism were not detected in the postoperative period. The accumulated experience of surgical management of patients with FFT reveals the important role of deep vein ligation/plication in prevention of fatal pulmonary embolism.

  12. Short-Term Anticoagulant Therapy and Thrombus Location Are Independent Risk Factors for Delayed Recanalization of Deep Vein Thrombosis

    PubMed Central

    Zhang, Chuanlin; Fu, Qining; Zhao, Yu; Mu, Shaoyu; Liu, Liping

    2016-01-01

    Background Prompt recanalization of the vein containing the thrombus is an important goal during the initial treatment of DVT, and risk factors for delayed recanalization in patients with deep vein thrombosis (DVT) in the lower extremities need to be determined. Material/Methods A total of 174 patients with DVT in lower extremities were recruited from June 2014 to March 2015 at our hospital. Duplex ultrasound scanning was conducted for all patients at 1 and 6 months after baseline evaluation. We divided the patients into recanalization and non-recanalization groups and analyzed risk factors for delayed recanalization. Results The univariate analysis revealed that an oral anticoagulant time of less than 3 months and venous thrombus location were risk factors for delayed recanalization (P<0.01). However, age, gender, hypertension, diabetes, pulmonary embolism, incidence factors, the use of catheter-directed thrombolytic (CDT) drugs, and inferior vena cava filter (IVCF) implantation had no influence on the incidence of delayed recanalization in patients with DVT (P>0.05). The multivariate analysis showed that patients with an anticoagulant time of less than 3 months had a lower incidence of recanalization than those with an anticoagulant time of more than 3 months (OR=2.358, P<0.05). The risk of delayed recanalization in patients with proximal DVT was 7 times higher than that in patients with distal DVT. Conclusions Duration of anticoagulant treatment of less than 3 months and venous thrombus location are independent risk factors for delayed recanalization of DVT in the lower extremities. PMID:26790571

  13. Echocardiographic assessment with right ventricular function improvement following ultrasound-accelerated catheter-directed thrombolytic therapy in submassive pulmonary embolism.

    PubMed

    Doheny, Charles; Gonzalez, Lorena; Duchman, Stanley M; Varon, Joseph; Bechara, Carlos F; Cheung, Mathew; Lin, Peter H

    2018-06-01

    Introduction The objective of this study was to evaluate the efficacy of ultrasound-accelerated catheter-directed thrombolytic therapy in patients with submassive pulmonary embolism. Methods Clinical records of 46 patients with submassive pulmonary embolism who underwent ultrasound-accelerated catheter-directed pulmonary thrombolysis using tissue plasminogen activator, from 2007 to 2017, were analyzed. All patients experienced clinical symptoms with computed tomography evidence of pulmonary thrombus burden. Right ventricular dysfunction was present in all patients by echocardiographic finding of right ventricle-to-left ventricle ratio > 0.9. Treatment outcome, procedural complications, right ventricular pressures, and thrombus clearance were evaluated. Follow-up evaluation included echocardiographic assessment of right ventricle-to-left ventricle ratio at one month, six months, and one year. Results Technical success was achieved in all patients ( n = 46, 100%). Our patients received an average of 18.4 ± 4.7 mg of tissue plasminogen activator using ultrasound-accelerated thrombolytic catheter with an average infusion time of 16.5± 5.4 h. Clinical success was achieved in all patients (100%). Significant reduction of mean pulmonary artery pressure occurred following the treatment, which decreased from 36 ± 8 to 21 ± 5 mmHg ( p < 0.001). There were no major bleeding complications. All-cause mortality at 30 days was 0%. No patient developed recurrent pulmonary embolism during follow-up. During the follow-up period, 43 patients (93%) showed improvement of right ventricular dysfunction based on echocardiographic assessment. The right ventricle-to-left ventricle ratio decreased from 1.32 ± 0.18 to 0.91 ± 0.13 at the time of hospital discharge ( p < 0.01). The right ventricular function remained improved at 6 months and 12 months of follow-up, as right ventricle-to-left ventricle ratio were 0.92 ± 0.14 ( p < 0.01) and 0

  14. PROTECT: PRoximal balloon Occlusion TogEther with direCt Thrombus aspiration during stent retriever thrombectomy - evaluation of a double embolic protection approach in endovascular stroke treatment.

    PubMed

    Maegerlein, Christian; Mönch, Sebastian; Boeckh-Behrens, Tobias; Lehm, Manuel; Hedderich, Dennis M; Berndt, Maria Teresa; Wunderlich, Silke; Zimmer, Claus; Kaesmacher, Johannes; Friedrich, Benjamin

    2017-12-08

    Stent retriever-based mechanical thrombectomy (MT) for emergent large vessel occlusions (ELVO) is often complicated by thrombus fragmentation causing distal embolization and embolization to new vascular territories. Well-established embolic protection approaches include proximal flow arrest and distal aspiration techniques during stent retriever maneuvers. Aiming at the reduction of thrombus fragmentation during MT we evaluated a technical approach combining proximal balloon occlusion together with direct thrombus aspiration during MT: the PROTECT technique. We performed a case-control study comparing the PROTECT technique with sole distal aspiration during MT regarding technical and procedural parameters, n=200 patients with ELVO of either the terminus of the internal carotid artery or the proximal middle artery were included. PROTECT resulted in a shorter procedure time (29 vs 40 min; P=0.002), in a higher rate of successful recanalizations (100% vs 78%; P=0.001) and a higher rate of complete reperfusions (70% vs 39%; P<0.001) compared with sole distal aspiration during MT. The PROTECT technique is a promising new approach to significantly reduce thrombus fragmentation and, hence distal embolization during MT. This safe and efficient technique needs to be validated in larger trials to confirm our results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  15. In Situ Investigation of a Self-Accelerated Cocrystal Formation by Grinding Pyrazinamide with Oxalic Acid.

    PubMed

    Kulla, Hannes; Greiser, Sebastian; Benemann, Sigrid; Rademann, Klaus; Emmerling, Franziska

    2016-07-14

    A new cocrystal of pyrazinamide with oxalic acid was prepared mechanochemically and characterized by PXRD, Raman spectroscopy, solid-state NMR spectroscopy, DTA-TG, and SEM. Based on powder X-ray diffraction data the structure was solved. The formation pathway of the reaction was studied in situ using combined synchrotron PXRD and Raman spectroscopy. Using oxalic acid dihydrate the initially neat grinding turned into a rapid self-accelerated liquid-assisted grinding process by the release of crystallization water. Under these conditions, the cocrystal was formed directly within two minutes.

  16. Rapid occurrence of left ventricular thrombus associated with platinum-based chemotherapy plus cetuximab for the treatment of metastatic squamous cell carcinoma of the head and neck: A case report.

    PubMed

    Ikeda, Atsushi; Yamachika, Eiki; Mizutani, Masahide; Matsubara, Masakazu; Moritani, Norifumi; Nakatsuji, Kazuki; Iida, Seiji

    2017-11-01

    Platinum-based chemotherapy plus cetuximab represents the first-line treatment for recurrent or metastatic squamous cell carcinoma of the head and neck. The most common adverse events associated with cetuximab are infusion reactions and skin reactions, and a risk of venous thromboembolic events has also recently been reported in association with cetuximab. It is well known that thrombosis is a common complication of malignancy, and represents the second most frequent cause of mortality in cancer patients. The present study reports the case of a 79-year-old man who presented with lung and liver metastases from tongue squamous cell carcinoma, for which platinum-based chemotherapy plus cetuximab was administered. After 1 cycle, the patient showed rapid growth of a left ventricular (LV) thrombus, despite ongoing antiplatelet therapy for an old myocardial infarction. Anticoagulant therapy was administered to treat the LV thrombus, which resolved within 1 week. To the best of our knowledge, this represents the first reported case of rapidly occurring LV thrombus associated with platinum-based chemotherapy plus cetuximab. Platinum-based chemotherapy plus cetuximab may be associated with a higher risk of embolic thrombus.

  17. Fluid displacement from intraluminal thrombus of abdominal aortic aneurysm as a result of uniform compression.

    PubMed

    van Noort, Kim; Schuurmann, Richte Cl; Wermelink, Bryan; Slump, Cornelis H; Kuijpers, Karel C; de Vries, Jean-Paul Pm

    2017-10-01

    Objectives The results after aneurysm repair with an endovascular aneurysm sealing (EVAS) system are dependent on the stability of the aneurysm sac and particularly the intraluminal abdominal aortic thrombus (ILT). The postprocedural ILT volume is decreased compared with preprocedural ILT volume in aortic aneurysm patients treated with EVAS. We hypothesize that ILT is not stable in all patients and pressurization of the ILT may result in displacement of fluids from the ILT, no differently than serum is displaced from whole blood when it settles. To date, the mechanism and quantification of fluid displacement from ILT are unknown. Methods The study included 21 patients who underwent elective open abdominal aortic aneurysm repair. The ILT was harvested as a routine procedure during the operation. After excision of a histologic sample of the ILT specimen in four patients, ILT volume was measured and the ILT was compressed in a dedicated compression setup designed to apply uniform compression of 200 mmHg for 5 min. After compression, the volumes of the remaining thrombus and the displaced fluid were measured. Results The median (interquartile-range) of ILT volume before compression was 60 (66) mL, and a median of 5.7 (8.4) mL of fluid was displaced from the ILT after compression, resulting in a median thrombus volume decrease of 11% (10%). Fluid components can be up to 31% of the entire ILT volume. Histologic examination of four ILT specimens showed a reduction of the medial layer of the ILT after compression, which was the result of compression of fluid-containing canaliculi. Conclusions Applying pressure of 200 mmHg to abdominal aortic aneurysm ILT resulted in the displacement of fluid, with a large variation among patients. Fluid displacement may result in decrease of ILT volume during and after EVAS, which might have implications on pre-EVAS volume planning and on stability of the endobags during follow-up which may lead to migration, endoleak or both.

  18. Identification and Management of Pump Thrombus in the HeartWare Left Ventricular Assist Device System: A Novel Approach Using Log File Analysis.

    PubMed

    Jorde, Ulrich P; Aaronson, Keith D; Najjar, Samer S; Pagani, Francis D; Hayward, Christopher; Zimpfer, Daniel; Schlöglhofer, Thomas; Pham, Duc T; Goldstein, Daniel J; Leadley, Katrin; Chow, Ming-Jay; Brown, Michael C; Uriel, Nir

    2015-11-01

    The study sought to characterize patterns in the HeartWare (HeartWare Inc., Framingham, Massachusetts) ventricular assist device (HVAD) log files associated with successful medical treatment of device thrombosis. Device thrombosis is a serious adverse event for mechanical circulatory support devices and is often preceded by increased power consumption. Log files of the pump power are easily accessible on the bedside monitor of HVAD patients and may allow early diagnosis of device thrombosis. Furthermore, analysis of the log files may be able to predict the success rate of thrombolysis or the need for pump exchange. The log files of 15 ADVANCE trial patients (algorithm derivation cohort) with 16 pump thrombus events treated with tissue plasminogen activator (tPA) were assessed for changes in the absolute and rate of increase in power consumption. Successful thrombolysis was defined as a clinical resolution of pump thrombus including normalization of power consumption and improvement in biochemical markers of hemolysis. Significant differences in log file patterns between successful and unsuccessful thrombolysis treatments were verified in 43 patients with 53 pump thrombus events implanted outside of clinical trials (validation cohort). The overall success rate of tPA therapy was 57%. Successful treatments had significantly lower measures of percent of expected power (130.9% vs. 196.1%, p = 0.016) and rate of increase in power (0.61 vs. 2.87, p < 0.0001). Medical therapy was successful in 77.7% of the algorithm development cohort and 81.3% of the validation cohort when the rate of power increase and percent of expected power values were <1.25% and 200%, respectively. Log file parameters can potentially predict the likelihood of successful tPA treatments and if validated prospectively, could substantially alter the approach to thrombus management. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  19. Simultaneous extraction of centerlines, stenosis, and thrombus detection in renal CT angiography

    NASA Astrophysics Data System (ADS)

    Subramanyan, Krishna; Durgan, Jacob; Hodgkiss, Thomas D.; Chandra, Shalabh

    2004-05-01

    The Renal Artery Stenosis (RAS) is the major cause of renovascular hypertension and CT angiography has shown tremendous promise as a noninvasive method for reliably detecting renal artery stenosis. The purpose of this study was to validate the semi-automated methods to assist in extraction of renal branches and characterizing the associated renal artery stenosis. Automatically computed diagnostic images such as straight MIP, curved MPR, cross-sections, and diameters from multi-slice CT are presented and evaluated for its acceptance. We used vessel-tracking image processing methods to extract the aortic-renal vessel tree in a CT data in axial slice images. Next, from the topology and anatomy of the aortic vessel tree, the stenosis, and thrombus section and branching of the renal arteries are extracted. The results are presented in curved MPR and continuously variable MIP images. In this study, 15 patients were scanned with contrast on Mx8000 CT scanner (Philips Medical Systems), with 1.0 mm thickness, 0.5mm slice spacing, and 120kVp and a stack of 512x512x150 volume sets were reconstructed. The automated image processing took less than 50 seconds to compute the centerline and borders of the aortic/renal vessel tree. The overall assessment of manual and automatically generated stenosis yielded a weighted kappa statistic of 0.97 at right renal arteries, 0.94 at the left renal branches. The thrombus region contoured manually and semi-automatically agreed upon at 0.93. The manual time to process each case is approximately 25 to 30 minutes.

  20. Influence of solidification accelerators on structure formation of anhydrite-containing binders

    NASA Astrophysics Data System (ADS)

    Anikanova, L.; Volkova, O.; Kudyakov, A.; Sarkisov, Y.; Tolstov, D.

    2016-01-01

    The article presents results of scientific analysis of chemical additives influence on acid fluoride binder. It was found that the influence of sulfate nature additives on the process of hydration and solidification of the binder is similar to influence of additives on indissoluble anhydrite. Additives with SO42- anion NO- are more efficient. The mentioned additives according to accelerating effect belong to the following succession: K2SO4 > Na2SO4 > FeSO4 > MgSO4. Facilitation of the process of hydration and solidification of the binder, increase in density and durability of the binder (32 MPa) is to the greatest extent achieved with the introduction of 2% sodium sulfate additive of the binder's mass into the composition of the binder along with the ultrasonic treatment of water solution. Directed crystal formation process with healing of porous structure by new growths presented as calcium sulfate dehydrate and hydroglauberite provides positive effect.

  1. Embolic attack in patients with atrial fibrillation and atrial thrombus depends on the character of the thrombus.

    PubMed

    Abe, Yukihiko; Asakura, Tukasa; Sakamoto, Nobuo; Ishikawa, Shunichi; Muroi, Syuichi; Saitoh, Fujiko; Satoh, Masahiko; Suzuki, Shigebumi; Ono, Masahiro; Sakabe, Atsushi; Iwai, Masumi; Sando, Masahito; Gotou, Jun; Watanabe, Yasuyuki; Nagata, Kenji; Maehara, Kazuhira; Maruyama, Yukio

    2003-03-01

    It is very important to prevent embolisms from left atrial thrombi (LAT). The present study was a trial for the management of patients with AT using 122 patients with atrial fibrillation and LAT who were followed for 1 year after transesophageal echocardiography. LAT were classified by their shape and mobility into the mobile ball type (MB, n=28), fixed ball type (FB, n=32) and mountain type (MO, n=42). The patients were given warfarin (INR: 1.5-2.0, n=43), aspirin 81 mg (n=74) and/or ticlopidine 200 mg/day (n=31). The embolic rate (ER) in the MB group was significantly higher than in the other groups [ie, MB 39.3% vs FB 15.6% (p<0.05), vs MO 2.4% (p<0.05)]. The ER in the FB group was significantly higher than in the MO group (p<0.05). Therapy with a combination of ticlopidine and aspirin reduced the ER in the patients with ball thrombi. The ER of the ball thrombus type group, especially the MB group, was very high in spite of therapy with anti-coagulants and/or anti-platelet agents, and such patients should be treated by early surgical intervention. However, the combination of ticlopidine and aspirin may be useful for preventing embolism.

  2. Roles of Transesophageal Echocardiography and Cardiac Computed Tomography for Evaluation of Left Atrial Thrombus and Associated Pathology: A Review and Critical Analysis.

    PubMed

    Pathan, Faraz; Hecht, Harvey; Narula, Jagat; Marwick, Thomas H

    2018-04-01

    Evaluation of the left atrium and left atrial appendage for the presence of thrombus prior to cardioversion and pulmonary vein isolation, and of the entire heart for embolic sources in the setting of cryptogenic stroke, has long been standard medical care. Guidelines have uniformly recommended transesophageal echocardiography (TEE) to accomplish these goals. In recent years, computed tomographic angiography has demonstrated diagnostic accuracy similar to that of TEE for the detection of thrombus. Analysis of the pertinent data and relative merits of the 2 technologies leads to the conclusions that: 1) both modalities have some unique, nonoverlapping capabilities that may dictate their use in specific situations; 2) computed tomographic angiography is a reasonable alternative to TEE when the primary aim is to exclude left atrial and left atrial appendage thrombus and in patients in whom the risks associated with TEE outweigh the benefits; and 3) both options should be discussed with the patient in the setting of shared decision making. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  3. Systems analysis of thrombus formation

    PubMed Central

    Diamond, Scott L.

    2016-01-01

    The systems analysis of thrombosis seeks to quantitatively predict blood function in a given vascular wall and hemodynamic context. Relevant to both venous and arterial thrombosis, a Blood Systems Biology approach should provide metrics for rate and molecular mechanisms of clot growth, thrombotic risk, pharmacological response, and utility of new therapeutic targets. As a rapidly created multicellular aggregate with a polymerized fibrin matrix, blood clots result from hundreds of unique reactions within and around platelets propagating in space and time under hemodynamic conditions. Coronary artery thrombosis is dominated by atherosclerotic plaque rupture, complex pulsatile flows through stenotic regions producing high wall shear stresses, and plaque-derived tissue factor driving thrombin production. In contrast, venous thrombosis is dominated by stasis or depressed flows, endothelial inflammation, white blood cell-derived tissue factor, and ample red blood cell incorporation. By imaging vessels, patient-specific assessment using computational fluid dynamics provides an estimate of local hemodynamics and fractional flow reserve. High dimensional ex vivo phenotyping of platelet and coagulation can now power multiscale computer simulations at the subcellular to cellular to whole vessel scale of heart attacks or strokes. Additionally, an integrated systems biology approach can rank safety and efficacy metrics of various pharmacological interventions or clinical trial designs. PMID:27126646

  4. Tanshinon IIA injection accelerates tissue expansion by reducing the formation of the fibrous capsule.

    PubMed

    Yu, Qingxiong; Sheng, Lingling; Yang, Mei; Zhu, Ming; Huang, Xiaolu; Li, Qingfeng

    2014-01-01

    The tissue expansion technique has been applied to obtain new skin tissue to repair large defects in clinical practice. The implantation of tissue expander could initiate a host response to foreign body (FBR), which leads to fibrotic encapsulation around the expander and prolongs the period of tissue expansion. Tanshinon IIA (Tan IIA) has been shown to have anti-inflammation and immunoregulation effect. The rat tissue expansion model was used in this study to observe whether Tan IIA injection systematically could inhibit the FBR to reduce fibrous capsule formation and accelerate the process of tissue expansion. Forty-eight rats were randomly divided into the Tan IIA group and control group with 24 rats in each group. The expansion was conducted twice a week to maintain a capsule pressure of 60 mmHg. The expansion volume and expanded area were measured. The expanded tissue in the two groups was harvested, and histological staining was performed; proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) and transforming growth factor-β (TGF-β) were examined. The expansion volume and the expanded area in the Tan IIA group were greater than that of the control group. The thickness of the fibrous capsule in the Tan IIA group was reduced with no influence on the normal skin regeneration. Decreased infiltration of macrophages, lower level of TNF-α, IL-6, IL-1β and TGF-β, less proliferating myofibroblasts and enhanced neovascularization were observed in the Tan IIA group. Our findings indicated that the Tan IIA injection reduced the formation of the fibrous capsule and accelerated the process of tissue expansion by inhibiting the FBR.

  5. Sonothrombolysis

    PubMed Central

    Bader, Kenneth B.; Bouchoux, Guillaume

    2016-01-01

    Thrombo-occlusive disease is a leading cause of morbidity and mortality. In this chapter, the use of ultrasound to accelerate clot breakdown alone or in combination with thrombolytic drugs will be reported. Primary thrombus formation during cardiovascular disease and standard treatment methods will be discussed. Mechanisms for ultrasound enhancement of thrombolysis, including thermal heating, radiation force, and cavitation, will be reviewed. Finally, in-vitro, in-vivo and clinical evidence of enhanced thrombolytic efficacy with ultrasound will be presented and discussed. PMID:26486347

  6. Renal cell carcinoma with thrombus extending to the hepatic veins or right atrium: operative strategies based on 41 consecutive patients.

    PubMed

    Gagné-Loranger, Maude; Lacombe, Louis; Pouliot, Frédéric; Fradet, Vincent; Dagenais, François

    2016-08-01

    The natural history of renal cell carcinoma (RCC) with tumour thrombus extending at or above the hepatic veins is dismal. Different surgical approaches have been described including cardiopulmonary bypass (CPB) with deep hypothermic circulatory arrest. We here report our experience in terms of surgical techniques and outcomes on 41 consecutive patients presenting an RCC extending to the hepatic veins or the right atrium. A surgical decision-making algorithm is discussed. Retrospective review of 41 patients operated for RCC extending in the retrohepatic vena cava (extent level III-IV) between 2000 and 2015. Patients were operated by a dedicated urology/cardiac surgery team. The mean age was 62.6 ± 10.4 years; 39% were female. Surgery was emergent in 7.3% of patients, 2.4% of patients had preoperative dialysis, 4.9% required a redo sternotomy and 19.5% had coronary artery disease. Tumour thrombus extended above the diaphragm in 23 patients (level IV) and to the level of hepatic veins (level III) in 18 patients. CPB was used in 38 patients. Arterial cannulation was in the aorta or femoral artery in 14 patients during the initial experience. In the current era, the axillary artery and the innominate artery were used in 12 patients each. Mean CPB, cross-clamp and circulatory arrest times were, respectively, 96.5 ± 42.9, 21.1 ± 16.4 and 10.2 ± 8.2 min (mean temperature of 25.7 ± 4.9°C). Hepatic exclusion without the use of CPB was performed to excise the thrombus in 3 patients. A right nephrectomy was performed in 25 patients, a left in 15 patients and a bilateral nephrectomy in 1 patient. Five patients had a partial inferior vena cava (IVC) resection, with 4 patients requiring a patch reconstruction of the IVC. Three patients had an infrarenal IVC ligation. One patient suffered a cerebrovascular accident in the postoperative period. One in-hospital death occurred (in-hospital mortality 2.4%). The mean follow-up was 1.9 ± 2.0 years. Twenty-three patients died

  7. On the Impact of Intraluminal Thrombus Mechanical Behavior in AAA Passive Mechanics.

    PubMed

    Riveros, Fabián; Martufi, Giampaolo; Gasser, T Christian; Rodriguez-Matas, Jose F

    2015-09-01

    Intraluminal thrombus (ILT) is a pseudo-tissue that develops from coagulated blood, and is found in most abdominal aortic aneurysms (AAAs) of clinically relevant size. A number of studies have suggested that ILT mechanical characteristics may be related to AAA risk of rupture, even though there is still great controversy in this regard. ILT is isotropic and inhomogeneous and may appear as a soft (single-layered) or stiff (multilayered fibrotic) tissue. This paper aims to investigate how ILT constitution and topology influence the magnitude and location of peak wall stress (PWS). In total 21 patient-specific AAAs (diameter 4.2-5.4 cm) were reconstructed from computer tomography images and biomechanically analyzed using state-of-the-art modeling assumptions. Results indicated that PWS correlated stronger with ILT volume (ρ = 0.44, p = 0.05) and minimum thickness of ILT layer (ρ = 0.73, p = 0.001) than with maximum AAA diameter (ρ = 0.05, p = 0.82). On average PWS was 20% (SD 12%) higher for FE models that used soft instead of stiff ILT models (p < 0.001). PWS location strongly correlated with sites of minimum ILT thickness in the section of maximum AAA diameter and was independent from ILT stiffness. In addition, ILT heterogeneity, i.e., the spatial composition of soft and stiff thrombus tissue, can considerably influence stress in the AAA wall. The present study is limited to identification of influential biomechanical factors, and how its findings translate to an AAA rupture risk assessment remains to be explored by clinical studies.

  8. Comparison of Acid Titration, Conductivity, Flame Photometry, ICP-MS, and Accelerated Lamellae Formation Techniques in Determining Glass Vial Quality.

    PubMed

    Fujimori, Kiyoshi; Lee, Hans; Sloey, Christopher; Ricci, Margaret S; Wen, Zai-Qing; Phillips, Joseph; Nashed-Samuel, Yasser

    2016-01-01

    Certain types of glass vials used as primary containers for liquid formulations of biopharmaceutical drug products have been observed with delamination that produced small glass like flakes termed lamellae under certain conditions during storage. The cause of this delamination is in part related to the glass surface defects, which renders the vials susceptible to flaking, and lamellae are formed during the high-temperature melting and annealing used for vial fabrication and shaping. The current European Pharmacopoeia method to assess glass vial quality utilizes acid titration of vial extract pools to determine hydrolytic resistance or alkalinity. Four alternative techniques with improved throughput, convenience, and/or comprehension were examined by subjecting seven lots of vials to analysis by all techniques. The first three new techniques of conductivity, flame photometry, and inductively coupled plasma mass spectrometry measured the same sample pools as acid titration. All three showed good correlation with alkalinity: conductivity (R(2) = 0.9951), flame photometry sodium (R(2) = 0.9895), and several elements by inductively coupled plasma mass spectrometry [(sodium (R(2) = 0.9869), boron (R(2) = 0.9796), silicon (R(2) = 0.9426), total (R(2) = 0.9639)]. The fourth technique processed the vials under conditions that promote delamination, termed accelerated lamellae formation, and then inspected those vials visually for lamellae. The visual inspection results without the lot with different processing condition correlated well with alkalinity (R(2) = 0.9474). Due to vial processing differences affecting alkalinity measurements and delamination propensity differently, the ratio of silicon and sodium measurements from inductively coupled plasma mass spectrometry was the most informative technique to assess overall vial quality and vial propensity for lamellae formation. The other techniques of conductivity, flame photometry, and accelerated lamellae formation

  9. Thrombus aspiration in non-ST-elevation myocardial infarction - 12-month clinical outcome of the randomised TATORT-NSTEMI trial.

    PubMed

    Meyer-Saraei, Roza; de Waha, Suzanne; Eitel, Ingo; Desch, Steffen; Scheller, Bruno; Böhm, Michael; Lauer, Bernward; Gawaz, Meinrad; Geisler, Tobias; Gunkel, Oliver; Bruch, Leonhard; Klein, Norbert; Pfeiffer, Dietrich; Schuler, Gerhard; Zeymer, Uwe; Thiele, Holger

    2017-02-01

    In the randomised TATORT-NSTEMI trial routine thrombus aspiration in comparison with standard percutaneous coronary intervention (PCI) did not reduce the primary endpoint of microvascular obstruction assessed by cardiac magnetic resonance imaging in patients with non-ST-elevation myocardial infarction (NSTEMI). So far, no data on long-term outcome of head-to-head comparisons between both treatment strategies in NSTEMI patients have been reported. The prospective, controlled, multicentre, randomised, open-label TATORT-NSTEMI trial assigned patients with NSTEMI and thrombus-containing lesions to aspiration thrombectomy plus PCI ( n=221) or standard PCI only ( n=219). The primary endpoint of the current analysis was the occurrence of major adverse cardiac events defined as the composite of death, myocardial reinfarction, target vessel revascularisation, and new congestive heart failure at 12-month follow-up. In addition, functional outcome and quality of life were assessed. At one year, major adverse cardiac events occurred in 19 patients in the thrombectomy arm and 29 patients in the standard PCI group (8.7% vs. 13.4%, relative risk 0.63, 95% confidence interval 0.35-1.12, p=0.11). The individual components of the combined endpoint such as death ( p=0.20), myocardial reinfarction ( p=0.73), target vessel revascularisation ( p=0.42), and congestive heart failure ( p=0.18) were similar in both groups. Functional outcome and quality of life did not differ significantly between both groups (Canadian Cardiovascular Society class: p=0.68, New York Heart Association class: p=0.70 and EuroQol5D score: p=0.96). Post-hoc analyses revealed consistent results with regard to the occurrence of major adverse cardiac events across a wide range of subgroups (all p>0.05). In this first randomised trial on thrombectomy in NSTEMI patients, routine thrombus aspiration before PCI did not improve clinical outcome at 12-month follow-up.

  10. Influence of solidification accelerators on structure formation of anhydrite-containing binders

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Anikanova, L., E-mail: alasmit@mail.ru; Volkova, O., E-mail: v.olga.nikitina@gmail.com; Kudyakov, A.

    2016-01-15

    The article presents results of scientific analysis of chemical additives influence on acid fluoride binder. It was found that the influence of sulfate nature additives on the process of hydration and solidification of the binder is similar to influence of additives on indissoluble anhydrite. Additives with SO{sub 4}{sup 2−} anion NO{sup −} are more efficient. The mentioned additives according to accelerating effect belong to the following succession: K{sub 2}SO{sub 4} > Na{sub 2}SO{sub 4} > FeSO{sub 4} > MgSO{sub 4}. Facilitation of the process of hydration and solidification of the binder, increase in density and durability of the binder (32 MPa)more » is to the greatest extent achieved with the introduction of 2% sodium sulfate additive of the binder’s mass into the composition of the binder along with the ultrasonic treatment of water solution. Directed crystal formation process with healing of porous structure by new growths presented as calcium sulfate dehydrate and hydroglauberite provides positive effect.« less

  11. Differentiation of thrombus from pannus as the cause of acquired mechanical prosthetic heart valve obstruction by non-invasive imaging: a review of the literature.

    PubMed

    Tanis, Wilco; Habets, Jesse; van den Brink, Renee B A; Symersky, Petr; Budde, Ricardo P J; Chamuleau, Steven A J

    2014-02-01

    For acquired mechanical prosthetic heart valve (PHV) obstruction and suspicion on thrombosis, recently updated European Society of Cardiology guidelines advocate the confirmation of thrombus by transthoracic echocardiography, transesophageal echocardiography (TEE), and fluoroscopy. However, no evidence-based diagnostic algorithm is available for correct thrombus detection, although this is clinically important as fibrinolysis is contraindicated in non-thrombotic obstruction (isolated pannus). Here, we performed a review of the literature in order to propose a diagnostic algorithm. We performed a systematic search in Pubmed and Embase. Included publications were assessed on methodological quality based on the validated Quality Assessment of Diagnostic Accuracy Studies (QUADAS) II checklist. Studies were scarce (n = 15) and the majority were of moderate methodological quality. In total, 238 mechanical PHV's with acquired obstruction and a reliable reference standard were included for the evaluation of the role of fluoroscopy, echocardiography, or multidetector-row computed tomography (MDCT). In acquired PHV obstruction caused by thrombosis, mass detection by TEE and leaflet restriction detected by fluoroscopy were observed in the majority of cases (96 and 100%, respectively). In contrast, in acquired PHV obstruction free of thrombosis (pannus), leaflet restriction detected by fluoroscopy was absent in some cases (17%) and mass detection by TEE was absent in the majority of cases (66%). In case of mass detection by TEE, predictors for obstructive thrombus masses (compared with pannus masses) were leaflet restriction, soft echo density, and increased mass length. In situations of inconclusive echocardiography, MDCT may correctly detect pannus/thrombus based on the morphological aspects and localization. In acquired mechanical PHV obstruction without leaflet restriction and absent mass on TEE, obstructive PHV thrombosis cannot be confirmed and consequently, fibrinolysis

  12. Early thrombus removal strategies for acute deep venous thrombosis: clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum.

    PubMed

    Meissner, Mark H; Gloviczki, Peter; Comerota, Anthony J; Dalsing, Michael C; Eklof, Bo G; Gillespie, David L; Lohr, Joann M; McLafferty, Robert B; Murad, M Hassan; Padberg, Frank; Pappas, Peter; Raffetto, Joseph D; Wakefield, Thomas W

    2012-05-01

    The anticoagulant treatment of acute deep venous thrombosis (DVT) has been historically directed toward the prevention of recurrent venous thromboembolism. However, such treatment imperfectly protects against late manifestations of the postthrombotic syndrome. By restoring venous patency and preserving valvular function, early thrombus removal strategies can potentially decrease postthrombotic morbidity. A committee of experts in venous disease was charged by the Society for Vascular Surgery and the American Venous Forum to develop evidence-based practice guidelines for early thrombus removal strategies, including catheter-directed pharmacologic thrombolysis, pharmacomechanical thrombolysis, and surgical thrombectomy. Evidence-based recommendations are based on a systematic review and meta-analysis of the relevant literature, supplemented when necessary by less rigorous data. Recommendations are made according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, incorporating the strength of the recommendation (strong: 1; weak: 2) and an evaluation of the level of the evidence (A to C). On the basis of the best evidence currently available, we recommend against routine use of the term "proximal venous thrombosis" in favor of more precise characterization of thrombi as involving the iliofemoral or femoropopliteal venous segments (Grade 1A). We further suggest the use of early thrombus removal strategies in ambulatory patients with good functional capacity and a first episode of iliofemoral DVT of <14 days in duration (Grade 2C) and strongly recommend their use in patients with limb-threatening ischemia due to iliofemoral venous outflow obstruction (Grade 1A). We suggest pharmacomechanical strategies over catheter-directed pharmacologic thrombolysis alone if resources are available and that surgical thrombectomy be considered if thrombolytic therapy is contraindicated (Grade 2C). Most data regarding early thrombus removal

  13. Rivaroxaban as an effective alternative to warfarin in a patient with atrial fibrillation, thrombophilia, and left atrial appendage thrombus: a case report.

    PubMed

    Scarano, Michele; Casale, Matteo; Mantini, Cesare; Imbalzano, Egidio; Consorti, Cristiana; Clemente, Daniela; Dattilo, Giuseppe

    2017-04-09

    Atrial fibrillation is the most common cardiac arrhythmia. It is responsible for up to 20% of all ischemic strokes. Rate control and anticoagulation are crucial for atrial fibrillation management and stroke prevention. We present the case of an 84-year-old Italian woman with a left atrial appendage thrombus that developed despite her use of anticoagulant therapy with warfarin for a previous pulmonary embolism. She had atrial fibrillation and heterozygosity for both factor V Leiden and methylenetetrahydrofolate reductase C677T mutation, thus creating resistance to activated protein C. Anticoagulant therapy was switched to heparin for 1 week and then to rivaroxaban. After 3 months of rivaroxaban use, the thrombus disappeared. This case raises the issue of the ineffectiveness of warfarin therapy in complex cases involving particular thrombophilic conditions and the possibility of using rivaroxaban as a safe and effective alternative.

  14. Compact Torus Acceleration and Injection Experiment

    NASA Astrophysics Data System (ADS)

    Fukumoto, Naoyuki; Fujiwara, Makoto; Nagata, Masayoshi; Uyama, Tadao; Oda, Yasushi; Azuma, Kingo

    1996-11-01

    The spheromak-type compact torus (CT) acceleration and injection experiment has been carried out using the Himeji Institute of Technology Compact Torus Injector (HIT-CTI). We explore the possibility of refueling, density control, current drive, and edge electric field control of tokamak plasma by means of CT injection. In last September the new HIT-CTI was built up to achieve higher speed (Vct>200 km/s) and higher density CT plasmoid by improving the capacitor bank system and eliminating the impurity and neutral particles. At initial formation discharge tests the gun for formation and compression successfully produced a CT plasmoid and injected it between electrodes for acceleration. (Initial velocity Vct.ini. 32 km/s, Bct 1 kG, Rct=5.5 cm). The formation capacitor bank will be upgraded to two 36 mF capacitors operating at 20 kV (14.4 kJ). The acceleration capacitor bank will be also upgraded to two 36 mF capacitors operating at 20 kV (14.4 kJ). The HIT-CTI will be optimized to obtain suitable CT parameters after acceleration (Bct>5 kG, Lct 20 cm, Vct>200 km/s). In the respect of CT parameter measurement magnetic probes and a He-Ne laser interferometer will be employed in order to measure the CT magnetic field, velocity, density, and length. CT acceleration experimental data on the HIT-CTI and the plan of CT injection experiment on the JFT-2M tokamak (JAERI) will be presented at the meeting.

  15. Pulse infusion thrombolysis (PIT) for large intracoronary thrombus: preventive effect against the 'no flow' phenomenon in revascularization therapy for acute myocardial infarction.

    PubMed

    Saito, T; Hokimoto, S; Ishibashi, F; Noda, K; Oshima, S

    2001-02-01

    Because large thrombus is a limitation for revascularization in acute myocardial infarction (AMI), the present study evaluated the effectiveness of pulse infusion thrombolysis (PIT) in patients with an AMI with a large (>15 mm) coronary thrombus, focusing on the occurrence of the 'no flow' phenomenon. The retrospective study compared patients treated before (1988-95; Group A, n=74) and after (1996-99; Group B, n=40) the use of PIT, using the following parameters: lesion success (<50% stenosis during 30-min observation), procedural success (lesion success plus TIMI grade 3 flow), procedural no flow (TIMI grade 0 flow during the procedure with 'back and forth movement' of contrast dye after lesion success), persistent no flow (consistent no flow without any flow improvement at the final visualization despite intensive treatment), reocclusion rate and in-hospital death. Group B was significantly better than Group A in procedural success (90% vs 66%; p=0.005), procedural 'no flow' (51% vs 15%; p<0.001), and persistent 'no flow' (34% vs 10%; p<0.05). Subgroup comparison was performed among the following groups: Direct-BA group (n=44): treated with mechanical angioplasty alone; ICT-BA group (n=40): treated with prior intracoronary thrombolysis and angioplasty; and PIT-BA group (n=30): treated with PIT and angioplasty. There were no differences in thrombus length and lesion success among these 3 groups. Procedural success was best achieved in PIT-BA: 97% vs 52% for Direct-BA (p=0.003) and 68% for ICT-BA (p=0.009). Procedural 'no flow' was least in PIT-BA: 50% vs 3.3% for Direct-BA (p=0.003) and 25% vs 3.3% for ICT-BA (p=0.042). Persistent 'no flow' was less frequent in PIT-BA than Direct-BA: 32% vs 3.3% (p=0.009). However, the difference between ICT-BA and Direct-BA was insignificant: 13% vs 3.3% (p=0.53). There were no differences in reocclusion rate and in-hospital death among the 3 subgroups. And there were no differences between Direct-BA and ICT-BA in any parameters

  16. Thrombus Extraction Catheters vs. Angiojet Rheolytic Thrombectomy in Thrombotic Lesions/SV Grafts

    PubMed Central

    Alexopoulos, Dimitrios; Davlouros, Periklis A

    2012-01-01

    Primary percutaneous coronary intervention, (pPCI), of native coronaries and saphenous vein grafts (SVGs), is the recommended reperfusion strategy for STEMI, and an early invasive approach is recommended for high risk patients with UA/NSTEMI. Although PCI effectively restores flow in the infarct related artery/culprit vessel in both situations, myocardial perfusion often remains suboptimal due to microvascular obstruction, partly attributed to distal embolization of thrombus. Hence, thrombectomy (manual or mechanical), prior to stenting may further reduce hard clinical end points in patients with ACS. This article discusses accumulated evidence regarding the safety and effectiveness of thrombectomy in culprit native coronaries and SVGs in such patients, as well as possible strategies for maximizing its benefits relative to the size of the thrombotic burden. PMID:22920486

  17. Carbon nanotubes functionalized with fibroblast growth factor accelerate proliferation of bone marrow-derived stromal cells and bone formation

    NASA Astrophysics Data System (ADS)

    Hirata, Eri; Ménard-Moyon, Cécilia; Venturelli, Enrica; Takita, Hiroko; Watari, Fumio; Bianco, Alberto; Yokoyama, Atsuro

    2013-11-01

    Multi-walled carbon nanotubes (MWCNTs) were functionalized with fibroblast growth factor (FGF) and the advantages of their use as scaffolds for bone augmentation were evaluated in vitro and in vivo. The activity of FGF was assessed by measuring the effect on the proliferation of rat bone marrow stromal cells (RBMSCs). The presence of FGF enhanced the proliferation of RBMSCs and the FGF covalently conjugated to the nanotubes (FGF-CNT) showed the same effect as FGF alone. In addition, FGF-CNT coated sponges were implanted between the parietal bone and the periosteum of rats and the formation of new bone was investigated. At day 14 after implantation, a larger amount of newly formed bone was clearly observed in most pores of FGF-CNT coated sponges. These findings indicated that MWCNTs accelerated new bone formation in response to FGF, as well as the integration of particles into new bone during its formation. Scaffolds coated with FGF-CNT could be considered as promising novel substituting materials for bone regeneration in future tissue engineering applications.

  18. Managing iliofemoral deep venous thrombosis of pregnancy with a strategy of thrombus removal is safe and avoids post-thrombotic morbidity.

    PubMed

    Herrera, Santiago; Comerota, Anthony J; Thakur, Subhash; Sunderji, Shiraz; DiSalle, Robert; Kazanjian, Sahira N; Assi, Zakaria

    2014-02-01

    Extensive deep venous thrombosis (DVT) during pregnancy is usually treated with anticoagulation alone, risking significant post-thrombotic syndrome (PTS) in young patients. Catheter-directed thrombolysis (CDT) and operative venous thrombectomy have been safely and effectively used in nonpregnant patients, demonstrating significant reduction in post-thrombotic morbidity. This report reviews short- and long-term outcomes of 13 patients with extensive DVT of pregnancy treated with a strategy of thrombus removal. From 1999 to 2013, 13 patients with iliofemoral DVT during pregnancy were offered CDT, pharmacomechanical thrombolysis (PMT), and/or venous thrombectomy. Gestational age ranged from 8 to 34 weeks. Fetal monitoring was performed throughout hospitalization. Radiation exposure was minimized with pelvic lead shields, focal fluoroscopy, and limited angiographic runs. Follow-up included objective vein evaluation using venous duplex and PTS assessment using the Villalta scale. CDT and/or PMT were used in 11 patients. Two patients underwent venous thrombectomy alone, and one patient had operative thrombectomy as an adjunct to CDT and PMT. Each patient had complete or near-complete thrombus resolution and rapid improvement in clinical symptoms. Eight of 11 having CDT or PMT underwent venoplasty and stenting of the involved iliac veins. Twelve of the 13 delivered healthy infants at term. One patient opted for termination of her pregnancy. Mean patient and gestational ages were 26 years and 26 weeks, respectively. Mean follow-up was 1.3 years, with only one recurrence. Duplex ultrasonography demonstrated patent veins in all but one patient and normal valve function in 10 patients. Eleven patients had Villalta scores <5 (considered normal), with a mean score of 0.7. Extensive DVT of pregnancy can be effectively and safely treated with a strategy of thrombus removal, resulting in a patent venous system, normal valve function in many, prevention of PTS, and reduction in

  19. Combined MR direct thrombus imaging and non-contrast magnetic resonance venography reveal the evolution of deep vein thrombosis: a feasibility study.

    PubMed

    Mendichovszky, I A; Priest, A N; Bowden, D J; Hunter, S; Joubert, I; Hilborne, S; Graves, M J; Baglin, T; Lomas, D J

    2017-06-01

    Lower limb deep venous thrombosis (DVT) is a common condition with high morbidity and mortality. The aim of the study was to investigate the temporal evolution of the acute thrombus by magnetic resonance imaging (MRI) and its relationship to venous recanalization in patients with recurrent DVTs. Thirteen patients with newly diagnosed lower limb DVTs underwent MRI with non-contrast MR venography (NC-MRV) and MR direct thrombus imaging (MR-DTI), an inversion-recovery water-selective fast gradient-echo acquisition. Imaging was performed within 7 days of the acute thrombotic event, then at 3 and 6 months. By 3 months from the thrombotic event a third of the thrombi had resolved and by 6 months about half of the cases had resolved on the basis of vein recanalisation using NC-MRV. On the initial MR-DTI acute thrombus was clearly depicted by hyperintense signal, while the remaining thrombi were predominantly low signal at 3 and 6 months. Some residual thrombi contained small and fragmented persisting hyperintense areas at 3 months, clearing almost completely by 6 months. Our study suggests that synergistic venous assessment with combined NC-MRV and MR-DTI is able to distinguish acute venous thrombosis from the established (old) or evolving DVT detected by ultrasound. • MRI can distinguish between acute and evolving or chronic lower limb DVT • Two advanced MRI techniques can follow the evolution of lower limb DVT • MRI could be used to avoid an incorrect diagnosis of recurrent DVT • MRI could help avoid the risks and complications of lifelong anticoagulation therapy.

  20. Intervention radiology for venous thrombosis: early thrombus removal using invasive methods.

    PubMed

    Casanegra, Ana I; McBane, Robert D; Bjarnason, Haraldur

    2017-04-01

    The post thrombotic syndrome is one of the most dreaded complications of proximal deep vein thrombosis. This syndrome leads to pain and suffering with leg swelling, recalcitrant ulceration and venous claudication which greatly impairs mobility and quality of life. The prevalence can be high in patients with iliofemoral venous involvement particularly in the setting of a proximal venous stenosis, such as occurs in May Thurner syndrome. Anticoagulation alone does not reduce the likelihood of this outcome. Compression therapy may be effective but garment discomfort limits its implementation. Pharmacomechanical thrombectomy, which combines catheter-directed thrombolysis with mechanical thrombus dissolution, provides an attractive treatment strategy for such patients. The rationale and delivery of pharmacomechanical thrombectomy, including patient selection and adjunctive antithrombotic therapy, will be reviewed in addition to tips and tricks for managing difficult patient scenarios. © 2017 John Wiley & Sons Ltd.

  1. The Abdominal Aortic Aneurysm and Intraluminal Thrombus: Current Concepts of Development and Treatment

    PubMed Central

    Piechota-Polanczyk, Aleksandra; Jozkowicz, Alicja; Nowak, Witold; Eilenberg, Wolf; Neumayer, Christoph; Malinski, Tadeusz; Huk, Ihor; Brostjan, Christine

    2015-01-01

    The pathogenesis of the abdominal aortic aneurysm (AAA) shows several hallmarks of atherosclerotic and atherothrombotic disease, but comprises an additional, predominant feature of proteolysis resulting in the degradation and destabilization of the aortic wall. This review aims to summarize the current knowledge on AAA development, involving the accumulation of neutrophils in the intraluminal thrombus and their central role in creating an oxidative and proteolytic environment. Particular focus is placed on the controversial role of heme oxygenase 1/carbon monoxide and nitric oxide synthase/peroxynitrite, which may exert both protective and damaging effects in the development of the aneurysm. Treatment indications as well as surgical and pharmacological options for AAA therapy are discussed in light of recent reports. PMID:26664891

  2. Accelerated anaerobic release of K, Mg and P from surplus activated sludge for element recovery and struvite formation inhibition.

    PubMed

    Ito, A; Kawakami, H; Ishikawa, N; Ito, M; Oikawa, T; Sato, A; Umita, T

    2017-05-01

    Accelerated release of potassium (K), magnesium (Mg) and phosphorus (P) from surplus activated sludge (SAS) was investigated to develop a new system for the recovery of the elements. Anaerobic cultivation of SAS during 24 h released 78% of K and about 50% of Mg and P from SAS more effectively compared to aerobic cultivation (K: 40%, Mg: 15%, P: 15%). Furthermore, the addition of sodium acetate as an organic carbon source remarkably accelerated the release of K, Mg and P from SAS under anaerobic condition. However, no increase in the maximum release efficiencies was observed. The elements released from SAS could be transferred to separate liquid with the existing mechanical thickener and be recovered as MgKPO 4 by some additional process. Furthermore, the removal of the elements from SAS would inhibit the formation of struvite causing the blockage of sludge transport pipe after anaerobic digestion process of thickened sludge.

  3. Accelerated and enhanced bone formation on novel simvastatin-loaded porous titanium oxide surfaces.

    PubMed

    Nyan, Myat; Hao, Jia; Miyahara, Takayuki; Noritake, Kanako; Rodriguez, Reena; Kasugai, Shohei

    2014-10-01

    With increasing application of dental implants in poor-quality bones, the need for implant surfaces ensuring accelerated osseointegration and enhanced peri-implant bone regeneration is increased. A study was performed to evaluate the osseointegration and bone formation on novel simvastatin-loaded porous titanium oxide surface. Titanium screws were treated by micro-arc oxidation to form porous oxide surface and 25 or 50 μg of simvastatin was loaded. The nontreated control, micro-arc oxidized, and simvastatin-loaded titanium screws were surgically implanted into the proximal tibia of 16-week-old male Wistar rats (n = 36). Peri-implant bone volume, bone-implant contact, and mineral apposition rates were measured at 2 and 4 weeks. Data were analyzed by one-way analysis of variance followed by Tukey's post hoc test. New bone was formed directly on the implant surface in the bone marrow cavity in simvastatin-loaded groups since 2 weeks. Bone-implant contact values were significantly higher in simvastatin-loaded groups than control and micro-arc oxidized groups at both time points (p < .05). Peri-implant bone volume and mineral apposition rate of simvastatin-loaded groups were significantly higher than control and micro-arc oxidized groups at 2 weeks (p < .05). These data suggested that simvastatin-loaded porous titanium oxide surface provides faster osseointegration and peri-implant bone formation and it would be potentially applicable in poor-quality bones. © 2013 Wiley Periodicals, Inc.

  4. Enhancing Tumor Drug Delivery by Laser-Activated Vascular Barrier Disruption

    DTIC Science & Technology

    2009-12-01

    found platelet aggregation, thrombus formation and endothelial cell rupture (Fig 1). All these findings demonstrate that PDT damages endothelial...after 0.5 mg/kg verteporfin (i.v.)). (A) 1 h after PDT showing platelet aggregation and thrombus formation; (B) 6 h after PDT showing edema...mechanisms causing thrombi formation. Other mechanisms, such as release of thromboxane from platelets (33) and von Willebrand factor from damaged

  5. The effect of interstitial air on the in vitro thrombogenicity of ePTFE vascular grafts

    NASA Technical Reports Server (NTRS)

    Rashid, S. N.; Clark, H. G.; Vann, R. D.; Gerth, W. A.; Palmos, L. A.; Mikat, E. M.

    1992-01-01

    Gas trapped in the interstices of the biomaterials used for vascular prostheses causes thrombosis, and the process of eliminating this gas is known as denucleation. An apparatus was developed for testing in the in vitro effects of denucleation on 4 mm I.D. expanded polytetrafluoroethylene (ePTFE) Vitagraft (Johnson and Johnson). The apparatus was designed to ensure that neither the blood nor the grafts came in contact with air. Blood from a single donor was incubated with control and denucleated grafts for 5, 10, 15, 20, and 30 minutes. The thrombus volume in the graft lumen was measured with a computer assisted videometric system. Little thrombus formed by 5 or 10 minutes, but there was less thrombus in the denucleated graft than in the control graft at all times. The differences were statistically significant at 15 and 20 minutes (p < 0.05). Denucleation nearly doubled the thrombus formation time. Thrombus was more adherent to denucleated grafts than to control grafts. These results are consistent with in vivo observations in the rat where denucleation decreased thrombus formation and increased patency duration.

  6. Diagnosing upper extremity deep vein thrombosis with non-contrast-enhanced Magnetic Resonance Direct Thrombus Imaging: A pilot study.

    PubMed

    Dronkers, C E A; Klok, F A; van Haren, G R; Gleditsch, J; Westerlund, E; Huisman, M V; Kroft, L J M

    2018-03-01

    Diagnosing upper extremity deep vein thrombosis (UEDVT) can be challenging. Compression ultrasonography is often inconclusive because of overlying anatomic structures that hamper compressing veins. Contrast venography is invasive and has a risk of contrast allergy. Magnetic Resonance Direct Thrombus Imaging (MRDTI) and Three Dimensional Turbo Spin-echo Spectral Attenuated Inversion Recovery (3D TSE-SPAIR) are both non-contrast-enhanced Magnetic Resonance Imaging (MRI) sequences that can visualize a thrombus directly by the visualization of methemoglobin, which is formed in a fresh blood clot. MRDTI has been proven to be accurate in diagnosing deep venous thrombosis (DVT) of the leg. The primary aim of this pilot study was to test the feasibility of diagnosing UEDVT with these MRI techniques. MRDTI and 3D TSE-SPAIR were performed in 3 pilot patients who were already diagnosed with UEDVT by ultrasonography or contrast venography. In all patients, UEDVT diagnosis could be confirmed by MRDTI and 3D TSE-SPAIR in all vein segments. In conclusion, this study showed that non-contrast MRDTI and 3D TSE-SPAIR sequences may be feasible tests to diagnose UEDVT. However diagnostic accuracy and management studies have to be performed before these techniques can be routinely used in clinical practice. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Laser-Activated Shape Memory Polymer Microactuator for Thrombus Removal Following Ischemic Stroke: Preliminary In Vitro Analysis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Small, W; Metzger, M F; Wilson, T S

    2004-09-23

    Due to the narrow (3-hour) treatment window for effective use of the thrombolytic drug recombinant tissue-type plasminogen activator (rt-PA), there is a need to develop alternative treatments for ischemic stroke. We are developing an intravascular device for mechanical thrombus removal using shape memory polymer (SMP). We propose to deliver the SMP microactuator in its secondary straight rod form (length = 4 cm, diameter = 350 {micro}m) through a catheter distal to the vascular occlusion. The microactuator, which is mounted on the end of an optical fiber, is then transformed into its primary corkscrew shape by laser heating (diode laser, {lambda}more » = 800 nm) above its soft phase glass transition temperature (T{sub gs} = 55 C). Once deployed, the microactuator is retracted and the captured thrombus is removed to restore blood flow. The SMP is doped with indocyanine green (ICG) dye to increase absorption of the laser light. Successful deployment of the microactuator depends on the optical properties of the ICG-doped SMP and the optical coupling efficiency of the interface between the optical fiber and the SMP. Spectrophotometry, thermal imaging, and computer simulation aided the initial design effort and continue to be useful tools for optimization of the dye concentration and laser power. Thermomechanical testing was performed to characterize the elastic modulus of the SMP. We have demonstrated laser-activation of the SMP microactuator in air at room temperature, suggesting this concept is a promising therapeutic alternative to rt-PA.« less

  8. Monitoring of coagulation factor therapy in patients with von Willebrand disease type 3 using a microchip flow chamber system.

    PubMed

    Ågren, Anna; Holmström, Margareta; Schmidt, David E; Hosokawa, Kazuya; Blombäck, Margareta; Hjemdahl, Paul

    2017-01-05

    Patients with type 3 von Willebrand disease (VWD-3) have no measurable levels of VW factor (VWF) and usually require treatment with VWF-FVIII concentrate to prevent and/or stop bleeding. Even though the patients are treated prophylactically, they may experience bleeding symptoms. The aim of this study was to evaluate the effect of VWF-FVIII concentrate treatment in VWD-3 patients with the Total Thrombus Analysis System (T-TAS ® ), which measures thrombus formation under flow conditions. Coagulation profiles of 10 VWD-3 patients were analysed using T-TAS before and 30 minutes after VWF-FVIII concentrate (Haemate ® ) injection. Results were compared to VWF- and FVIII activity in plasma, and results with thromboelastometry and ristocetin-activated platelet impedance aggregometry (Multiplate ® ) in whole blood. For comparison, 10 healthy controls were also analysed with T-TAS. A median dose of 27 (range 15-35) IU/kg of VWF-FVIII concentrate increased VWF- and FVIII activity as expected. T-TAS thrombus formation was enhanced when a tissue factor/collagen-coated flow chamber was used at low shear, but treatment effects at high shear using a collagen-coated flow chamber were minimal. Whole blood coagulation assessed by thromboelastometry was normal and did not change (p > 0.05) but ristocetin-induced platelet aggregation improved (p < 0.001). In conclusion, T-TAS detects effects of VWF-FVIII concentrate treatment on coagulation-dependent thrombus formation at low shear, but minor effects are observed on platelet-dependent thrombus formation at high shear. The poor prediction of bleeding by conventional laboratory monitoring in VWD-3 patients might be related to insufficient restoration of platelet-dependent thrombus formation.

  9. Immunohistological Analysis of Intracoronary Thrombus Aspirate in STEMI Patients: Clinical Implications of Pathological Findings.

    PubMed

    Blasco, Ana; Bellas, Carmen; Goicolea, Leyre; Muñiz, Ana; Abraira, Víctor; Royuela, Ana; Mingo, Susana; Oteo, Juan Francisco; García-Touchard, Arturo; Goicolea, Francisco Javier

    2017-03-01

    Thrombus aspiration allows analysis of intracoronary material in patients with ST-segment elevation myocardial infarction. Our objective was to characterize this material by immunohistology and to study its possible association with patient progress. This study analyzed a prospective cohort of 142 patients undergoing primary angioplasty with positive coronary aspiration. Histological examination of aspirated samples included immunohistochemistry stains for the detection of plaque fragments. The statistical analysis comprised histological variables (thrombus age, degree of inflammation, presence of plaque), the patients' clinical and angiographic features, estimation of survival curves, and logistic regression analysis. Among the histological markers, only the presence of plaque (63% of samples) was associated with postinfarction clinical events. Factors associated with 5-year event-free survival were the presence of plaque in the aspirate (82.2% vs 66.0%; P = .033), smoking (82.5% smokers vs 66.7% nonsmokers; P = .036), culprit coronary artery (83.3% circumflex or right coronary artery vs 68.5% anterior descending artery; P = .042), final angiographic flow (80.8% II-III vs 30.0% 0-I; P < .001) and left ventricular ejection fraction ≥ 35% at discharge (83.7% vs 26.7%; P < .001). On multivariable Cox regression analysis with these variables, independent predictors of event-free survival were the presence of plaque (hazard ratio, 0.37; 95%CI, 0.18-0.77; P = .008), and left ventricular ejection fraction (hazard ratio, 0.92; 95%CI, 0.88-0.95; P < .001). The presence of plaque in the coronary aspirate of patients with ST elevation myocardial infarction may be an independent prognostic marker. CD68 immunohistochemical stain is a good method for plaque detection. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  10. Intraluminal cell transplantation prevents growth and rupture in a model of rupture-prone saccular aneurysms.

    PubMed

    Marbacher, Serge; Frösén, Juhana; Marjamaa, Johan; Anisimov, Andrey; Honkanen, Petri; von Gunten, Michael; Abo-Ramadan, Usama; Hernesniemi, Juha; Niemelä, Mika

    2014-12-01

    Aneurysm occlusion by intraluminal thrombus formation is the desired effect of all endovascular treatments. Intraluminal thrombus may, however, recanalize and be absorbed, unless it is infiltrated by cells that turn it into fibrous tissue (neointima). Because ruptured aneurysm walls are characterized by loss of smooth muscle cells, we assessed the impact of mural cell loss on wall remodeling of thrombosed aneurysms and investigated whether neointima formation could be enhanced by direct transplantation of cells into the thrombus. Sidewall aneurysms were microsurgically created in rats (n=81). Certain aneurysms were decellularized. Thrombosis was induced using direct injection of a fibrin polymer into the aneurysm. CM-Dil-labeled smooth muscle cells were injected into 25 of 46 fibrin embolized aneurysms. Recanalization and aneurysm growth were monitored with magnetic resonance angiography. Endoscopy, optical projection tomography, histology, and immunohistochemistry were used to study the fate of transplanted cells, thrombus organization, and neointima formation. Decellularized embolized aneurysms demonstrated higher angiographic recurrence compared with decellularized embolized aneurysms with transplanted cells (P=0.037). Local cell replacement at the time of thrombosis resulted in better histological neointima formation than both nondecellularized embolized aneurysms (P<0.001) and decellularized embolized aneurysms (P=0.002). Aneurysm growth and rupture were observed exclusively in decellularized embolized aneurysms. Lack of smooth muscle cells in the aneurysm wall promotes wall degradation, aneurysm growth and rupture, even if the aneurysm is occluded by luminal thrombus. Transplantation of smooth muscle cells into the luminal thrombus can reduce this degenerative remodeling. © 2014 American Heart Association, Inc.

  11. Zero, minimum and maximum relative radial acceleration for planar formation flight dynamics near triangular libration points in the Earth-Moon system

    NASA Astrophysics Data System (ADS)

    Salazar, F. J. T.; Masdemont, J. J.; Gómez, G.; Macau, E. E.; Winter, O. C.

    2014-11-01

    Assume a constellation of satellites is flying near a given nominal trajectory around L4 or L5 in the Earth-Moon system in such a way that there is some freedom in the selection of the geometry of the constellation. We are interested in avoiding large variations of the mutual distances between spacecraft. In this case, the existence of regions of zero and minimum relative radial acceleration with respect to the nominal trajectory will prevent from the expansion or contraction of the constellation. In the other case, the existence of regions of maximum relative radial acceleration with respect to the nominal trajectory will produce a larger expansion and contraction of the constellation. The goal of this paper is to study these regions in the scenario of the Circular Restricted Three Body Problem by means of a linearization of the equations of motion relative to the periodic orbits around L4 or L5. This study corresponds to a preliminar planar formation flight dynamics about triangular libration points in the Earth-Moon system. Additionally, the cost estimate to maintain the constellation in the regions of zero and minimum relative radial acceleration or keeping a rigid configuration is computed with the use of the residual acceleration concept. At the end, the results are compared with the dynamical behavior of the deviation of the constellation from a periodic orbit.

  12. Nicotine drives neutrophil extracellular traps formation and accelerates collagen-induced arthritis.

    PubMed

    Lee, Jaejoon; Luria, Ayala; Rhodes, Christopher; Raghu, Harini; Lingampalli, Nithya; Sharpe, Orr; Rada, Balazs; Sohn, Dong Hyun; Robinson, William H; Sokolove, Jeremy

    2017-04-01

    The aim was to investigate the effects of nicotine on neutrophil extracellular traps (NETs) formation in current and non-smokers and on a murine model of RA. We compared spontaneous and phorbol 12-myristate 13-acetate-induced NETosis between current and non-smokers by DNA release binding. Nicotine-induced NETosis from non-smokers was assessed by DNA release binding, NET-specific (myeloperoxidase (MPO)-DNA complex) ELISA and real-time fluorescence microscopy. We also used immunofluorescent staining to detect nicotinic acetylcholine receptors (nAChRs) on neutrophils and performed a functional analysis to assess the role of nAChRs in nicotine-induced NETosis. Finally, we investigated the effects of systemic nicotine exposure on arthritis severity and NETosis in the CIA mouse model. Neutrophils derived from current smokers displayed elevated levels of spontaneous and phorbol 12-myristate 13-acetate-induced NETosis. Nicotine induced dose-dependent NETosis in ex vivo neutrophils from healthy non-smokers, and co-incubation with ACPA-immune complexes or TNF-α facilitated a synergistic effect on NETosis. Real-time fluorescence microscopy revealed robust formation of NET-like structures in nicotine-exposed neutrophils. Immunofluorescent staining demonstrated the presence of the α7 subunit of the nAChR on neutrophils. Stimulation of neutrophils with an α7-specific nAChR agonist induced NETosis, whereas pretreatment with an nAChR antagonist attenuated nicotine-induced NETosis. Nicotine administration to mice with CIA exacerbated inflammatory arthritis, with higher plasma levels of NET-associated MPO-DNA complex. We demonstrate that nicotine is a potent inducer of NETosis, which may play an important role in accelerating arthritis in the CIA model. This study generates awareness of and the mechanisms by which nicotine-containing products, including e-cigarettes, may have deleterious effects on patients with RA. Published by Oxford University Press 2016. This work is written

  13. Use of multidetector-row computed tomography scan to detect pannus formation in prosthetic mechanical aortic valves.

    PubMed

    Aladmawi, Mohamed A; Pragliola, Claudio; Vriz, Olga; Galzerano, Domenico

    2017-04-01

    Obstruction of a mechanical aortic valve by pannus formation at the subvalvular level is a major long-term complication of aortic valve replacement (AVR). In fact, pannus is sometime difficult to differentiate from patient-prosthesis mismatch or valve thrombosis. In most cases cine-angiography and echocardiography, either transthoracic or transesophageal, cannot correctly visualize the complication when the leaflets show a normal mobility. Recent technological refinements made this difficult diagnosis possible by ECG-gated computed tomography (CT) scan which shows adequate images in 90% of the cases and can differentiate pannus from fresh and organized thrombus.

  14. The Los Alamos Laser Acceleration of Particles Workshop and beginning of the advanced accelerator concepts field

    NASA Astrophysics Data System (ADS)

    Joshi, C.

    2012-12-01

    The first Advanced Acceleration of Particles-AAC-Workshop (actually named Laser Acceleration of Particles Workshop) was held at Los Alamos in January 1982. The workshop lasted a week and divided all the acceleration techniques into four categories: near field, far field, media, and vacuum. Basic theorems of particle acceleration were postulated (later proven) and specific experiments based on the four categories were formulated. This landmark workshop led to the formation of the advanced accelerator R&D program in the HEP office of the DOE that supports advanced accelerator research to this day. Two major new user facilities at Argonne and Brookhaven and several more directed experimental efforts were built to explore the advanced particle acceleration schemes. It is not an exaggeration to say that the intellectual breadth and excitement provided by the many groups who entered this new field provided the needed vitality to then recently formed APS Division of Beams and the new online journal Physical Review Special Topics-Accelerators and Beams. On this 30th anniversary of the AAC Workshops, it is worthwhile to look back at the legacy of the first Workshop at Los Alamos and the fine groundwork it laid for the field of advanced accelerator concepts that continues to flourish to this day.

  15. Increase in the Acceleration Efficiency of Solids in a Hybrid Coaxial Magnetoplasma Accelerator

    NASA Astrophysics Data System (ADS)

    Gerasimov, D. Yu.; Sivkov, A. A.

    2018-01-01

    It is shown that in a hybrid coaxial magnetoplasma accelerator with a channel length of 350 mm and a diameter of 23 mm, the acceleration velocity and the energy conversion efficiency increase as the length of the plasma structure formation channel filled with a gas-generating material decreases from 17 to 9 mm. It is found that it is reasonable to use paraffin as the gas-generating material as it has a less significant deionizing effect on the high-current arc discharge and hence causes a less significant decrease in the discharge current intensity and an increase in conductive and inductive electrodynamic forces.

  16. Quantitative photoacoustic characterization of blood clot in blood: A mechanobiological assessment through spectral information

    NASA Astrophysics Data System (ADS)

    Biswas, Deblina; Vasudevan, Srivathsan; Chen, George C. K.; Sharma, Norman

    2017-02-01

    Formation of blood clots, called thrombus, can happen due to hyper-coagulation of blood. Thrombi, while moving through blood vessels can impede blood flow, an important criterion for many critical diseases like deep vein thrombosis and heart attacks. Understanding mechanical properties of clot formation is vital for assessment of severity of thrombosis and proper treatment. However, biomechanics of thrombus is less known to clinicians and not very well investigated. Photoacoustic (PA) spectral response, a non-invasive technique, is proposed to investigate the mechanism of formation of blood clots through elasticity and also differentiate clots from blood. Distinct shift (increase in frequency) of the PA response dominant frequency during clot formation is reported. In addition, quantitative differentiation of blood clots from blood has been achieved through parameters like dominant frequency and spectral energy of PA spectral response. Nearly twofold increases in dominant frequency in blood clots compared to blood were found in the PA spectral response. Significant changes in energy also help in quantitatively differentiating clots from blood, in the blood. Our results reveal that increase in density during clot formation is reflected in the PA spectral response, a significant step towards understanding the mechanobiology of thrombus formation. Hence, the proposed tool, in addition to detecting thrombus formation, could reveal mechanical properties of the sample through quantitative photoacoustic spectral parameters.

  17. Thrombus resolution and right ventricular functional recovery using ultrasound-accelerated thrombolysis in acute massive and submassive pulmonary embolism.

    PubMed

    Ozcinar, Evren; Cakici, Mehmet; Dikmen Yaman, Nur; Baran, Cagdas; Aliyev, Anar; Inan, Bahadir; Durdu, Serkan; Akar, Ahmet R; Sirlak, Mustafa

    2017-10-01

    This study aims to evaluate the efficacy and safety of ultrasound-accelerated catheter-directed thrombolysis (UACDT) in the treatment of massive and submassive pulmonary embolism (PE). We conducted a prospective, observational cohort study of consequtive patients with massive or submassive PE treated with low-dose UACDT using EKOS EkoSonic® system at single center from May 2014 until April 2015. Overall, thirty-eight patients (median age, 64.5 years) were included. The primary safety outcomes were change in right ventricular (RV) to left ventricular (LV) diameter ratio within 24 hours of procedure initiation, at 1- and 6-month follow-up and major bleeding within 96 hours of the procedure initiation. BNP, troponin and D-dimer levels were also measured. The ultrasound-accelerated thrombolytic catheters were bilaterally placed in 25 (65.8%) patients. The median tissue plasminogen activator (tPA) dose for all patients in our study was 21.0 mg and the median infusion time was 15 hours. Measurements before and after treatment showed a decrease in pulmonary artery pressure. The median value of RV/LV diameter ratio decreased from 0.9 (0.7-1.1) at baseline to 0.7 (0-0.97) at 6-month follow-up (P=0.001) and pulmonary artery pressure from 61.4 ±16.7 to 37.2±9.1 mmHg (P=0.001). The median BNP level at baseline was 169 (29-721) pg/mL and 45.5 (0-328) pg/mL at 6 month follow-up (P=0.001). Of 38 patients with PE, one had intracranial hemorrage, one gastrointestinal bleeding and two developed puncture site bleeding. This prospective study provides alternative treatment option and an addition to the treatment algorithm for the management of pulmonary embolism.

  18. Flying saucer located at the basal septum.

    PubMed

    Akcay, Murat; Senkaya, Emine Bilen; Bilge, Mehmet; Bozkurt, Mehmet; Arslantas, Ugur; Karakas, Fatih

    2008-08-01

    Left ventricular thrombus formation is a frequent complication in patients with ischemic heart disease and is associated with a high risk of systemic embolization. Generally, thrombi localize at the apical segment. However, thrombus localized at the basal septum has not been reported yet. In this case, we discuss a flying saucer shaped mass located at the basal septum, which was later diagnosed as thrombus after anticoagulant therapy.

  19. Modeling of thermalization phenomena in coaxial plasma accelerators

    NASA Astrophysics Data System (ADS)

    Subramaniam, Vivek; Panneerchelvam, Premkumar; Raja, Laxminarayan L.

    2018-05-01

    Coaxial plasma accelerators are electromagnetic acceleration devices that employ a self-induced Lorentz force to produce collimated plasma jets with velocities ~50 km s‑1. The accelerator operation is characterized by the formation of an ionization/thermalization zone near gas inlet of the device that continually processes the incoming neutral gas into a highly ionized thermal plasma. In this paper, we present a 1D non-equilibrium plasma model to resolve the plasma formation and the electron-heavy species thermalization phenomena that take place in the thermalization zone. The non-equilibrium model is based on a self-consistent multi-species continuum description of the plasma with finite-rate chemistry. The thermalization zone is modelled by tracking a 1D gas-bit as it convects down the device with an initial gas pressure of 1 atm. The thermalization process occurs in two stages. The first is a plasma production stage, associated with a rapid increase in the charged species number densities facilitated by cathode surface electron emission and volumetric production processes. The production stage results in the formation of a two-temperature plasma with electron energies of ~2.5 eV in a low temperature background gas of ~300 K. The second, a temperature equilibration stage, is characterized by the energy transfer between the electrons and heavy species. The characteristic length scale for thermalization is found to be comparable to axial length of the accelerator thus putting into question the equilibrium magnetohydrodynamics assumption used in modeling coaxial accelerators.

  20. Accelerated effects of nano-ZnO on phosphorus removal by Chlorella vulgaris: Formation of zinc phosphate crystallites.

    PubMed

    Xiao, Huaixian; Liu, Na; Tian, Ke; Liu, Shixiang; Ge, Fei

    2018-09-01

    Nanoparticles have been reported to induce toxicity to aquatic organisms, however, their potential impacts on phosphorus removal from wastewater by algae are unclear. In this study, the effects of nanoparticle ZnO (nano-ZnO) on phosphate (PO 4 3- ) removal by a green alga Chlorella vulgaris were investigated. We found that PO 4 3- removal efficiency was accelerated with high concentrations of nano-ZnO (0.04-0.15mM) but reduced with low concentrations of nano-ZnO (0.005-0.04mM) compared to the control (without nano-ZnO), suggesting that PO 4 3- removal efficiency by C. vulgaris was related to nano-ZnO concentrations. Moreover, we observed changes of nano-ZnO morphology and detected element P on the surface of nano-ZnO by using transmission electronic microscopy (TEM) combined with energy dispersive X-ray spectroscopy (EDX), indicating that PO 4 3- was interacted with nano-ZnO or the dissolved Zn 2+ from nano-ZnO. Furthermore, we confirmed this interaction induced the formation of Zn 3 (PO 4 ) 2 crystallites sedimentation by employing X-ray diffraction analysis (XRD) and X-ray photoelectron spectroscopy (XPS), which finally accelerates the removal of PO 4 3- . Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Design of a Microwave Assisted Discharge Inductive Plasma Accelerator

    NASA Technical Reports Server (NTRS)

    Hallock, Ashley K.; Polzin, Kurt A.

    2010-01-01

    A new plasma accelerator concept that employs electrodeless plasma preionization and pulsed inductive acceleration is presented. Preionization is achieved through an electron cyclotron resonance discharge that produces a weakly-ionized plasma at the face of a conical theta pinch-shaped inductive coil. The presence of the preionized plasma allows for current sheet formation at lower discharge voltages than those found in other pulsed inductive accelerators. The location of an electron cyclotron resonance discharge can be controlled through the design of the applied magnetic field in the thruster. A finite-element model of the magnetic field was used as a design tool, allowing for the implementation of an arrangement of permanent magnets that yields a small volume of preionized propellant at the coil face. This allows for current sheet formation at the face of the inductive coil, minimizing the initial inductance of the pulse circuit and maximizing the potential efficiency of the new accelerator.

  2. In vivo imaging visualizes discoid platelet aggregations without endothelium disruption and implicates contribution of inflammatory cytokine and integrin signaling.

    PubMed

    Nishimura, Satoshi; Manabe, Ichiro; Nagasaki, Mika; Kakuta, Shigeru; Iwakura, Yoichiro; Takayama, Naoya; Ooehara, Jun; Otsu, Makoto; Kamiya, Akihide; Petrich, Brian G; Urano, Tetsumei; Kadono, Takafumi; Sato, Shinichi; Aiba, Atsu; Yamashita, Hiroshi; Sugiura, Seiryo; Kadowaki, Takashi; Nakauchi, Hiromitsu; Eto, Koji; Nagai, Ryozo

    2012-02-23

    The mechanism by which thrombotic vessel occlusion occurs independently of plaque development or endothelial cell (EC) disruption remains unclear, largely because of an inability to visualize the formation of thrombus, especially at the single-platelet level in real time. Here we demonstrate that rapidly developing thrombi composed of discoid platelets can be induced in the mesenteric capillaries, arterioles, and large-sized arteries of living mice, enabling characterization of the kinetics of thrombosis initiation and the multicellular interrelationships during thrombus development. Platelet aggregation without EC disruption was triggered by reactive oxygen species (ROS) photochemically induced by moderate power laser irradiation. The inflammatory cytokines TNF-α and IL-1 could be key components of the EC response, acting through regulation of VWF mobilization to the cell surface. Thrombus formation was then initiated by the binding of platelet GPIbα to endothelial VWF in our model, and this effect was inhibited by the ROS scavenger N-acetylcysteine. Actin linker talin-dependent activation of alphaIIb-beta3 integrin or Rac1 in platelets was required for late-phase thrombus stability. Our novel imaging technology illustrates the molecular mechanism underlying inflammation-based thrombus formation by discoid platelets on undisrupted ECs and suggests control of ROS could be a useful therapeutic target for the prevention of thrombotic diseases.

  3. Loss of Sirt3 accelerates arterial thrombosis by increasing formation of neutrophil extracellular traps and plasma tissue factor activity

    PubMed Central

    Gaul, Daniel S; Weber, Julien; van Tits, Lambertus J; Sluka, Susanna; Pasterk, Lisa; Reiner, Martin F; Calatayud, Natacha; Lohmann, Christine; Klingenberg, Roland; Pahla, Jürgen; Vdovenko, Daria; Tanner, Felix C; Camici, Giovanni G; Eriksson, Urs; Auwerx, Johan; Mach, François; Windecker, Stephan; Rodondi, Nicolas; Lüscher, Thomas F; Winnik, Stephan; Matter, Christian M

    2018-01-01

    Abstract Aims Sirtuin 3 (Sirt3) is a mitochondrial, nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase that reduces oxidative stress by activation of superoxide dismutase 2 (SOD2). Oxidative stress enhances arterial thrombosis. This study investigated the effects of genetic Sirt3 deletion on arterial thrombosis in mice in an inflammatory setting and assessed the clinical relevance of these findings in patients with ST-elevation myocardial infarction (STEMI). Methods and results Using a laser-induced carotid thrombosis model with lipopolysaccharide (LPS) challenge, in vivo time to thrombotic occlusion in Sirt3−/− mice (n = 6) was reduced by half compared to Sirt3+/+ wild-type (n = 8, P < 0.01) controls. Ex vivo analyses of whole blood using rotational thromboelastometry revealed accelerated clot formation and increased clot stability in Sirt3−/− compared to wild-type blood. rotational thromboelastometry of cell-depleted plasma showed accelerated clotting initiation in Sirt3−/− mice, whereas overall clot formation and firmness remained unaffected. Ex vivo LPS-induced neutrophil extracellular trap formation was increased in Sirt3−/− bone marrow-derived neutrophils. Plasma tissue factor (TF) levels and activity were elevated in Sirt3−/− mice, whereas plasma levels of other coagulation factors and TF expression in arterial walls remained unchanged. SOD2 expression in bone marrow -derived Sirt3−/− neutrophils was reduced. In STEMI patients, transcriptional levels of Sirt3 and its target SOD2 were lower in CD14+ leukocytes compared with healthy donors (n = 10 each, P < 0.01). Conclusions Sirt3 loss-of-function enhances experimental thrombosis in vivo via an increase of neutrophil extracellular traps and elevation of TF suggesting thrombo-protective effects of endogenous Sirt3. Acute coronary thrombosis in STEMI patients is associated with lower expression levels of SIRT3 and SOD2 in CD14+ leukocytes. Therefore

  4. Black-blood thrombus imaging (BTI): a contrast-free cardiovascular magnetic resonance approach for the diagnosis of non-acute deep vein thrombosis.

    PubMed

    Xie, Guoxi; Chen, Hanwei; He, Xueping; Liang, Jianke; Deng, Wei; He, Zhuonan; Ye, Yufeng; Yang, Qi; Bi, Xiaoming; Liu, Xin; Li, Debiao; Fan, Zhaoyang

    2017-01-18

    Deep vein thrombosis (DVT) is a common but elusive illness that can result in long-term disability or death. Accurate detection of thrombosis and assessment of its size and distribution are critical for treatment decision-making. In the present study, we sought to develop and evaluate a cardiovascular magnetic resonance (CMR) black-blood thrombus imaging (BTI) technique, based on delay alternating with nutation for tailored excitation black-blood preparation and variable flip angle turbo-spin-echo readout, for the diagnosis of non-acute DVT. METHODS: This prospective study was approved by institutional review board and informed consent obtained from all subjects. BTI was first conducted in 11 healthy subjects for parameter optimization and then conducted in 18 non-acute DVT patients to evaluate its diagnostic performance. Two clinically used CMR techniques, contrast-enhanced CMR venography (CE-MRV) and three dimensional magnetization prepared rapid acquisition gradient echo (MPRAGE), were also conducted in all patients for comparison. All images obtained from patients were analyzed on a per-segment basis. Using the consensus diagnosis of CE-MRV as the reference, the sensitivity (SE), specificity (SP), positive and negative predictive values (PPV and NPV), and accuracy (ACC) of BTI and MPRAGE as well as their diagnostic agreement with CE-MRV were calculated. Besides, diagnostic confidence and interreader diagnostic agreement were evaluated for all three techniques. BTI with optimized parameters effectively nulled the venous blood flow signal and allowed directly visualizing the thrombus within the black-blood lumen. Higher SE (90.4% vs 67.6%), SP (99.0% vs. 97.4%), PPV (95.4% vs. 85.6%), NPV (97.8% vs 92.9%) and ACC (97.4% vs. 91.8%) were obtained by BTI in comparison with MPRAGE. Good diagnostic confidence and excellent diagnostic and interreader agreements were achieved by BTI, which were superior to MPRAGE on detecting the chronic thrombus. BTI allows

  5. Ischemic Stroke: What Does the Histological Composition Tell Us About the Origin of the Thrombus?

    PubMed

    Sporns, Peter B; Hanning, Uta; Schwindt, Wolfram; Velasco, Aglaé; Minnerup, Jens; Zoubi, Tarek; Heindel, Walter; Jeibmann, Astrid; Niederstadt, Thomas Ulrich

    2017-08-01

    The introduction of stent retrievers allows for a complete extraction and histological analysis of human thrombi. Ischemic stroke is a major health issue, and differentiation of underlying causes is highly relevant to prevent recurrent stroke. Therefore, histopathologic analysis of the embolic clots after removal may provide valuable information about underlying pathologies. This study analyzes histological clot composition and aims to identify specific patterns that might help to distinguish causes of ischemic stroke. Patients with occlusion of the carotid-T or middle cerebral artery who underwent thrombectomy at our university medical center between December 2013 and February 2016 were included. Samples were histologically analyzed (hematoxylin and eosin, Elastica van Gieson, and Prussian blue), additionally immunohistochemistry for CD3, CD20, and CD68/KiM1P was performed. These data, along with additional clinical and interventional parameters, were compared for different stroke subtypes, as defined by the TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification. One hundred eighty-seven patients were included, of these, in 77 patients, cardioembolic; in 46 patients, noncardioembolic; and in 64 patients, cryptogenic pathogenesis was determined. Cardioembolic thrombi had higher proportions of fibrin/platelets ( P =0.027), less erythrocytes ( P =0.005), and more leucocytes ( P =0.026) than noncardioembolic thrombi. We observed a strong overlap of cryptogenic strokes and cardioembolic strokes concerning thrombus histology. The immunohistochemical parameters CD3, CD20, and CD68/KiM1P showed no statistically noticeable differences between stroke subtypes. Histological thrombus features vary significantly according to the underlying cause and may help to differentiate between cardioembolic and noncardioembolic stroke. In addition, our study supports the hypothesis that most cryptogenic strokes have a cardioembolic cause. © 2017 American Heart Association

  6. Canola and hydrogenated soybean oils accelerate ectopic bone formation induced by implantation of bone morphogenetic protein in mice.

    PubMed

    Hashimoto, Yoko; Mori, Mayumi; Kobayashi, Shuichiro; Hanya, Akira; Watanabe, Shin-Ichi; Ohara, Naoki; Noguchi, Toshihide; Kawai, Tatsushi; Okuyama, Harumi

    2014-01-01

    Canola oil (Can) and hydrogenated soybean oil (H2-Soy) are commonly used edible oils. However, in contrast to soybean oil (Soy), they shorten the survival of stroke-prone spontaneously hypertensive (SHRSP) rats. It has been proposed that the adverse effects of these oils on the kidney and testis are caused at least in part by dihydro-vitamin K (VK) 1 in H2-Soy and unidentified component(s) in Can. Increased intake of dihydro-VK1 is associated with decreased tissue VK2 levels and bone mineral density in rats and humans, respectively. The aim of the present study was to determine the effects of these oils on bone morphogenetic protein (BMP)-induced ectopic bone formation, which is promoted by VK2 deficiency, in relation to the role of VK in the γ-carboxylation of osteocalcin and matrix Gla protein. A crude extract of BMPs was implanted into a gap in the fascia of the femoral muscle in 5-week-old mice maintained on a Soy, Can, or H2-Soy diet. Newly formed bone volume, assessed by three-dimensional X-ray micro-computed tomography and three-dimensional reconstruction imaging for bone, was 4-fold greater in the Can and H2-Soy groups than in the Soy group. The plasma carboxylated osteocalcin (Gla-OC) and total OC (Gla-OC plus undercarboxylated osteocalcin [Glu-OC]) levels were significantly lower in the Can group than in the Soy group ( p < 0.05). However, these levels did not significantly differ between the H2-Soy and Soy groups. The plasma Gla-OC/Glu-OC ratio in the Can and H2-Soy groups was significantly lower (in Can; p = 0.044) or was almost significantly lower (in H2-Soy; p = 0.053) than that in the Soy group. In conclusion, Can and H2-Soy accelerated BMP-induced bone formation in mice to a greater extent than Soy. Further research is required to evaluate whether the difference in accelerated ectopic bone formation is associated with altered levels of VK2 and VK-dependent protein(s) among the three dietary groups.

  7. Mice Lacking the SLAM Family Member CD84 Display Unaltered Platelet Function in Hemostasis and Thrombosis

    PubMed Central

    Hofmann, Sebastian; Braun, Attila; Pozgaj, Rastislav; Morowski, Martina; Vögtle, Timo; Nieswandt, Bernhard

    2014-01-01

    Background Platelets are anuclear cell fragments derived from bone marrow megakaryocytes that safeguard vascular integrity by forming thrombi at sites of vascular injury. Although the early events of thrombus formation—platelet adhesion and aggregation—have been intensively studied, less is known about the mechanisms and receptors that stabilize platelet-platelet interactions once a thrombus has formed. One receptor that has been implicated in this process is the signaling lymphocyte activation molecule (SLAM) family member CD84, which can undergo homophilic interactions and becomes phosphorylated upon platelet aggregation. Objective The role of CD84 in platelet physiology and thrombus formation was investigated in CD84-deficient mice. Methods and Results We generated CD84-deficient mice and analyzed their platelets in vitro and in vivo. Cd84−/− platelets exhibited normal activation and aggregation responses to classical platelet agonists. Furthermore, CD84 deficiency did not affect integrin-mediated clot retraction and spreading of activated platelets on fibrinogen. Notably, also the formation of stable three-dimensional thrombi on collagen-coated surfaces under flow ex vivo was unaltered in the blood of Cd84−/− mice. In vivo, Cd84−/− mice exhibited unaltered hemostatic function and arterial thrombus formation. Conclusion These results show that CD84 is dispensable for thrombus formation and stabilization, indicating that its deficiency may be functionally compensated by other receptors or that it may be important for platelet functions different from platelet-platelet interactions. PMID:25551754

  8. HIF-1α and VEGF expression correlates with thrombus remodeling in cases of intravascular papillary endothelial hyperplasia

    PubMed Central

    Kim, Sunzoo; Jun, Jae Hun; Kim, Jeongshik; Kim, Do Won; Jang, Yong Hyun; Lee, Weon Ju; Chung, Ho Yun; Lee, Seok-Jong

    2013-01-01

    Intravascular papillary endothelial hyperplasia (IPEH) is histopathologically characterized by endothelium-lined papillary structures encircling an acellular fibrin core. The process of IPEH pathogenesis is unclear. The purpose of our study was to identify histopathological and immunohistochemical characteristics of IPEH to better understand the pathogenesis of this disease. After reviewing microscopic and medical records from Kyungpook National University Hospital, we selected 16 cases of IPEH. Masson’s trichrome and immunohistochemical staining as well as hematoxylin-eosin staining for 16 cases of IPH were performed. Immunohistochemical studies included CD31, CD68, mast cell tryptase, hypoxia-inducible factor-1 (HIF-1α), and vascular endothelial growth factor (VEGF). Sections from all our cases showed three distinct histological regions including a papillary portion with hyalinized fibrous or fibroblastic cores, an area containing an unorganized thrombus, and organization area with an ingrowth of endothelial cells, myofibroblasts, and fibroblasts. In the organization area, HIF-1α-positive cells were identified in the loose connective tissue. Endothelial cells forming vascular channels were negative for HIF-1α while VEGF was highly expressed in both interstitial mononuclear and endothelial cells. In the papillary portion, the cellular cores were strongly positive for both HIF-1α and VEGF, but the acellular cores were negative. Our investigation confirmed that IPEH is a reactive lesion that incidentally arises during the organization process of older thrombi. It was also found that HIF-1α and VEGF expression was dependent on the thrombus remodeling stage in cases of IPEH. PMID:24294378

  9. Use of multidetector-row computed tomography scan to detect pannus formation in prosthetic mechanical aortic valves

    PubMed Central

    Aladmawi, Mohamed A.; Vriz, Olga; Galzerano, Domenico

    2017-01-01

    Obstruction of a mechanical aortic valve by pannus formation at the subvalvular level is a major long-term complication of aortic valve replacement (AVR). In fact, pannus is sometime difficult to differentiate from patient-prosthesis mismatch or valve thrombosis. In most cases cine-angiography and echocardiography, either transthoracic or transesophageal, cannot correctly visualize the complication when the leaflets show a normal mobility. Recent technological refinements made this difficult diagnosis possible by ECG-gated computed tomography (CT) scan which shows adequate images in 90% of the cases and can differentiate pannus from fresh and organized thrombus. PMID:28540078

  10. Effects of different shear rates on the attachment and detachment of platelet thrombi.

    PubMed

    Shi, Xiaofeng; Yang, Jichun; Huang, Jiansong; Long, Zhangbiao; Ruan, Zheng; Xiao, Bing; Xi, Xiaodong

    2016-03-01

    Thrombosis and hemostasis take place in flowing blood, which generates shear forces. The effect of different shear rates, particularly pathological forces, on platelet thrombus formation remains to be fully elucidated. The present study observed the morphological characteristics and hierarchical structure of thrombi on the collagen surface at a wide range of wall shear rates (WSRs) and examined the underlying mechanisms. Calcein AM‑labeled whole blood was perfused over a collagen‑coated surface at different shear rates set by a Bioflux 200 microfluidic device and the thrombi formed were assessed for area coverage, the height and the hierarchical structure defined by the extent of platelet activation and packing density. The factors that affect thrombus formation were also investigated. Platelet thrombus formation varied under different WSRs, for example, dispersed platelet adhesion mixed with erythrocytes was observed at 125‑250 s(‑1), extensive and thin platelet thrombi were observed at 500‑1,500 s(‑1), and sporadic, thick thrombi were observed at pathological WSRs of 2,500‑5,000 s(‑1), which showed a tendency to be shed. With increasing WSRs, the height of the thrombi showed an increasing linear trend, whereas the total fluorescence intensity and area of the thrombi exhibited a parabolic curve‑like change, with a turning point at a WSR of 2,500 s(‑1). The number of thrombi, the average fluorescence intensity and the area per thrombus showed similar trends, with an initial upwards incline followed by a decline. The thrombi formed at higher WSRs had a thicker shell, which led to a more densely packed core. Platelet thrombus formation under shear‑flow was regulated by the adhesive strength, which was mediated by receptor‑ligand interaction, the platelet deposition induced by shear rates and the detachment by the dynamic force of flow. This resulted in a balance between thrombus attachment, including adhesion and aggregation, and detachment

  11. An antithrombotic fucoidan, unlike heparin, does not prolong bleeding time in a murine arterial thrombosis model: a comparative study of Undaria pinnatifida sporophylls and Fucus vesiculosus.

    PubMed

    Min, Soon-Ki; Kwon, Oh-Choon; Lee, Sub; Park, Ki-Hyuk; Kim, Jong-Ki

    2012-05-01

    The antithrombotic activities and bleeding effects of selected fucoidans (source from either Undaria pinnatifida sporophylls or from Fucus vesiculosus) have been compared with heparin in the ferric chloride-induced arterial thrombus mouse model. Thrombosis was induced by applying 5% ferric chloride for 3 min on the carotid artery region of Balb/c mouse. Five minutes prior to thrombus induction, mice were infused through the tail vein with either saline (control) or polysaccharides. Either fucoidan or heparin was dosed at 0.1, 1.25, 2.5, 5.0, 10, 25, or 50 mg/kg intravenously (i.v.) The carotid blood flow was monitored until more than 60 min post-thrombus induction. Mouse tail transection bleeding time was measured up to 60 min after making a cut in the mouse tail. Both antithrombotic and bleeding effects were observed in a dose-dependent manner for both fucoidans and heparin. Thrombus formation was totally (reflected by Doppler flow meter) inhibited at either 5 or 50 mg/kg of unfractionated Undaria fucoidan or a low-molecular-weight Undaria fucoidan fraction, respectively, without prolonging the time-to-stop bleeding compared with the control (p < 0.01). The total inhibition of thrombus formation was observed for unfractionated Fucus fucoidan at 25 mg/kg where the time-to-stop bleeding was still significantly prolonged, by as much as 8 ± 1.7 min (p < 0.02). In contrast the heparin-treated group showed total inhibition of thrombus formation even at a small dose of 0.8 mg/kg (400 IU) at which bleeding continued until 60 min. In conclusion algal fucoidans are highly antithrombotic without potential haemorrhagic effects compared with heparin in the arterial thrombus model, but this property differs from algal species to species, and from the molecular structure of fucoidans. Copyright © 2011 John Wiley & Sons, Ltd.

  12. Bax deficiency prolongs cerebellar neurogenesis, accelerates medulloblastoma formation and paradoxically increases both malignancy and differentiation.

    PubMed

    Garcia, I; Crowther, A J; Gama, V; Miller, C R; Miller, C Ryan; Deshmukh, M; Gershon, T R

    2013-05-02

    Neurogenesis requires negative regulation through differentiation of progenitors or their programmed cell death (PCD). Growth regulation is particularly important in the postnatal cerebellum, where excessive progenitor proliferation promotes medulloblastoma, the most common malignant brain tumor in children. We present evidence that PCD operates alongside differentiation to regulate cerebellar granule neuron progenitors (CGNPs) and to prevent medulloblastoma. Here, we show that genetic deletion of pro-apoptotic Bax disrupts regulation of cerebellar neurogenesis and promotes medulloblastoma formation. In Bax(-/-) mice, the period of neurogenesis was extended into the third week of postnatal life, and ectopic neurons and progenitors collected in the molecular layer of the cerebellum and adjacent tectum. Importantly, genetic deletion of Bax in medulloblastoma-prone ND2:SmoA1 transgenic mice greatly accelerated tumorigenesis. Bax-deficient medulloblastomas exhibited strikingly distinct pathology, with reduced apoptosis, increased neural differentiation and tectal migration. Comparing Bax(+/+) and Bax(-/-) medulloblastomas, we were able to identify upregulation of Bcl-2 and nuclear exclusion of p27 as tumorigenic changes that are required to mitigate the tumor suppressive effect of Bax. Studies on human tumors confirmed the importance of modulating Bax in medulloblastoma pathogenesis. Our results demonstrate that Bax-dependent apoptosis regulates postnatal cerebellar neurogenesis, suppresses medulloblastoma formation and imposes selective pressure on tumors that form. Functional resistance to Bax-mediated apoptosis, required for medulloblastoma tumorigenesis, may be a tumor-specific vulnerability to be exploited for therapeutic benefit.

  13. Electron acceleration by turbulent plasmoid reconnection

    NASA Astrophysics Data System (ADS)

    Zhou, X.; Büchner, J.; Widmer, F.; Muñoz, P. A.

    2018-04-01

    In space and astrophysical plasmas, like in planetary magnetospheres, as that of Mercury, energetic electrons are often found near current sheets, which hint at electron acceleration by magnetic reconnection. Unfortunately, electron acceleration by reconnection is not well understood yet, in particular, acceleration by turbulent plasmoid reconnection. We have investigated electron acceleration by turbulent plasmoid reconnection, described by MHD simulations, via test particle calculations. In order to avoid resolving all relevant turbulence scales down to the dissipation scales, a mean-field turbulence model is used to describe the turbulence of sub-grid scales and their effects via a turbulent electromotive force (EMF). The mean-field model describes the turbulent EMF as a function of the mean values of current density, vorticity, magnetic field as well as of the energy, cross-helicity, and residual helicity of the turbulence. We found that, mainly around X-points of turbulent reconnection, strongly enhanced localized EMFs most efficiently accelerated electrons and caused the formation of power-law spectra. Magnetic-field-aligned EMFs, caused by the turbulence, dominate the electron acceleration process. Scaling the acceleration processes to parameters of the Hermean magnetotail, electron energies up to 60 keV can be reached by turbulent plasmoid reconnection through the thermal plasma.

  14. Endothelial progenitor cells inhibit platelet function in a P-selectin-dependent manner.

    PubMed

    Abou-Saleh, Haissam; Hachem, Ahmed; Yacoub, Daniel; Gillis, Marc-Antoine; Merhi, Yahye

    2015-05-07

    The role of endothelial progenitor cells (EPCs) in vascular repair is related to their recruitment at the sites of injury and their interaction with different components of the circulatory system. We have previously shown that EPCs bind and inhibit platelet function and impair thrombus formation via prostacyclin secretion, but the role of EPC binding to platelet P-selectin in this process has not been fully characterized. In the present study, we assessed the impact of EPCs on thrombus formation and we addressed the implication of P-selectin in this process. EPCs were generated from human peripheral blood mononuclear cells cultured on fibronectin in conditioned media. The impact of EPCs on platelet aggregation and thrombus formation was investigated in P-selectin deficient (P-sel(-/-)) mice and their wild-type (WT) counterparts. EPCs significantly and dose-dependently impaired collagen-induced whole blood platelet aggregation in WT mice, whereas no effects were observed in P-sel(-/-) mice. Moreover, in a ferric chloride-induced arterial thrombosis model, infusion of EPCs significantly reduced thrombus formation in WT, but not in P-sel(-/-) mice. Furthermore, the relative mass of thrombi generated in EPC-treated P-sel(-/-) mice were significantly larger than those in EPC-treated WT mice, and the number of EPCs recruited within the thrombi and along the arterial wall was reduced in P-sel(-/-) mice as compared to WT mice. This study shows that EPCs impair platelet aggregation and reduce thrombus formation via a cellular mechanism involving binding to platelet P-selectin. These findings add new insights into the role of EPC-platelet interactions in the regulation of thrombotic events during vascular repair.

  15. A novel thromboxane receptor antagonist, nstpbp5185, inhibits platelet aggregation and thrombus formation in animal models.

    PubMed

    Huang, Shiu-Wen; Kuo, Heng-Lan; Hsu, Ming-Tsung; Tseng, Yufeng Jane; Lin, Shu-Wha; Kuo, Sheng-Chu; Peng, Hui-Chin; Lien, Jin-Cherng; Huang, Tur-Fu

    2016-08-01

    A novel benzimidazole derivative, nstpbp5185, was discovered through in vitro and in vivo evaluations for antiplatelet activity. Thromaboxane receptor (TP) is important in vascular physiology, haemostasis and pathophysiological thrombosis. Nstpbp5185 concentration-dependently inhibited human platelet aggregation caused by collagen, arachidonic acid and U46619. Nstpbp5185 caused a right-shift of the concentration-response curve of U46619 and competitively inhibited the binding of 3H-SQ-29548 to TP receptor expressed on HEK-293 cells, with an IC50 of 0.1 µM, indicating that nstpbp5185 is a TP antagonist. In murine thrombosis models, nstpbp5185 significantly prolonged the latent period in triggering platelet plug formation in mesenteric and FeCl3-induced thrombi formation, and increased the survival rate in pulmonary embolism model with less bleeding than aspirin. This study suggests nstpbp5185, an orally selective anti-thrombotic agent, acting through blockade of TXA2 receptor, may be efficacious for prevention or treatment of pathologic thrombosis.

  16. Adult Wilms tumor with inferior vena cava thrombus and distal deep vein thrombosis - a case report and literature review.

    PubMed

    Ratajczyk, Krzysztof; Czekaj, Adrian; Rogala, Joanna; Kowal, Pawel

    2018-02-23

    Adult Wilms tumor (WT, nephroblastoma) is a rare, but well-described renal neoplasm. Although inferior vena cava tumor thrombosis is present in up to 10% of Wilms tumors in childhood, only few cases of this clinical manifestation in adults have been reported. To the best of our knowledge, this is the first case of adult WT infiltrating into inferior vena cava (IVC) with concomitant distal deep vein thrombosis. A 28-year-old male patient with gross hematuria and right flank pain was diagnosed with right kidney tumor penetrating to IVC. Preoperatively, acute distal thrombosis in inferior vena cava and lower extremities veins occurred. Right radical nephrectomy with tumor thrombectomy via cavotomy was performed. In order to prevent pulmonary embolism, IVC was ligated below left renal vein level. Histopathological examination revealed a triphasic nephroblastoma without anaplastic features. Postoperatively, patient was diagnosed with metastatic liver disease, which was treated with two lines of chemotherapy followed by radiotherapy with achievement of complete response. Adult WT occurs usually in young patients, under 40 years of age. Neoadjuvant chemotherapy proved to be effective in children, resulting with tumor shrinkage and venous tumor thrombus regression. Therefore, percutaneous biopsy should be always considered in young patients presenting with renal tumor invading venous system. IVC ligation is a safe treatment option in the event of complete inferior vena cava occlusion due to distal thrombosis concomitant to tumor thrombus, provided collateral venous pathways are well-developed.

  17. Formation of electrostatic structures by wakefield acceleration in ultrarelativistic plasma flows: Electron acceleration to cosmic ray energies

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dieckmann, M.E.; Shukla, P.K.; Eliasson, B.

    2006-06-15

    The ever increasing performance of supercomputers is now enabling kinetic simulations of extreme astrophysical and laser produced plasmas. Three-dimensional particle-in-cell (PIC) simulations of relativistic shocks have revealed highly filamented spatial structures and their ability to accelerate particles to ultrarelativistic speeds. However, these PIC simulations have not yet revealed mechanisms that could produce particles with tera-electron volt energies and beyond. In this work, PIC simulations in one dimension (1D) of the foreshock region of an internal shock in a gamma ray burst are performed to address this issue. The large spatiotemporal range accessible to a 1D simulation enables the self-consistent evolutionmore » of proton phase space structures that can accelerate particles to giga-electron volt energies in the jet frame of reference, and to tens of tera-electron volt in the Earth's frame of reference. One potential source of ultrahigh energy cosmic rays may thus be the thermalization of relativistically moving plasma.« less

  18. [Tumor thrombus arising from the superior vena cava and extending into the right atrium in a patient with advanced testicular germ cell tumor].

    PubMed

    Miyake, Makito; Fujimoto, Kiyohide; Matsushita, Chie; Chihara, Yoshitomo; Tanaka, Masahiro; Hirayama, Akihide; Hirao, Yoshihiko; Uemura, Hirotsugu

    2009-06-01

    A 24-year-old man was referred to our hospital with a painless mass on the left side of his neck. Ultrasonography detected right testicular tumor and computerized tomography scanning revealed a left supraclavicular lymph node mass and bulky retroperitoneal lymph node mass. He initially underwent right high orchiectomy, combination chemotherapy and retroperitoneal lymph node dissection for advanced testicular non-seminomatous germ cell tumor. Six years later, late relapse was detected in the lung. After complete remission of the lung metastasis with chemotherapy, the serum alpha-fetoprotein began to increase because of superior vena caval thrombus extending into the right atrium. Emergency surgical excision was performed successfully using extracorporeal circulation to prevent pulmonary embolism and the resected specimen pathologically revealed adenocarcinoma interpreted as teratoma malignant transformation. Adjuvant chemotherapy consisting of paclitaxel, ifosfamide and nedaplatin were administered for subsequent slight elevation of serum F-human chorionic gonadotropin beta, resulting in successful normalization again. Later, he suddenly died of cerebral infarction without any evidence of recurrence 138 months after his initial presentation. We report herein an extremely uncommon case of advanced testicular germ cell tumor with development of superior vena caval thrombus extending into the right atrium.

  19. Controlled Delivery of a Focal Adhesion Kinase Inhibitor Results in Accelerated Wound Closure with Decreased Scar Formation.

    PubMed

    Ma, Kun; Kwon, Sun Hyung; Padmanabhan, Jagannath; Duscher, Dominik; Trotsyuk, Artem A; Dong, Yixiao; Inayathullah, Mohammed; Rajadas, Jayakumar; Gurtner, Geoffrey C

    2018-05-15

    Formation of scars following wounding or trauma represents a significant healthcare burden costing the economy billions of dollars every year. Activation of focal adhesion kinase (FAK) has been shown to play a pivotal role in transducing mechanical signals to elicit fibrotic responses and scar formation during wound repair. We have previously shown that inhibition of FAK using local injections of a small molecule FAK inhibitor (FAKI) can attenuate scar development in a hypertrophic scar model. Clinical translation of FAKI therapy has been challenging, however, due to the lack of an effective drug delivery system for extensive burn injuries, blast injuries, and large excisional injuries. To address this issue, we have developed a pullulan collagen-based hydrogel to deliver FAKI to excisional and burn wounds in mice. Specifically, two distinct drug-laden hydrogels were developed for rapid or sustained release of FAKI for treatment of burn wounds and excisional wounds, respectively. Controlled delivery of FAKI via pullulan collagen hydrogels accelerated wound healing, reduced collagen deposition and activation of scar forming myofibroblasts in both wound healing models. Our study highlights a biomaterial-based drug delivery approach for wound and scar management that has significant translational implications. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Functional genomics in zebrafish permits rapid characterization of novel platelet membrane proteins.

    PubMed

    O'Connor, Marie N; Salles, Isabelle I; Cvejic, Ana; Watkins, Nicholas A; Walker, Adam; Garner, Stephen F; Jones, Chris I; Macaulay, Iain C; Steward, Michael; Zwaginga, Jaap-Jan; Bray, Sarah L; Dudbridge, Frank; de Bono, Bernard; Goodall, Alison H; Deckmyn, Hans; Stemple, Derek L; Ouwehand, Willem H

    2009-05-07

    In this study, we demonstrate the suitability of the vertebrate Danio rerio (zebrafish) for functional screening of novel platelet genes in vivo by reverse genetics. Comparative transcript analysis of platelets and their precursor cell, the megakaryocyte, together with nucleated blood cell elements, endothelial cells, and erythroblasts, identified novel platelet membrane proteins with hitherto unknown roles in thrombus formation. We determined the phenotype induced by antisense morpholino oligonucleotide (MO)-based knockdown of 5 of these genes in a laser-induced arterial thrombosis model. To validate the model, the genes for platelet glycoprotein (GP) IIb and the coagulation protein factor VIII were targeted. MO-injected fish showed normal thrombus initiation but severely impaired thrombus growth, consistent with the mouse knockout phenotypes, and concomitant knockdown of both resulted in spontaneous bleeding. Knockdown of 4 of the 5 novel platelet proteins altered arterial thrombosis, as demonstrated by modified kinetics of thrombus initiation and/or development. We identified a putative role for BAMBI and LRRC32 in promotion and DCBLD2 and ESAM in inhibition of thrombus formation. We conclude that phenotypic analysis of MO-injected zebrafish is a fast and powerful method for initial screening of novel platelet proteins for function in thrombosis.

  1. Application of Plasma Waveguides to High Energy Accelerators

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Milchberg, Howard M

    2013-03-30

    The eventual success of laser-plasma based acceleration schemes for high-energy particle physics will require the focusing and stable guiding of short intense laser pulses in reproducible plasma channels. For this goal to be realized, many scientific issues need to be addressed. These issues include an understanding of the basic physics of, and an exploration of various schemes for, plasma channel formation. In addition, the coupling of intense laser pulses to these channels and the stable propagation of pulses in the channels require study. Finally, new theoretical and computational tools need to be developed to aid in the design and analysismore » of experiments and future accelerators. Here we propose a 3-year renewal of our combined theoretical and experimental program on the applications of plasma waveguides to high-energy accelerators. During the past grant period we have made a number of significant advances in the science of laser-plasma based acceleration. We pioneered the development of clustered gases as a new highly efficient medium for plasma channel formation. Our contributions here include theoretical and experimental studies of the physics of cluster ionization, heating, explosion, and channel formation. We have demonstrated for the first time the generation of and guiding in a corrugated plasma waveguide. The fine structure demonstrated in these guides is only possible with cluster jet heating by lasers. The corrugated guide is a slow wave structure operable at arbitrarily high laser intensities, allowing direct laser acceleration, a process we have explored in detail with simulations. The development of these guides opens the possibility of direct laser acceleration, a true miniature analogue of the SLAC RF-based accelerator. Our theoretical studies during this period have also contributed to the further development of the simulation codes, Wake and QuickPIC, which can be used for both laser driven and beam driven plasma based acceleration

  2. Accelerated cure of phenol-formaldehyde resins : studies with model compounds

    Treesearch

    Anthony H. Conner; Linda F. Lorenz; Kolby C. Hirth

    2002-01-01

    2-Hydroxymethylphenol (2-HMP) and 4-hydroxymethylphenol (4-HMP) were used as model compounds to study the reactions that occur during cure of phenol-formaldehyde (PF) resin to which cure accelerators (ethyl formate, propylene carbonate, g-butyrolactone, and triacetin) have been added. The addition of cure accelerators significantly increased the rate of condensation...

  3. Bacoside-A, an anti-amyloid natural substance, inhibits membrane disruption by the amyloidogenic determinant of prion protein through accelerating fibril formation.

    PubMed

    Malishev, Ravit; Nandi, Sukhendu; Kolusheva, Sofiya; Shaham-Niv, Shira; Gazit, Ehud; Jelinek, Raz

    2016-09-01

    Bacosides, class of compounds extracted from the Bacopa monniera plant, exhibit interesting therapeutic properties, particularly enhancing cognitive functions and putative anti-amyloid activity. We show that bacoside-A exerted significant effects upon fibrillation and membrane interactions of the amyloidogenic fragment of the prion protein [PrP(106-126)]. Specifically, when co-incubated with PrP(106-126), bacoside-A accelerated fibril formation in the presence of lipid bilayers and in parallel inhibited bilayer interactions of the peptide aggregates formed in solution. These interesting phenomena were studied by spectroscopic and microscopic techniques, which suggest that bacoside A-promoted fibrillation reduced the concentration of membrane-active pre-fibrillar species of the prion fragment. This study suggests that induction of fibril formation and corresponding inhibition of membrane interactions are likely the underlying factors for ameliorating amyloid protein toxicity by bacoside-A. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Left atrial appendage myxofibrosarcoma: A rare masquerader of myxoma and thrombus-"all that glitters is not gold".

    PubMed

    Khan, Muhammad Shoaib; Reddy, Sahadev; Lombardi, Richard; Isabel, Pitti; Mcgregor, Walter E; Tang, Bang; Gabriel, George; Biederman, Robert W

    2018-02-01

    Left atrial appendage mass can occasionally pose a serious challenge to physicians to identify the nature of the mass with the aid of imaging techniques. We present a case of 67-year-old man, who was evaluated for suspected left atria myxoma. Transesophageal echocardiography revealed a heterogeneous density originating from left atrial appendage, thought to be most consistent with a myxoma. Cardiac magnetic resonance imaging, uncharacteristically, gave an equivocal picture, suggesting the mass to be a myxoma on initial imaging and a thrombus with evidence of liquefaction necrosis following postcontrast enhancement. Surprisingly, histopathology of the mass following its surgical excision yielded a rare diagnosis of myxofibrosarcoma. © 2017, Wiley Periodicals, Inc.

  5. Numerical Simulation of Thrombotic Occlusion in Tortuous Arterioles

    PubMed Central

    Feng, Zhi-Gang; Cortina, Miguel; Chesnutt, Jennifer KW; Han, Hai-Chao

    2017-01-01

    Tortuous microvessels alter blood flow and stimulate thrombosis but the physical mechanisms are poorly understood. Both tortuous microvessels and abnormally large platelets are seen in diabetic patients. Thus, the objective of this study was to determine the physical effects of arteriole tortuosity and platelet size on the microscale processes of thrombotic occlusion in microvessels. A new lattice-Boltzmann method-based discrete element model was developed to simulate the fluid flow field with fluid-platelet coupling, platelet interactions, thrombus formation, and thrombotic occlusion in tortuous arterioles. Our results show that vessel tortuosity creates high shear stress zones that activate platelets and stimulate thrombus formation. The growth rate depends on the level of tortuosity and the pressure and flow boundary conditions. Once thrombi began to form, platelet collisions with thrombi and subsequent activations were more important than tortuosity level. Thrombus growth narrowed the channel and reduced the flow rate. Larger platelet size leads to quicker decrease of flow rate due to larger thrombi that occluded the arteriole. This study elucidated the important roles that tortuosity and platelet size play in thrombus formation and occlusion in arterioles. PMID:29327739

  6. Role of thromboelastography and rapid thromboelastography to assess the pharmacodynamic effects of vitamin K antagonists.

    PubMed

    Franchi, Francesco; Hammad, Jafri Syed; Rollini, Fabiana; Tello-Montoliu, Antonio; Patel, Ronakkumar; Darlington, Andrew; Kraemer, Dale F; Cho, Jung Rae; DeGroat, Christopher; Bhatti, Mona; Taha, Mohamad; Angiolillo, Dominick J

    2015-07-01

    Thromboelastography (TEG) measures the effects of antithrombotic agents by assessing global functional clotting status by evaluating the viscoelastic properties of in vitro clot formation. Recently, rapid TEG (r-TEG), which uses tissue factor in addition to standard kaolin to accelerate activation of the clotting cascade, has been proposed to obtain more immediate results. The correlation between results of TEG or r-TEG with international normalized ratio (INR) in patients on vitamin K antagonist (VKA) therapy has not been explored and represents the aim of this study. Patients on chronic therapy with VKAs (n = 100) were included in an observational prospective pharmacodynamic study. The correlation between TEG parameters, in particular markers of thrombus generation [Reaction time (R), maximum rate of thrombus generation (MRTG), and time to maximum rate of thrombus generation (TMRTG)], and INR values as well as the concordance between these parameters and therapeutic INR ranges were evaluated. In addition, in a subgroup of subjects (n = 17), the correlation of r-TEG parameters with TEG parameters and INR values was also assessed. No correlation was found between INR and TEG parameters of thrombus generation, in particular between INR and R (r = 0.189, p = 0.06), MRTG (r = -0.027, p = 0.79), and TMRTG (r = 0.188, p = 0.06). Further, no concordance was found between these parameters and recommended INR ranges. Significant Spearman correlations were found between INR and activated clotting time (rS = 0.546, p < 0.001), r-R (rS = 0.572, p = 0.017), and r-TMRTG (rS = 0.510, p = 0.037), but not r-MRTG (rS = 0.131, p = 0.617). Results were obtained in 24 ± 6 versus 12 ± 4 min with TEG and r-TEG, respectively (p < 0.001). In patients on chronic VKA therapy, TEG is not a useful tool to evaluate VKA anticoagulant effect, compared with standard INR measurements. However, r-TEG parameters of thrombus generation correlate with INR levels, suggesting a possible role of this

  7. Frataxin Accelerates [2Fe-2S] Cluster Formation on the Human Fe–S Assembly Complex

    PubMed Central

    Fox, Nicholas G.; Das, Deepika; Chakrabarti, Mrinmoy; Lindahl, Paul A.; Barondeau, David P.

    2015-01-01

    Iron–sulfur (Fe–S) clusters function as protein cofactors for a wide variety of critical cellular reactions. In human mitochondria, a core Fe–S assembly complex [called SDUF and composed of NFS1, ISD11, ISCU2, and frataxin (FXN) proteins] synthesizes Fe–S clusters from iron, cysteine sulfur, and reducing equivalents and then transfers these intact clusters to target proteins. In vitro assays have relied on reducing the complexity of this complicated Fe–S assembly process by using surrogate electron donor molecules and monitoring simplified reactions. Recent studies have concluded that FXN promotes the synthesis of [4Fe-4S] clusters on the mammalian Fe–S assembly complex. Here the kinetics of Fe–S synthesis reactions were determined using different electron donation systems and by monitoring the products with circular dichroism and absorbance spectroscopies. We discovered that common surrogate electron donor molecules intercepted Fe–S cluster intermediates and formed high-molecular weight species (HMWS). The HMWS are associated with iron, sulfide, and thiol-containing proteins and have properties of a heterogeneous solubilized mineral with spectroscopic properties remarkably reminiscent of those of [4Fe-4S] clusters. In contrast, reactions using physiological reagents revealed that FXN accelerates the formation of [2Fe-2S] clusters rather than [4Fe-4S] clusters as previously reported. In the preceding paper [Fox, N. G., et al. (2015) Biochemistry 54, DOI: 10.1021/bi5014485], [2Fe-2S] intermediates on the SDUF complex were shown to readily transfer to uncomplexed ISCU2 or apo acceptor proteins, depending on the reaction conditions. Our results indicate that FXN accelerates a rate-limiting sulfur transfer step in the synthesis of [2Fe-2S] clusters on the human Fe–S assembly complex. PMID:26016518

  8. Frataxin Accelerates [2Fe-2S] Cluster Formation on the Human Fe-S Assembly Complex.

    PubMed

    Fox, Nicholas G; Das, Deepika; Chakrabarti, Mrinmoy; Lindahl, Paul A; Barondeau, David P

    2015-06-30

    Iron-sulfur (Fe-S) clusters function as protein cofactors for a wide variety of critical cellular reactions. In human mitochondria, a core Fe-S assembly complex [called SDUF and composed of NFS1, ISD11, ISCU2, and frataxin (FXN) proteins] synthesizes Fe-S clusters from iron, cysteine sulfur, and reducing equivalents and then transfers these intact clusters to target proteins. In vitro assays have relied on reducing the complexity of this complicated Fe-S assembly process by using surrogate electron donor molecules and monitoring simplified reactions. Recent studies have concluded that FXN promotes the synthesis of [4Fe-4S] clusters on the mammalian Fe-S assembly complex. Here the kinetics of Fe-S synthesis reactions were determined using different electron donation systems and by monitoring the products with circular dichroism and absorbance spectroscopies. We discovered that common surrogate electron donor molecules intercepted Fe-S cluster intermediates and formed high-molecular weight species (HMWS). The HMWS are associated with iron, sulfide, and thiol-containing proteins and have properties of a heterogeneous solubilized mineral with spectroscopic properties remarkably reminiscent of those of [4Fe-4S] clusters. In contrast, reactions using physiological reagents revealed that FXN accelerates the formation of [2Fe-2S] clusters rather than [4Fe-4S] clusters as previously reported. In the preceding paper [Fox, N. G., et al. (2015) Biochemistry 54, DOI: 10.1021/bi5014485], [2Fe-2S] intermediates on the SDUF complex were shown to readily transfer to uncomplexed ISCU2 or apo acceptor proteins, depending on the reaction conditions. Our results indicate that FXN accelerates a rate-limiting sulfur transfer step in the synthesis of [2Fe-2S] clusters on the human Fe-S assembly complex.

  9. Overexpression of the Cell Cycle Inhibitor p16INK4a Promotes a Prothrombotic Phenotype Following Vascular Injury in Mice

    PubMed Central

    Cardenas, Jessica C.; Owens, A. Phillip; Krishnamurthy, Janakiraman; Sharpless, Norman E.; Whinna, Herbert C.; Church, Frank C.

    2011-01-01

    Objective Age-associated cellular senescence is thought to promote vascular dysfunction. p16INK4a is a cell cycle inhibitor that promotes senescence and is upregulated during normal aging. In this study, we examine the contribution of p16INK4a overexpression on venous thrombosis. Methods and Results Mice overexpressing p16INK4a were studied with four different vascular injury models: (1) ferric chloride (FeCl3) and (2) Rose Bengal to induce saphenous vein thrombus formation; (3) FeCl3 and vascular ligation to examine thrombus resolution; and (4) LPS administration to initiate inflammation-induced vascular dysfunction. p16INK4a transgenic mice had accelerated occlusion times (13.1 ± 0.4 min) compared to normal controls (19.7 ± 1.1 min) in the FeCl3 model and 12.7 ± 2.0 and 18.6 ± 1.9, respectively in the Rose Bengal model. Moreover, overexpression of p16INK4a delayed thrombus resolution compared to normal controls. In response to LPS treatment, the p16INK4a transgenic mice showed enhanced thrombin generation in plasma-based calibrated automated thrombography (CAT) assays. Finally, bone marrow transplantation studies suggested increased p16INK4a expression in hematopoietic cells contributes to thrombosis, demonstrating a role for p16INK4a expression in venous thrombosis. Conclusions Venous thrombosis is augmented by overexpression of the cellular senescence gene p16INK4a. PMID:21233453

  10. A 1.1mm AzTEC Survey Tracing Accelerated Galaxy Formation Towards a Protocluster at z 3.8

    NASA Astrophysics Data System (ADS)

    Hughes, David H.; Montana, A.; Aretxaga, I.; Plionis, M.; Porras, A.; Wagg, J.; Gaztanaga, E.; Huang, J.; Fazio, G.; Wilson, G.; Yun, M.; Lowenthal, J.; Perera, T.; Austermann, J.; Scott, K.; Dunlop, J.; Ivison, R.; Stevens, J.; Smail, I.; Appleton, P.

    2006-12-01

    Aztec has recently conducted a sensitive, wide-area (300 sq. Armin's) continuum survey at 1.1mm using the 15-m James Clerk Maxwell Telescope towards 4C41.17, a powerful high-redshift (z 3.8) radio galaxy. These Aztec data, which cover an area >40 times larger than our previous SCUBA survey, reveal a significant over-density of luminous, massive dust-enshrouded galaxies, compared to the results from lower-redshift blank-field sub-mm surveys. One natural interpretation of these new AzTEC data is that the over-density is tracing a large (5 x 5 Mpc) "proto-cluster" structure at z 3.8 associated with the environment of 4C41.17, within which the formation of ultra-luminous starburst galaxies (with rest-frame FIR luminosities >5 x 1012 Lsun or SFRs > 500 Msun/yr) is taking place at an accelerated rate. Proving the physical association of these massive optically-faint starbursts with the environment of this high-z AGN, and not with the blank-field sub-mm population, for which 50% of the population lies at 1.9 < z < 2.9, remains an outstanding problem. In this presentation we will describe the AzTEC survey, the empirical evidence for this protocluster structure in the early universe, and the planned multi-wavelength follow-up observations of the brightest AzTEC sources towards 4C41.17 that may demonstrate that we are witnessing accelerated galaxy formation, via an increased rate of merging gas-rich galaxies within a rapidly-developing gravitational potential. AzTEC is one of the suite of instruments destined for the 50-m Large Millimeter Telescope (LMT). We will conclude this presentation with a summary of future LMT observations that will trace the evolution of obscured starformation in the dynamic environments towards a significant sample of intermediate and high-z powerful AGN with greater sensitivity and spatial resolution.

  11. Experimental evidence of space charge driven resonances in high intensity linear accelerators

    DOE PAGES

    Jeon, Dong -O

    2016-01-12

    In the construction of high intensity accelerators, it is the utmost goal to minimize the beam loss by avoiding or minimizing contributions of various halo formation mechanisms. As a halo formation mechanism, space charge driven resonances are well known for circular accelerators. However, the recent finding showed that even in linear accelerators the space charge potential can excite the 4σ = 360° fourth order resonance [D. Jeon et al., Phys. Rev. ST Accel. Beams 12, 054204 (2009)]. This study increased the interests in space charge driven resonances of linear accelerators. Experimental studies of the space charge driven resonances of highmore » intensity linear accelerators are rare as opposed to the multitude of simulation studies. This paper presents an experimental evidence of the space charge driven 4σ ¼ 360° resonance and the 2σ x(y) – 2σ z = 0 resonance of a high intensity linear accelerator through beam profile measurements from multiple wire-scanners. Moreover, measured beam profiles agree well with the characteristics of the space charge driven 4σ = 360° resonance and the 2σ x(y) – 2σ z = 0 resonance that are predicted by the simulation.« less

  12. Thrombosis Is Reduced by Inhibition of COX-1, but Unaffected by Inhibition of COX-2, in an Acute Model of Platelet Activation in the Mouse

    PubMed Central

    Armstrong, Paul C.; Kirkby, Nicholas S.; Zain, Zetty N.; Emerson, Michael; Mitchell, Jane A.; Warner, Timothy D.

    2011-01-01

    Background Clinical use of selective inhibitors of cyclooxygenase (COX)-2 appears associated with increased risk of thrombotic events. This is often hypothesised to reflect reduction in anti-thrombotic prostanoids, notably PGI2, formed by COX-2 present within endothelial cells. However, whether COX-2 is actually expressed to any significant extent within endothelial cells is controversial. Here we have tested the effects of acute inhibition of COX on platelet reactivity using a functional in vivo approach in mice. Methodology/Principal Findings A non-lethal model of platelet-driven thromboembolism in the mouse was used to assess the effects of aspirin (7 days orally as control) diclofenac (1 mg.kg−1, i.v.) and parecoxib (0.5 mg.kg−1, i.v.) on thrombus formation induced by collagen or the thromboxane (TX) A2-mimetic, U46619. The COX inhibitory profiles of the drugs were confirmed in mouse tissues ex vivo. Collagen and U46619 caused in vivo thrombus formation with the former, but not latter, sensitive to oral dosing with aspirin. Diclofenac inhibited COX-1 and COX-2 ex vivo and reduced thrombus formation in response to collagen, but not U46619. Parecoxib inhibited only COX-2 and had no effect upon thrombus formation caused by either agonist. Conclusions/Significance Inhibition of COX-1 by diclofenac or aspirin reduced thrombus formation induced by collagen, which is partly dependent upon platelet-derived TXA2, but not that induced by U46619, which is independent of platelet TXA2. These results are consistent with the model demonstrating the effects of COX-1 inhibition in platelets, but provide no support for the hypothesis that acute inhibition of COX-2 in the circulation increases thrombosis. PMID:21629780

  13. Ischemic Stroke: Histological Thrombus Composition and Pre-Interventional CT Attenuation Are Associated with Intervention Time and Rate of Secondary Embolism.

    PubMed

    Sporns, Peter B; Hanning, Uta; Schwindt, Wolfram; Velasco, Aglae; Buerke, Boris; Cnyrim, Christian; Minnerup, Jens; Heindel, Walter; Jeibmann, Astrid; Niederstadt, Thomas

    2017-01-01

    The introduction of stent retrievers has made the complete extraction and histological analysis of human thrombi possible. A number of large randomized trials have proven the efficacy of thrombectomy for ischemic stroke; however, thrombus composition could have an impact on the efficacy and risk of the intervention. We therefore investigated the impact of histologic thrombus features on interventional outcome and procedure-related embolisms. For a pre-interventional estimation of histologic features and outcome parameters, we assessed the pre-interventional CT attenuation of the thrombi. We prospectively included all consecutive patients with occlusion of the middle cerebral artery who underwent thrombectomy between December 2013 and February 2016 at our university medical center. Samples were histologically analyzed (H&E, Elastica van Gieson, Prussian blue); additionally, immunohistochemistry for CD3, CD20, and CD68/KiM1P was performed. Main thrombus components (fibrin, erythrocytes, and white blood cells) were determined and compared to intervention time, frequency of secondary embolisms, as well as additional clinical and interventional parameters. Additionally, we assessed the pre-interventional CT attenuation of the thrombi in relation to the unaffected side (rHU) and their association with histologic features. One hundred eighty patients were included; of these, in 168 patients (93.4%), complete recanalization was achieved and 27 patients (15%) showed secondary embolism in the control angiogram. We observed a significant association of high amounts of fibrin (p < 0.001), low percentage of red blood cells (p < 0.001), and lower rHU (p < 0.001) with secondary embolism. Higher rHU values were significantly associated with higher amounts of fibrin (p ≤ 0.001) and low percentage of red blood cells (p ≤ 0.001). Additionally, high amounts of fibrin were associated with longer intervention times (p ≤ 0.001), whereas thrombi with high amounts of

  14. Diesel engine exhaust accelerates plaque formation in a mouse model of Alzheimer's disease.

    PubMed

    Hullmann, Maja; Albrecht, Catrin; van Berlo, Damiën; Gerlofs-Nijland, Miriam E; Wahle, Tina; Boots, Agnes W; Krutmann, Jean; Cassee, Flemming R; Bayer, Thomas A; Schins, Roel P F

    2017-08-30

    Increasing evidence from toxicological and epidemiological studies indicates that the central nervous system is an important target for ambient air pollutants. We have investigated whether long-term inhalation exposure to diesel engine exhaust (DEE), a dominant contributor to particulate air pollution in urban environments, can aggravate Alzheimer's Disease (AD)-like effects in female 5X Familial AD (5XFAD) mice and their wild-type female littermates. Following 3 and 13 weeks exposures to diluted DEE (0.95 mg/m 3 , 6 h/day, 5 days/week) or clean air (controls) behaviour tests were performed and amyloid-β (Aβ) plaque formation, pulmonary histopathology and systemic inflammation were evaluated. In a string suspension task, assessing for grip strength and motor coordination, 13 weeks exposed 5XFAD mice performed significantly less than the 5XFAD controls. Spatial working memory deficits, assessed by Y-maze and X-maze tasks, were not observed in association with the DEE exposures. Brains of the 3 weeks DEE-exposed 5XFAD mice showed significantly higher cortical Aβ plaque load and higher whole brain homogenate Aβ42 levels than the clean air-exposed 5XFAD littermate controls. After the 13 weeks exposures, with increasing age and progression of the AD-phenotype of the 5XFAD mice, DEE-related differences in amyloid pathology were no longer present. Immunohistochemical evaluation of lungs of the mice revealed no obvious genetic background-related differences in tissue structure, and the DEE exposure did not cause histopathological changes in the mice of both backgrounds. Luminex analysis of plasma cytokines demonstrated absence of sustained systemic inflammation upon DEE exposure. Inhalation exposure to DEE causes accelerated plaque formation and motor function impairment in 5XFAD transgenic mice. Our study provides further support that the brain is a relevant target for the effects of inhaled DEE and suggests that long-term exposure to this ubiquitous air

  15. Progress In Plasma Accelerator Development for Dynamic Formation of Plasma Liners

    NASA Technical Reports Server (NTRS)

    Thio, Y. C. Francis; Eskridge, Richard; Martin, Adam; Smith, James; Lee, Michael; Cassibry, Jason T.; Griffin, Steven; Rodgers, Stephen L. (Technical Monitor)

    2002-01-01

    An experimental plasma accelerator for magnetic target fusion (MTF) applications under development at the NASA Marshall Space Flight Center is described. The accelerator is a coaxial pulsed plasma thruster (Figure 1). It has been tested experimentally and plasma jet velocities of approx.50 km/sec have been obtained. The plasma jet has been photographed with 10-ns exposure times to reveal a stable and repeatable plasma structure (Figure 2). Data for velocity profile information has been obtained using light pipes and magnetic probes embedded in the gun walls to record the plasma and current transit respectively at various barrel locations. Preliminary spatially resolved spectral data and magnetic field probe data are also presented. A high speed triggering system has been developed and tested as a means of reducing the gun "jitter". This jitter is being characterized and future work for second generation "ultra-low jitter" gun development is being identified.

  16. The effect of stochastic re-acceleration on the energy spectrum of shock-accelerated protons

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Afanasiev, Alexandr; Vainio, Rami; Kocharov, Leon

    2014-07-20

    The energy spectra of particles in gradual solar energetic particle (SEP) events do not always have a power-law form attributed to the diffusive shock acceleration mechanism. In particular, the observed spectra in major SEP events can take the form of a broken (double) power law. In this paper, we study the effect of a process that can modify the power-law spectral form produced by the diffusive shock acceleration: the stochastic re-acceleration of energetic protons by enhanced Alfvénic turbulence in the downstream region of a shock wave. There are arguments suggesting that this process can be important when the shock propagatesmore » in the corona. We consider a coronal magnetic loop traversed by a shock and perform Monte Carlo simulations of interactions of shock-accelerated protons with Alfvén waves in the loop. The wave-particle interactions are treated self-consistently, so the finiteness of the available turbulent energy is taken into account. The initial energy spectrum of particles is taken to be a power law. The simulations reveal that the stochastic re-acceleration leads either to the formation of a spectrum that is described in a wide energy range by a power law (although the resulting power-law index is different from the initial one) or to a broken power-law spectrum. The resulting spectral form is determined by the ratio of the energy density of shock-accelerated protons to the wave energy density in the shock's downstream region.« less

  17. Chinese expert consensus on multidisciplinary diagnosis and treatment of hepatocellular carcinoma with portal vein tumor thrombus: 2016 edition.

    PubMed

    Cheng, Shuqun; Chen, Minshan; Cai, Jianqiang

    2017-01-31

    Hepatocellular carcinoma is the fourth leading cause of cancer-related morbidity and mortality in China. Portal vein tumor thrombus (PVTT) is common and it worsens prognosis of hepatocellular carcinoma (HCC). There is no internationally accepted consensus or guideline for diagnosis and treatment of HCC with PVTT. Based on existing evidences and common current practices, Chinese Experts on Multidisciplinary Diagnosis and Treatment of HCC with portal vein tumor thrombus met to develop a national consensus on diagnosis and treatment of HCC with PVTT. The meeting concluded with the First Edition (version 2016) of consensus statements with grades of evidence given as grades Ia, Ib, IIa, IIb, III and IV, and ranking as Classes A, B, C, D and I for quality of evidence and strength of recommendation by the United State Preventive Service Task Force, respectively. The consensus suggests recommended treatment to be based on patients' PVTT type and ECOG functional status; surgery being the preferred treatment for Child-Pugh A, PVTT type I/II, and ECOG PS 0-1; transcatheter arterial chemoembolization (TACE) for non-resectable PVTT I/II and Child-Pugh A; and radiotherapy for non-resectable PVTT I/II/III and Child-Pugh A. Symptomatic treatment is recommended for Child-Pugh C, with massive ascites or gastrointestinal bleeding. By updating clinicians with treatment options for HCC with PVTT, the consensus statement aimed to prolong overall survival and to improve quality of life of patients with minimal treatment complication. Future treatment strategies for HCC with PVTT in China would depend on new evidences from more future clinical trials, especially studies defining the role of traditional Chinese medicine and clarifying molecular aspects of HCC.

  18. Pancreatic endocrine tumor with neoplastic venous thrombus and bilobar liver metastasis. A case report.

    PubMed

    Barbier, L; Turrini, O; Sarran, A; Delpero, J-R

    2010-02-01

    We report the case of an asymptomatic 56-year-old woman with a metastatic pancreatic endocrine tumor, fortuitously discovered by abdominal imaging. A CT-scan showed a large mass in the pancreatic tail invading the spleen and stomach; in addition, there was neoplastic thrombus within the spleno-mesentericoportal venous confluence and bilobar liver metastases. Surgical resection was performed in two stages. The first procedure was an extended left pancreatectomy with venous thrombectomy and "clearance" of the left hepatic lobe. During the interval, embolization of the right portal vein was carried out. Right hepatectomy and radiofrequency destruction of residual metastases was then performed. On the basis of completeness of the resection and the histopathological data, the patient did not undergo any adjuvant therapy, in accordance with French guidelines. At 1 year of follow-up, there was no evidence of recurrence. (c) 2010 Elsevier Masson SAS. All rights reserved.

  19. A critical role for both CD40 and VLA5 in angiotensin II-mediated thrombosis and inflammation.

    PubMed

    Senchenkova, Elena Y; Russell, Janice; Vital, Shantel A; Yildirim, Alper; Orr, A Wayne; Granger, D Neil; Gavins, Felicity N E

    2018-06-01

    Angiotensin II (Ang-II)-induced hypertension is associated with accelerated thrombus formation in arterioles and leukocyte recruitment in venules. The mechanisms that underlie the prothrombotic and proinflammatory responses to chronic Ang-II administration remain poorly understood. We evaluated the role of CD40/CD40 ligand (CD40L) signaling in Ang-II-mediated microvascular responses and assessed whether and how soluble CD40L (sCD40L) contributes to this response. Intravital video microscopy was performed to analyze leukocyte recruitment and dihydrorhodamine-123 oxidation in postcapillary venules. Thrombus formation in cremaster muscle arterioles was induced by using the light/dye endothelial cell injury model. Wild-type (WT), CD40 -/- , and CD40L -/- mice received Ang-II for 14 d via osmotic minipumps. Some mice were treated with either recombinant sCD40L or the VLA5 (very late antigen 5; α5β1) antagonist, ATN-161. Our results demonstrate that CD40 -/- , CD40L -/- , and WT mice that were treated with ATN-161 were protected against the thrombotic and inflammatory effects of Ang-II infusion. Infusion of sCD40L into CD40 -/- or CD40L -/- mice restored the prothrombotic effect of Ang-II infusion. Mice that were treated with ATN-161 and infused with sCD40L were protected against accelerated thrombosis. Collectively, these novel findings suggest that the mechanisms that underlie Ang-II-dependent thrombotic and inflammatory responses link to the signaling of CD40L via both CD40 and VLA5.-Senchenkova, E. Y., Russell, J., Vital, S. A., Yildirim, A., Orr, A. W., Granger, D. N., Gavins, F. N. E. A critical role for both CD40 and VLA5 in angiotensin II-mediated thrombosis and inflammation.

  20. Ultrasonic accelerates asparagine-glucose non-enzymatic browning reaction without acrylamide formation.

    PubMed

    Gao, Zhiqiang; Zheng, Junfeng; Chen, Lian

    2017-01-01

    Ultrasonic accelerated the asparagine-glucose non-enzymatic browning reaction with significant decrease of glucose and asparagine concentrations, and marked increase of intermediate products (UV-absorbance value at 294nm, Abs 294 ), melanoidins (UV-absorbance value at 420nm, Abs 420 ) and in vitro antioxidant activity (DPPH free radical scavenging activity). As the ultrasonic intensity was 17.83W/cm 2 , the asparagine-glucose solution's Abs 294 , Abs 420 and antioxidant activity increased from 0 to 1.26, 0.88 and 21.56%, respectively, and the glucose and asparagine concentrations of the asparagine-glucose solution reduced 58.97 and 12.57%, respectively. The high performance liquid chromatography (HPLC)-Diode Array Detector (DAD) analyses showed that no acrylamide was detected after 50-min ultrasonic reaction. This study suggested that ultrasonic at higher intensity was a potential method to accelerate the non-enzymatic browning reaction in the asparagine-glucose solution without acrylamide production. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Functional genomics in zebrafish permits rapid characterization of novel platelet membrane proteins

    PubMed Central

    O'Connor, Marie N.; Salles, Isabelle I.; Cvejic, Ana; Watkins, Nicholas A.; Walker, Adam; Garner, Stephen F.; Jones, Chris I.; Macaulay, Iain C.; Steward, Michael; Zwaginga, Jaap-Jan; Bray, Sarah L.; Dudbridge, Frank; de Bono, Bernard; Goodall, Alison H.; Stemple, Derek L.; Ouwehand, Willem H.

    2009-01-01

    In this study, we demonstrate the suitability of the vertebrate Danio rerio (zebrafish) for functional screening of novel platelet genes in vivo by reverse genetics. Comparative transcript analysis of platelets and their precursor cell, the megakaryocyte, together with nucleated blood cell elements, endothelial cells, and erythroblasts, identified novel platelet membrane proteins with hitherto unknown roles in thrombus formation. We determined the phenotype induced by antisense morpholino oligonucleotide (MO)–based knockdown of 5 of these genes in a laser-induced arterial thrombosis model. To validate the model, the genes for platelet glycoprotein (GP) IIb and the coagulation protein factor VIII were targeted. MO-injected fish showed normal thrombus initiation but severely impaired thrombus growth, consistent with the mouse knockout phenotypes, and concomitant knockdown of both resulted in spontaneous bleeding. Knockdown of 4 of the 5 novel platelet proteins altered arterial thrombosis, as demonstrated by modified kinetics of thrombus initiation and/or development. We identified a putative role for BAMBI and LRRC32 in promotion and DCBLD2 and ESAM in inhibition of thrombus formation. We conclude that phenotypic analysis of MO-injected zebrafish is a fast and powerful method for initial screening of novel platelet proteins for function in thrombosis. PMID:19109564

  2. Potent arterial antithrombotic effect of direct factor-Xa inhibition with ZK-807834 administered to coronary artery disease patients.

    PubMed

    Zafar, M Urooj; Farkouh, Michael E; Osende, Julio; Shimbo, Daichi; Palencia, Stella; Crook, Julia; Leadley, Robert; Fuster, Valentin; Chesebro, James H

    2007-03-01

    It was the objective of this study to evaluate the anti-thrombotic potency of direct factor-Xa inhibition with ZK-807834 in stable coronary patients, using an ex-vivo model of arterial thrombus formation. Tissue factor pathway is important in atherothrombosis. Direct factor-Xa blockade may more potently reduce thrombosis and prevent coronary events. Badimon Perfusion Chamber 5-minute quantitative studies have shown 40-55% arterial thrombus reduction with abciximab, 23% with clopidogrel, but none with heparin. Coronary patients (n = 18, 59 +/- 9 years, 55% males) were blindly randomized to four groups receiving 24-hour infusion of a low, medium or high dose of direct factor- Xa inhibitor ZK-807834, or placebo. Arterial thrombus formation was measured in Badimon Chamber at baseline, end-of-infusion [EoI], and four hours and eight hours after EoI, and factor-X activity, prothrombin time [PT] ratio and plasma drug levels were measured simultaneously. For the low-, medium- and high-dose ZK-807834 groups, mean percent-reduction in thrombus size from baseline to EoI were 29%, 34% and 68%, respectively (p < 0.001), and at 8-h post EoI were 11%, 19% and 27%, respectively (p < 0.01). Mean PT-ratio prolongation showed a strong linear relationship (Pearson's r = 0.93) with ZK-807834 plasma concentration. Mean percent-reduction in factor-X activity from baseline was 13%, 42% and 58%, respectively. Placebo had no effect on thrombus size or factor-X activity. In conclusion, direct factor-Xa inhibition with ZK-807834 markedly reduces ex-vivo arterial thrombus formation and factor-X activity in a dose-dependent manner. Plasma levels of ZK-807834 show a strong linear correlation with PT ratio. This direct factor-Xa inhibitor may reduce the need for additional potent glycoprotein IIbIIIa inhibition.

  3. Zinc oxide nanoparticles induce migration and adhesion of monocytes to endothelial cells and accelerate foam cell formation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Suzuki, Yuka; Tada-Oikawa, Saeko; Ichihara, Gaku

    Metal oxide nanoparticles are widely used in industry, cosmetics, and biomedicine. However, the effects of exposure to these nanoparticles on the cardiovascular system remain unknown. The present study investigated the effects of nanosized TiO{sub 2} and ZnO particles on the migration and adhesion of monocytes, which are essential processes in atherosclerogenesis, using an in vitro set-up of human umbilical vein endothelial cells (HUVECs) and human monocytic leukemia cells (THP-1). We also examined the effects of exposure to nanosized metal oxide particles on macrophage cholesterol uptake and foam cell formation. The 16-hour exposure to ZnO particles increased the level of monocytemore » chemotactic protein-1 (MCP-1) and induced the migration of THP-1 monocyte mediated by increased MCP-1. Exposure to ZnO particles also induced adhesion of THP-1 cells to HUVECs. Moreover, exposure to ZnO particles, but not TiO{sub 2} particles, upregulated the expression of membrane scavenger receptors of modified LDL and increased cholesterol uptake in THP-1 monocytes/macrophages. In the present study, we found that exposure to ZnO particles increased macrophage cholesterol uptake, which was mediated by an upregulation of membrane scavenger receptors of modified LDL. These results suggest that nanosized ZnO particles could potentially enhance atherosclerogenesis and accelerate foam cell formation. - Highlights: • Effects of metal oxide nanoparticles on foam cell formation were investigated. • Exposure to ZnO nanoparticles induced migration and adhesion of monocytes. • Exposure to ZnO nanoparticles increased macrophage cholesterol uptake. • Expression of membrane scavenger receptors of modified LDL was also increased. • These effects were not observed after exposure to TiO{sub 2} nanoparticles.« less

  4. Naked singularities as particle accelerators

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Patil, Mandar; Joshi, Pankaj S.

    We investigate here the particle acceleration by naked singularities to arbitrarily high center of mass energies. Recently it has been suggested that black holes could be used as particle accelerators to probe the Planck scale physics. We show that the naked singularities serve the same purpose and probably would do better than their black hole counterparts. We focus on the scenario of a self-similar gravitational collapse starting from a regular initial data, leading to the formation of a globally naked singularity. It is seen that when particles moving along timelike geodesics interact and collide near the Cauchy horizon, the energymore » of collision in the center of mass frame will be arbitrarily high, thus offering a window to Planck scale physics.« less

  5. Accelerated Threshold Fatigue Crack Growth Effect-Powder Metallurgy Aluminum Alloy

    NASA Technical Reports Server (NTRS)

    Piascik, R. S.; Newman, J. A.

    2002-01-01

    Fatigue crack growth (FCG) research conducted in the near threshold regime has identified a room temperature creep crack growth damage mechanism for a fine grain powder metallurgy (PM) aluminum alloy (8009). At very low (Delta) K, an abrupt acceleration in room temperature FCG rate occurs at high stress ratio (R = K(sub min)/K(sub max)). The near threshold accelerated FCG rates are exacerbated by increased levels of K(sub max) (K(sub max) = 0.4 K(sub IC)). Detailed fractographic analysis correlates accelerated FCG with the formation of crack-tip process zone micro-void damage. Experimental results show that the near threshold and K(sub max) influenced accelerated crack growth is time and temperature dependent.

  6. AngioVac Aspiration for Paradoxical Emboli Protection through a Fenestrated Fontan During Central Venous Thrombus Manipulation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Al-Hakim, Ramsey, E-mail: ralhakim@mednet.ucla.edu; Patel, Komal, E-mail: kdpatel@mednet.ucla.edu; Moriarty, John M., E-mail: jmoriarty@mednet.ucla.edu

    2015-06-15

    This case reports describes a 39-year-old female with a history of surgically repaired hypoplastic left heart syndrome who presented with a left peripherally inserted central catheter (PICC) with associated large volume subclavian and brachiocephalic vein thrombus. Due to the presence of a right-to-left shunt via a fenestrated Fontan, there was clinical concern for a paradoxical embolism during removal of the PICC. The AngioVac aspiration system was successfully utilized to aspirate thromboemboli from the level of the proximal Glenn shunt during manipulation and removal of the PICC. This is the first reported case to demonstrate the safe and effective use ofmore » the AngioVac aspiration system for protection of paradoxical emboli through a cardiac right-to-left shunt during a procedure at high risk for thromboembolism.« less

  7. AngioVac Aspiration for Paradoxical Emboli Protection through a Fenestrated Fontan During Central Venous Thrombus Manipulation.

    PubMed

    Al-Hakim, Ramsey; Patel, Komal; Moriarty, John M

    2015-06-01

    This case reports describes a 39-year-old female with a history of surgically repaired hypoplastic left heart syndrome who presented with a left peripherally inserted central catheter (PICC) with associated large volume subclavian and brachiocephalic vein thrombus. Due to the presence of a right-to-left shunt via a fenestrated Fontan, there was clinical concern for a paradoxical embolism during removal of the PICC. The AngioVac aspiration system was successfully utilized to aspirate thromboemboli from the level of the proximal Glenn shunt during manipulation and removal of the PICC. This is the first reported case to demonstrate the safe and effective use of the AngioVac aspiration system for protection of paradoxical emboli through a cardiac right-to-left shunt during a procedure at high risk for thromboembolism.

  8. The Student Course Experience among Online, Accelerated, and Traditional Courses

    ERIC Educational Resources Information Center

    Bielitz, Colleen L.

    2016-01-01

    The demand by the public for a wider variety of course formats has led to complexity in determining a course's optimal delivery format as many faculty members still believe that online and accelerated courses do not offer students an equivalent experience to traditional face to face instruction. The purpose of this quantitative, comparative study…

  9. Acceleration modules in linear induction accelerators

    NASA Astrophysics Data System (ADS)

    Wang, Shao-Heng; Deng, Jian-Jun

    2014-05-01

    The Linear Induction Accelerator (LIA) is a unique type of accelerator that is capable of accelerating kilo-Ampere charged particle current to tens of MeV energy. The present development of LIA in MHz bursting mode and the successful application into a synchrotron have broadened LIA's usage scope. Although the transformer model is widely used to explain the acceleration mechanism of LIAs, it is not appropriate to consider the induction electric field as the field which accelerates charged particles for many modern LIAs. We have examined the transition of the magnetic cores' functions during the LIA acceleration modules' evolution, distinguished transformer type and transmission line type LIA acceleration modules, and re-considered several related issues based on transmission line type LIA acceleration module. This clarified understanding should help in the further development and design of LIA acceleration modules.

  10. A systematic FPGA acceleration design for applications based on convolutional neural networks

    NASA Astrophysics Data System (ADS)

    Dong, Hao; Jiang, Li; Li, Tianjian; Liang, Xiaoyao

    2018-04-01

    Most FPGA accelerators for convolutional neural network are designed to optimize the inner acceleration and are ignored of the optimization for the data path between the inner accelerator and the outer system. This could lead to poor performance in applications like real time video object detection. We propose a brand new systematic FPFA acceleration design to solve this problem. This design takes the data path optimization between the inner accelerator and the outer system into consideration and optimizes the data path using techniques like hardware format transformation, frame compression. It also takes fixed-point, new pipeline technique to optimize the inner accelerator. All these make the final system's performance very good, reaching about 10 times the performance comparing with the original system.

  11. Accelerating anodic biofilms formation and electron transfer in microbial fuel cells: Role of anionic biosurfactants and mechanism.

    PubMed

    Zhang, Yunshu; Jiang, Junqiu; Zhao, Qingliang; Gao, YunZhi; Wang, Kun; Ding, Jing; Yu, Hang; Yao, Yue

    2017-10-01

    Anodic electron transfer is the predominant electricity generation process of MFCs. To accelerate anodic biofilms formation and electron transfer, 40mg/L, 80mg/L, and 120mg/L of rhamnolipid biosurfactants were added to the anolyte, resulting in an increased abiotic capacitance from 15.12F/m 2 (control) to 16.54F/m 2 , 18.00F/m 2 , and 19.39F/m 2 , respectively. Anodic biofilm formation was facilitated after dosing 40mg/L of rhamnolipids on the 7th day after inoculation, resulting in an increased anodic biofilm coverage from 0.43% to 42.51%, and an increased maximum power density from 6.92±1.18W/m 3 to 9.93±0.88W/m 3 . Furthermore, the adsorption of rhamnolipids on the anode caused the Frumkin effect, leading to a decrease of equilibrium potential from -0.43V to -0.56V, and an increase of exchange current density from 5.09×10 -3 A/m 2 to 8.72×10 -3 A/m 2 . However, electron transfer was blocked when the rhamnolipid concentration was further increased to 80mg/L, and 120mg/L. Analysis of the anodic bacterial communities revealed that rhamnolipids facilitated the enrichment of exoelectrogen, increasing the total proportion from 65% to 81%. Additionally, biosurfactants were found to have significant impacts on the composition of exoelectrogens. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Cavitation onset caused by acceleration

    PubMed Central

    Pan, Zhao; Kiyama, Akihito; Tagawa, Yoshiyuki; Daily, David J.; Thomson, Scott L.; Hurd, Randy

    2017-01-01

    Striking the top of a liquid-filled bottle can shatter the bottom. An intuitive interpretation of this event might label an impulsive force as the culprit in this fracturing phenomenon. However, high-speed photography reveals the formation and collapse of tiny bubbles near the bottom before fracture. This observation indicates that the damaging phenomenon of cavitation is at fault. Cavitation is well known for causing damage in various applications including pipes and ship propellers, making accurate prediction of cavitation onset vital in several industries. However, the conventional cavitation number as a function of velocity incorrectly predicts the cavitation onset caused by acceleration. This unexplained discrepancy leads to the derivation of an alternative dimensionless term from the equation of motion, predicting cavitation as a function of acceleration and fluid depth rather than velocity. Two independent research groups in different countries have tested this theory; separate series of experiments confirm that an alternative cavitation number, presented in this paper, defines the universal criteria for the onset of acceleration-induced cavitation. PMID:28739956

  13. Cavitation onset caused by acceleration.

    PubMed

    Pan, Zhao; Kiyama, Akihito; Tagawa, Yoshiyuki; Daily, David J; Thomson, Scott L; Hurd, Randy; Truscott, Tadd T

    2017-07-24

    Striking the top of a liquid-filled bottle can shatter the bottom. An intuitive interpretation of this event might label an impulsive force as the culprit in this fracturing phenomenon. However, high-speed photography reveals the formation and collapse of tiny bubbles near the bottom before fracture. This observation indicates that the damaging phenomenon of cavitation is at fault. Cavitation is well known for causing damage in various applications including pipes and ship propellers, making accurate prediction of cavitation onset vital in several industries. However, the conventional cavitation number as a function of velocity incorrectly predicts the cavitation onset caused by acceleration. This unexplained discrepancy leads to the derivation of an alternative dimensionless term from the equation of motion, predicting cavitation as a function of acceleration and fluid depth rather than velocity. Two independent research groups in different countries have tested this theory; separate series of experiments confirm that an alternative cavitation number, presented in this paper, defines the universal criteria for the onset of acceleration-induced cavitation.

  14. Cavitation onset caused by acceleration

    NASA Astrophysics Data System (ADS)

    Pan, Zhao; Kiyama, Akihito; Tagawa, Yoshiyuki; Daily, David J.; Thomson, Scott L.; Hurd, Randy; Truscott, Tadd T.

    2017-08-01

    Striking the top of a liquid-filled bottle can shatter the bottom. An intuitive interpretation of this event might label an impulsive force as the culprit in this fracturing phenomenon. However, high-speed photography reveals the formation and collapse of tiny bubbles near the bottom before fracture. This observation indicates that the damaging phenomenon of cavitation is at fault. Cavitation is well known for causing damage in various applications including pipes and ship propellers, making accurate prediction of cavitation onset vital in several industries. However, the conventional cavitation number as a function of velocity incorrectly predicts the cavitation onset caused by acceleration. This unexplained discrepancy leads to the derivation of an alternative dimensionless term from the equation of motion, predicting cavitation as a function of acceleration and fluid depth rather than velocity. Two independent research groups in different countries have tested this theory; separate series of experiments confirm that an alternative cavitation number, presented in this paper, defines the universal criteria for the onset of acceleration-induced cavitation.

  15. Formation Flying in Earth, Libration, and Distant Retrograde Orbits

    NASA Technical Reports Server (NTRS)

    Folta, David C.

    2004-01-01

    This slide presentation examines the current and future state of formation flying, LEO formations, control strategies for flight in the vicinity of the libration points, and distant retrograde orbit formations. This discussion of LEO formations includes background on perturbation theory/accelerations and LEO formation flying. The discussion of strategies for formation flight in the vicinity of the libration points includes libration missions and natural and controlled libration orbit formations. A reference list is included.

  16. Compact torus accelerator as a driver for ICF

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tobin, M.T.; Meier, W.R.; Morse, E.C.

    1986-01-01

    The authors have carried out further investigations of the technical issues associated with using a compact torus (CT) accelerator as a driver for inertial confinement fusion (ICF). In a CT accelerator, a magnetically confined, torus-shaped plasma is compressed, accelerated, and focused by two concentric electrodes. After its initial formation, the torus shape is maintained for lifetimes exceeding 1 ms by inherent poloidal and toroidal currents. Hartman suggests acceleration and focusing of such a plasma ring will not cause dissolution within certain constraints. In this study, we evaluated a point design based on an available capacitor bank energy of 9.2 MJ.more » This accelerator, which was modeled by a zero-dimensional code, produces a xenon plasma ring with a 0.73-cm radius, a velocity of 4.14 x 10/sup 9/ cm/s, and a mass of 4.42 ..mu..g. The energy of the plasma ring as it leaves the accelerator is 3.8 MJ, or 41% of the capacitor bank energy. Our studies confirm the feasibility of producing a plasma ring with the characteristics required to induce fusion in an ICF target with a gain greater than 50. The low cost and high efficiency of the CT accelerator are particularly attractive. Uncertainties concerning propagation, accelerator lifetime, and power supply must be resolved to establish the viability of the accelerator as an ICF driver.« less

  17. Plasma Accelerator Development for Dynamic Formation of Plasma Liners: A Status Report

    NASA Technical Reports Server (NTRS)

    Thio, Y. C. Francis; Eskridge, Richard; Martin, Adam; Smith, James; Lee, Michael; Rodgers, Stephen L. (Technical Monitor)

    2001-01-01

    An experimental plasma accelerator for magnetic target fusion (MTF) applications under development at the NASA Marshall Space Flight Center is described. The accelerator is a pulsed plasma thruster and has been tested experimentally and plasma jet velocities of approximately 50 km/sec have been obtained. The plasma jet structure has been photographed with 10 ns exposure times to reveal a stable and repeatable plasma structure. Data for velocity profile information has been obtained using light pipes embedded in the gun walls to record the plasma transit at various barrel locations. Preliminary spatially resolved spectral data and magnetic field probe data are also presented. A high speed triggering system has been developed and tested as a means of reducing the gun "jitter". This jitter is being characterized and future work for second generation "ultra-low jitter" gun development is being identified.

  18. Accelerated degradation of silicon metallization systems

    NASA Technical Reports Server (NTRS)

    Lathrop, J. W.

    1983-01-01

    Clemson University has been engaged for the past five years in a program to determine the reliability attributes of solar cells by means of accelerated test procedures. The cells are electrically measured and visually inspected and then subjected for a period of time to stress in excess of that normally encountered in use, and then they are reinspected. Changes are noted and the process repeated. This testing has thus far involved 23 different unencapsulated cell types from 12 different manufacturers, and 10 different encapsulated cell types from 9 different manufacturers. Reliability attributes of metallization systems can be classified as major or minor, depending on the severity of the effects observed. As a result of the accelerated testing conducted under the Clemson program, major effects have been observed related to contact resistance and to mechanical adherence and solderability. This paper does not attempt a generalized survey of accelerated test results, but rather concentrates on one particular attribute of metallization that has been observed to cause electrical degradation - increased contact resistance due to Schottky barrier formation. In this example basic semiconductor theory was able to provide an understanding of the electrical effects observed during accelerated stress testing.

  19. Tracing accelerated galaxy formation in a proto-cluster at z=3.8 with GMOS

    NASA Astrophysics Data System (ADS)

    Handel Hughes, David; Lowenthal, James; Wilson, Grant; Yun, Min S.; Fazio, Giovanni G.; Huang, Jiasheng; Aretxaga, Itziar; Porras, Alicia; Smail, Ian; Ivison, Rob J.; Stevens, Jason; Dunlop, James S.

    2007-08-01

    The 1.1mm AzTEC camera has recently conducted the largest and most sensitive survey at mm-wavelengths towards a powerful high-redshift radio galaxy: 4C41.17 at z 3.8. The 1.1mm map reveals a significant over-density of luminous, massive dust-enshrouded galaxies, a factor of 10 more numerous than the blank-field mm-galaxy population, which statistically is expected to lie at lower-redshifts, z 2.2. The AzTEC sources are expected to trace the bulk of the elliptical galaxy formation within a massive protocluster at z 3.8, over an unprecedentedly large area of 6 x 6 Mpc^2. We propose to acquire multi-object spectroscopic observations over 3 adjacent GMOS fields to provide redshifts for 5 SMA/AzTEC sources, which have sub-arcsec interferometric precisions, identifying unambiguously their optical/IR counterparts, which are inferred to be forming stars at rates in excess of 500 M_sun/yr ( L(FIR) > 10^13 L_sun ). Although these are dusty objects, we expect most of them to have patchy obscuration, and thus be able to detect emission-lines from the star-forming regions, as has been achieved with the mm-selected blank-field population. Additional slitlets in the 3 GMOS masks will also simultaneously measure the redshift of 30 neighbouring (< 20") optical/Spitzer selected galaxies that could be associated with the haloes of these SMA detected AzTEC sources, and 60 additional optical/Spitzer sources that, through photo-z, are likely to be at z 3.8 and be associated with other mm-galaxies that lie within the AzTEC map. These GMOS data will identify whether small groups of dynamically-interacting galaxies in the local environment (dark matter haloes) of the gas-rich, luminous starburst AzTEC sources are stimulating the accelerated levels of galaxy formation observed towards this biased region (protocluster) in the early Universe.

  20. Current Fragmentation and Particle Acceleration in Solar Flares

    NASA Astrophysics Data System (ADS)

    Cargill, P. J.; Vlahos, L.; Baumann, G.; Drake, J. F.; Nordlund, Å.

    2012-11-01

    Particle acceleration in solar flares remains an outstanding problem in plasma physics and space science. While the observed particle energies and timescales can perhaps be understood in terms of acceleration at a simple current sheet or turbulence site, the vast number of accelerated particles, and the fraction of flare energy in them, defies any simple explanation. The nature of energy storage and dissipation in the global coronal magnetic field is essential for understanding flare acceleration. Scenarios where the coronal field is stressed by complex photospheric motions lead to the formation of multiple current sheets, rather than the single monolithic current sheet proposed by some. The currents sheets in turn can fragment into multiple, smaller dissipation sites. MHD, kinetic and cellular automata models are used to demonstrate this feature. Particle acceleration in this environment thus involves interaction with many distributed accelerators. A series of examples demonstrate how acceleration works in such an environment. As required, acceleration is fast, and relativistic energies are readily attained. It is also shown that accelerated particles do indeed interact with multiple acceleration sites. Test particle models also demonstrate that a large number of particles can be accelerated, with a significant fraction of the flare energy associated with them. However, in the absence of feedback, and with limited numerical resolution, these results need to be viewed with caution. Particle in cell models can incorporate feedback and in one scenario suggest that acceleration can be limited by the energetic particles reaching the condition for firehose marginal stability. Contemporary issues such as footpoint particle acceleration are also discussed. It is also noted that the idea of a "standard flare model" is ill-conceived when the entire distribution of flare energies is considered.

  1. Preliminary Study for Measurement of Shear Stress and Hemocompatibility Using Commercialized Lab on a Chip.

    PubMed

    Lee, Joshua; Kim, In Gi; Oh, Young Min; Park, Chan-Hee; Kim, Cheol Sang

    2018-02-01

    We have investigated the effect of flow rate on shear stress and in turn thrombus formation on a lab-on-a-chip with a microchannel that is suitable for cell culture and growth. Using a combination of Arduino UNO, Arduino Motor Shield, and a SERVO stepper motor, we created a pump system that closely mimics the in vivo conditions of the human body. With this system, we achieved continuous flow of blood and observed attached platelets at the bottom of the collagen coated microslide, confirming that with shear stress, thrombus formation increases.

  2. A New Paradigm for Flare Particle Acceleration

    NASA Astrophysics Data System (ADS)

    Guidoni, Silvina E.; Karpen, Judith T.; DeVore, C. Richard

    2017-08-01

    The mechanism that accelerates particles to the energies required to produce the observed high-energy impulsive emission and its spectra in solar flares is not well understood. Here, we propose a first-principle-based model of particle acceleration that produces energy spectra that closely resemble those derived from hard X-ray observations. Our mechanism uses contracting magnetic islands formed during fast reconnection in solar flares to accelerate electrons, as first proposed by Drake et al. (2006) for kinetic-scale plasmoids. We apply these ideas to MHD-scale islands formed during fast reconnection in a simulated eruptive flare. A simple analytic model based on the particles’ adiabatic invariants is used to calculate the energy gain of particles orbiting field lines in our ultrahigh-resolution, 2.5D, MHD numerical simulation of a solar eruption (flare + coronal mass ejection). Then, we analytically model electrons visiting multiple contracting islands to account for the observed high-energy flare emission. Our acceleration mechanism inherently produces sporadic emission because island formation is intermittent. Moreover, a large number of particles could be accelerated in each macroscopic island, which may explain the inferred rates of energetic-electron production in flares. We conclude that island contraction in the flare current sheet is a promising candidate for electron acceleration in solar eruptions. This work was supported in part by the NASA LWS and H-SR programs..

  3. Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy

    PubMed Central

    Angelillo-Scherrer, Anne; Burnier, Laurent; Flores, Nathalie; Savi, Pierre; DeMol, Maria; Schaeffer, Paul; Herbert, Jean-Marc; Lemke, Greg; Goff, Stephen P.; Matsushima, Glenn K.; Earp, H. Shelton; Vesin, Christian; Hoylaerts, Marc F.; Plaisance, Stéphane; Collen, Désiré; Conway, Edward M.; Wehrle-Haller, Bernhard; Carmeliet, Peter

    2005-01-01

    Mechanisms regulating thrombus stabilization remain largely unknown. Here, we report that loss of any 1 of the Gas6 receptors (Gas6-Rs), i.e., Tyro3, Axl, or Mer, or delivery of a soluble extracellular domain of Axl that traps Gas6 protects mice against life-threatening thrombosis. Loss of a Gas6-R does not prevent initial platelet aggregation but impairs subsequent stabilization of platelet aggregates, at least in part by reducing “outside-in” signaling and platelet granule secretion. Gas6, through its receptors, activates PI3K and Akt and stimulates tyrosine phosphorylation of the β3 integrin, thereby amplifying outside-in signaling via αIIbβ3. Blocking the Gas6-R–αIIbβ3 integrin cross-talk might be a novel approach to the reduction of thrombosis. PMID:15650770

  4. Design of a Microwave Assisted Discharge Inductive Plasma Accelerator

    NASA Technical Reports Server (NTRS)

    Hallock, Ashley K.; Polzin, Kurt A.

    2010-01-01

    The design and construction of a thruster that employs electrodeless plasma preionization and pulsed inductive acceleration is described. Preionization is achieved through an electron cyclotron resonance discharge that produces a weakly-ionized plasma at the face of a conical theta pinch-shaped inductive coil. The presence of the preionized plasma allows for current sheet formation at lower discharge voltages than those employed in other pulsed inductive accelerators that do not employ preionization. The location of the electron cyclotron resonance discharge is controlled through the design of the applied magnetic field in the thruster. Finite element analysis shows that there is an arrangement of permanent magnets that yields a small volume of resonant magnetic field at the coil face. Preionization in the resonant zone leads to current sheet formation at the coil face, which minimizes the initial inductance of the pulse circuit and maximizes the potential electrical efficiency of the accelerator. A magnet assembly was constructed around an inductive coil to provide structural support to the selected arrangement of neodymium magnets. Measured values of the resulting magnetic field compare favorably with the finite element model.

  5. Novel microspheres reduce the formation of deep venous thrombosis and repair the vascular wall in a rat model.

    PubMed

    Dai, Bingyang; Li, Lan; Li, Qiangqiang; Song, Xiaoxiao; Chen, Dongyang; Dai, Jin; Yao, Yao; Yan, Wenjin; Teng, Huajian; Yang, Fang; Xu, Zhihong; Jiang, Qing

    2017-07-01

    : L-Arginine (L-arg), widely known as a substrate for endogenous nitric oxide synthesis, can improve endothelial function associated with the vasculature, inhibit platelet aggregation, and alter the activity of vascular smooth muscle cells. P-selectin is a membrane component of the platelet alpha-granule and the endothelial cell-specific Wiebel-Palade body that plays a central role in mediating interactions between platelets and both leukocytes and the endothelium. The experiment was designed to evaluate the effect of novel microspheres with L-arg targeting P-selectin on the formation of deep vein thrombosis and repair of vascular wall in a rat model. Thrombosis of the inferior vena cava was induced by applying a piece of filter paper (5 mm × 10 mm) saturated with 10% FeCl3 solution for 5 min. Targeted microspheres with L-arg, targeted microspheres with water, and saline were injected into the tail veins of the rats after 30 min of applying the filter paper saturated with 10% FeCl3 solution. The dry weight and length of the thrombus isolated from the inferior vena cava were significantly decreased in the group with L-arg in microsphere after 24 h. No significant differences in prothrombin time, activated partial thromboplastin time, thrombin time, and fibrinogen among the groups were indicated. Images revealed that apoptosis in the vascular wall was less in the group injected with targeted microspheres with L-arg than in the other two groups at 1 and 8 d postsurgery. Meanwhile, cell proliferation was considerably excessive in the group injected with L-arg wrapped in targeted microspheres. Therefore, these novel microspheres could decrease the formation of thrombus in the early stages and in the subsequent periods of thrombosis. The microspheres can also enhance the vitality of impaired endothelial cells and reduce cell apoptosis.

  6. Novel microspheres reduce the formation of deep venous thrombosis and repair the vascular wall in a rat model

    PubMed Central

    Dai, Bingyang; Li, Lan; Li, Qiangqiang; Song, Xiaoxiao; Chen, Dongyang; Dai, Jin; Yao, Yao; Yan, Wenjin; Teng, Huajian; Yang, Fang; Xu, Zhihong; Jiang, Qing

    2017-01-01

    L-Arginine (L-arg), widely known as a substrate for endogenous nitric oxide synthesis, can improve endothelial function associated with the vasculature, inhibit platelet aggregation, and alter the activity of vascular smooth muscle cells. P-selectin is a membrane component of the platelet alpha-granule and the endothelial cell-specific Wiebel–Palade body that plays a central role in mediating interactions between platelets and both leukocytes and the endothelium. The experiment was designed to evaluate the effect of novel microspheres with L-arg targeting P-selectin on the formation of deep vein thrombosis and repair of vascular wall in a rat model. Thrombosis of the inferior vena cava was induced by applying a piece of filter paper (5 mm × 10 mm) saturated with 10% FeCl3 solution for 5 min. Targeted microspheres with L-arg, targeted microspheres with water, and saline were injected into the tail veins of the rats after 30 min of applying the filter paper saturated with 10% FeCl3 solution. The dry weight and length of the thrombus isolated from the inferior vena cava were significantly decreased in the group with L-arg in microsphere after 24 h. No significant differences in prothrombin time, activated partial thromboplastin time, thrombin time, and fibrinogen among the groups were indicated. Images revealed that apoptosis in the vascular wall was less in the group injected with targeted microspheres with L-arg than in the other two groups at 1 and 8 d postsurgery. Meanwhile, cell proliferation was considerably excessive in the group injected with L-arg wrapped in targeted microspheres. Therefore, these novel microspheres could decrease the formation of thrombus in the early stages and in the subsequent periods of thrombosis. The microspheres can also enhance the vitality of impaired endothelial cells and reduce cell apoptosis. PMID:28306627

  7. Stable quasi-monoenergetic ion acceleration from the laser-driven shocks in a collisional plasma

    NASA Astrophysics Data System (ADS)

    Bhadoria, Shikha; Kumar, Naveen; Keitel, Christoph H.

    2017-10-01

    Effect of collisions on the shock formation and subsequent ion acceleration from the laser-plasma interaction is explored by the means of particle-in-cell simulations. In this setup, the incident laser pushes the laser-plasma interface inside the plasma target through the hole-boring effect and generates hot electrons. The propagation of these hot electrons inside the target excites a return plasma current, leading to filamentary structures caused by the Weibel/filamentation instability. Weakening of the space-charge effects due to collisions results in the shock formation with a higher density jump than in a collisionless plasma. This results in the formation of a stronger shock leading to a stable quasi-monoenergetic acceleration of ions.

  8. Possible benefits of catheters with lateral holes in coronary thrombus aspiration: a computational study for different clot viscosities and vacuum pressures.

    PubMed

    Soleimani, Sajjad; Dubini, Gabriele; Pennati, Giancarlo

    2014-10-01

    According to a number of clinical studies, coronary aspiration catheters are useful tools to remove a thrombus (blood clot) blocking a coronary artery. However, these thrombectomy devices may fail to remove the blood clot entirely. Few studies have been devoted to a systematic analysis of factors affecting clot aspiration. The geometric characteristics of the aspiration catheter, the physical properties of the thrombus, and the applied vacuum pressure are crucial parameters. In this study, the aspiration of a blood clot blocking a coronary bifurcation is computationally simulated. The clot is modeled as a highly viscous fluid, and a two-phase (blood and clot) problem is solved. The effects of geometric variations in the tip of the coronary catheter, including lateral hole size and location, are investigated considering different aspiration pressures and clot viscosities. A Bird-Carreau model is adopted for blood viscosity, while a power law model is used to describe the clot rheology. Computational results for blood clot aspiration show that the presence of holes in the lateral part of the tip of the catheter can be beneficial depending on clot viscosity, hole features, and applied aspiration pressure. In general, the holes are beneficial when the clot viscosity is low, while aspiration catheters without any extra lateral holes exhibit better performance for higher clot viscosity. However, when higher aspiration pressures are applied, the catheters tend to behave relatively similarly in removing clots with various viscosities, reducing the role of the clot viscosity. Copyright © 2014 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  9. Accelerator system and method of accelerating particles

    NASA Technical Reports Server (NTRS)

    Wirz, Richard E. (Inventor)

    2010-01-01

    An accelerator system and method that utilize dust as the primary mass flux for generating thrust are provided. The accelerator system can include an accelerator capable of operating in a self-neutralizing mode and having a discharge chamber and at least one ionizer capable of charging dust particles. The system can also include a dust particle feeder that is capable of introducing the dust particles into the accelerator. By applying a pulsed positive and negative charge voltage to the accelerator, the charged dust particles can be accelerated thereby generating thrust and neutralizing the accelerator system.

  10. Ponderomotive Acceleration in Coronal Loops

    NASA Astrophysics Data System (ADS)

    Dahlburg, Russell B.; Laming, J. Martin; Taylor, Brian; Obenschain, Keith

    2017-08-01

    Ponderomotive acceleration has been asserted to be a cause of the First Ionization Potential (FIP) effect, the by now well known enhancement in abundance by a factor of 3-4 over photospheric values of elements in the solar corona with FIP less than about 10 eV. It is shown here by means of numerical simulations that ponderomotive acceleration occurs in solar coronal loops, with the appropriate magnitude and direction, as a ``byproduct'' of coronal heating. The numerical simulations are performed with the HYPERION code, which solves the fully compressible three-dimensional magnetohydrodynamic equations including nonlinear thermal conduction and optically thin radiation. Numerical simulations of a coronal loops with an axial magnetic field from 0.005 Teslas to 0.02 Teslas and lengths from 25000 km to 75000 km are presented. In the simulations the footpoints of the axial loop magnetic field are convected by random, large-scale motions. There is a continuous formation and dissipation of field-aligned current sheets which act to heat the loop. As a consequence of coronal magnetic reconnection, small scale, high speed jets form. The familiar vortex quadrupoles form at reconnection sites. Between the magnetic footpoints and the corona the reconnection flow merges with the boundary flow. It is in this region that the ponderomotive acceleration occurs. Mirroring the character of the coronal reconnection, the ponderomotive acceleration is also found to be intermittent.

  11. The kunitz protease inhibitor domain of protease nexin-2 inhibits factor XIa and murine carotid artery and middle cerebral artery thrombosis

    PubMed Central

    Wu, Wenman; Li, Hongbo; Navaneetham, Duraiswamy; Reichenbach, Zachary W.; Tuma, Ronald F.

    2012-01-01

    Coagulation factor XI (FXI) plays an important part in both venous and arterial thrombosis, rendering FXIa a potential target for the development of antithrombotic therapy. The kunitz protease inhibitor (KPI) domain of protease nexin-2 (PN2) is a potent, highly specific inhibitor of FXIa, suggesting its possible role in the inhibition of FXI-dependent thrombosis in vivo. Therefore, we examined the effect of PN2KPI on thrombosis in the murine carotid artery and the middle cerebral artery. Intravenous administration of PN2KPI prolonged the clotting time of both human and murine plasma, and PN2KPI inhibited FXIa activity in both human and murine plasma in vitro. The intravenous administration of PN2KPI into WT mice dramatically decreased the progress of FeCl3-induced thrombus formation in the carotid artery. After a similar initial rate of thrombus formation with and without PN2KPI treatment, the propagation of thrombus formation after 10 minutes and the amount of thrombus formed were significantly decreased in mice treated with PN2KPI injection compared with untreated mice. In the middle cerebral artery occlusion model, the volume and fraction of ischemic brain tissue were significantly decreased in PN2KPI-treated compared with untreated mice. Thus, inhibition of FXIa by PN2KPI is a promising approach to antithrombotic therapy. PMID:22674803

  12. Thioredoxin Inhibitors Attenuate Platelet Function and Thrombus Formation

    PubMed Central

    Metcalfe, Clive; Ramasubramoni, Anjana; Pula, Giordano; Harper, Matthew T.; Mundell, Stuart J.; Coxon, Carmen H.

    2016-01-01

    Thioredoxin (Trx) is an oxidoreductase with important physiological function. Imbalances in the NADPH/thioredoxin reductase/thioredoxin system are associated with a number of pathologies, particularly cancer, and a number of clinical trials for thioredoxin and thioredoxin reductase inhibitors have been carried out or are underway. Due to the emerging role and importance of oxidoreductases for haemostasis and the current interest in developing inhibitors for clinical use, we thought it pertinent to assess whether inhibition of the NADPH/thioredoxin reductase/thioredoxin system affects platelet function and thrombosis. We used small molecule inhibitors of Trx (PMX 464 and PX-12) to determine whether Trx activity influences platelet function, as well as an unbiased proteomics approach to identify potential Trx substrates on the surface of platelets that might contribute to platelet reactivity and function. Using LC-MS/MS we found that PMX 464 and PX-12 affected the oxidation state of thiols in a number of cell surface proteins. Key surface receptors for platelet adhesion and activation were affected, including the collagen receptor GPVI and the von Willebrand factor receptor, GPIb. To experimentally validate these findings we assessed platelet function in the presence of PMX 464, PX-12, and rutin (a selective inhibitor of the related protein disulphide isomerase). In agreement with the proteomics data, small molecule inhibitors of thioredoxin selectively inhibited GPVI-mediated platelet activation, and attenuated ristocetin-induced GPIb-vWF-mediated platelet agglutination, thus validating the findings of the proteomics study. These data reveal a novel role for thioredoxin in regulating platelet reactivity via proteins required for early platelet responses at sites of vessel injury (GPVI and GPIb). This work also highlights a potential opportunity for repurposing of PMX 464 and PX-12 as antiplatelet agents. PMID:27716777

  13. Thioredoxin Inhibitors Attenuate Platelet Function and Thrombus Formation.

    PubMed

    Metcalfe, Clive; Ramasubramoni, Anjana; Pula, Giordano; Harper, Matthew T; Mundell, Stuart J; Coxon, Carmen H

    2016-01-01

    Thioredoxin (Trx) is an oxidoreductase with important physiological function. Imbalances in the NADPH/thioredoxin reductase/thioredoxin system are associated with a number of pathologies, particularly cancer, and a number of clinical trials for thioredoxin and thioredoxin reductase inhibitors have been carried out or are underway. Due to the emerging role and importance of oxidoreductases for haemostasis and the current interest in developing inhibitors for clinical use, we thought it pertinent to assess whether inhibition of the NADPH/thioredoxin reductase/thioredoxin system affects platelet function and thrombosis. We used small molecule inhibitors of Trx (PMX 464 and PX-12) to determine whether Trx activity influences platelet function, as well as an unbiased proteomics approach to identify potential Trx substrates on the surface of platelets that might contribute to platelet reactivity and function. Using LC-MS/MS we found that PMX 464 and PX-12 affected the oxidation state of thiols in a number of cell surface proteins. Key surface receptors for platelet adhesion and activation were affected, including the collagen receptor GPVI and the von Willebrand factor receptor, GPIb. To experimentally validate these findings we assessed platelet function in the presence of PMX 464, PX-12, and rutin (a selective inhibitor of the related protein disulphide isomerase). In agreement with the proteomics data, small molecule inhibitors of thioredoxin selectively inhibited GPVI-mediated platelet activation, and attenuated ristocetin-induced GPIb-vWF-mediated platelet agglutination, thus validating the findings of the proteomics study. These data reveal a novel role for thioredoxin in regulating platelet reactivity via proteins required for early platelet responses at sites of vessel injury (GPVI and GPIb). This work also highlights a potential opportunity for repurposing of PMX 464 and PX-12 as antiplatelet agents.

  14. The Auroral Field-aligned Acceleration - Cluster Results

    NASA Astrophysics Data System (ADS)

    Vaivads, A.; Cluster Auroral Team

    The four Cluster satellites cross the auroral field lines at altitudes well above most of acceleration region. Thus, the orbit is appropriate for studies of the generator side of this region. We consider the energy transport towards the acceleration region and different mechanisms for generating the potential drop. Using data from Cluster we can also for the first time study the dynamics of the generator on a minute scale. We present data from a few auroral field crossings where Cluster are in conjunction with DMSP satellites. We use electric and magnetic field data to estimate electrostatic po- tential along the satellite orbit, Poynting flux as well as the presence of plasma waves. These we can compare with data from particle and wave instruments on Cluster and on low latitude satellites to try to make a consistent picture of the acceleration region formation in these cases. Preliminary results show close agreement both between in- tegrated potential values at Cluster and electron peak energies at DMSP as well as close agreement between the integrated Poynting flux values at Cluster and the elec- tron energy flux at DMSP. At the end we draw a parallels between auroral electron acceleration and electron acceleration at the magnetopause.

  15. Oxidation and formation of deposit precursors in hydrocarbon fuels

    NASA Technical Reports Server (NTRS)

    Mayo, F. R.; Lan, B.; Cotts, D. B.; Buttrill, S. E., Jr.; St.john, G. A.

    1983-01-01

    The oxidation of two jet turbine fuels and some pure hydrocarbons was studied at 130 C with and without the presence of small amounts of N-methyl pyrrole (NMP) or indene. Tendency to form solid-deposit precursors was studied by measuring soluble gum formation as well as dimer and trimer formation using field ionization mass spectrometry. Pure n-dodecane oxidized fastest and gave the smallest amount of procursors. An unstable fuel oil oxidized much slower but formed large amounts of precursors. Stable Jet A fuel oxidized slowest and gave little precursors. Indene either retarded or accelerated the oxidation of n-dodecane, depending on its concentration, but always caused more gum formation. The NMP greatly retarded n-dodecane oxidation but accelerated Jet A oxidation and greatly increased the latter's gum formation. In general, the additive reacted faster and formed most of the gum. Results are interpreted in terms of classical cooxidation theory. The effect of oxygen pressure on gum formation is also reported.

  16. A case of dilated cardiomyopathy with massive left ventricular thrombus after use of a sibutramine-containing slimming product.

    PubMed

    Heo, Seung Hye; Kang, Min-Ho

    2013-09-01

    Sibutramine, which acts as an anti-obesity drug by inhibiting reuptake of serotonin and norepinephrine, has now been banned due to cardiovascular adverse effects. However, despite being banned, it is not uncommon for people to purchase products with sibutramine or its analogues used as adulterants in non-prescription slimming products or health foods available on the internet. Sibutramine has been associated with rare but serious adverse reactions such as cardiac arrhythmia including QT interval prolongation, myocardial infarction, and cardiomyopathy, as well as increases in blood pressure and pulse rate. Here, we report a case of a 32-year-old male who presented with dilated cardiomyopathy with massive left ventricular thrombus after taking unauthorized sibutramine-containing slimming pills sold over the internet.

  17. Introducing the pro-coagulant contact system in the numerical assessment of device-related thrombosis.

    PubMed

    Méndez Rojano, Rodrigo; Mendez, Simon; Nicoud, Franck

    2018-06-01

    Thrombosis is a major concern in blood-coated medical devices. Contact activation, which is the initial part of the coagulation cascade in device-related thrombosis, is not considered in current thrombus formation models. In the present study, pro-coagulant reactions including the contact activation system are coupled with a fluid solver in order to evaluate the potential of the contact system to initiate thrombin production. The biochemical/fluid model is applied to a backward-facing step configuration, a flow configuration that frequently appears in medical devices. In contrast to the in vivo thrombosis models in which a specific thrombotic zone (injury region) is set a priori by the user to initiate the coagulation reaction, a reactive surface boundary condition is applied to the whole device wall. Simulation results show large thrombin concentration in regions related to recirculation zones without the need of an a priori knowledge of the thrombus location. The numerical results align well with the regions prone to thrombosis observed in experimental results reported in the literature. This approach could complement thrombus formation models that take into account platelet activity and thrombus growth to optimize a wide range of medical devices.

  18. Investigation of accelerated stress factors and failure/degradation mechanisms in terrestrial solar cells

    NASA Technical Reports Server (NTRS)

    Lathrop, J. W.

    1983-01-01

    Results of an ongoing research program into the reliability of terrestrial solar cells are presented. Laboratory accelerated testing procedures are used to identify failure/degradation modes which are then related to basic physical, chemical, and metallurgical phenomena. In the most recent tests, ten different types of production cells, both with and without encapsulation, from eight different manufacturers were subjected to a variety of accelerated tests. Results indicated the presence of a number of hitherto undetected failure mechanisms, including Schottky barrier formation at back contacts and loss of adhesion of grid metallization. The mechanism of Schottky barrier formation is explained by hydrogen, formed by the dissociation of water molecules at the contact surface, diffusing to the metal semiconductor interface. This same mechanism accounts for the surprising increase in sensitivity to accelerated stress conditions that was observed in some cells when encapsulated.

  19. Fully Implict Magneto-hydrodynamics Simulations of Coaxial Plasma Accelerators

    DOE PAGES

    Subramaniam, Vivek; Raja, Laxminarayan L.

    2017-01-05

    The resistive Magneto-Hydrodynamic (MHD) model describes the behavior of a strongly ionized plasma in the presence of external electric and magnetic fields. We developed a fully implicit MHD simulation tool to solve the resistive MHD governing equations in the context of a cell-centered finite-volume scheme. The primary objective of this study is to use the fully-implicit algorithm to obtain insights into the plasma acceleration and jet formation processes in Coaxial Plasma accelerators; electromagnetic acceleration devices that utilize self-induced magnetic fields to accelerate thermal plasmas to large velocities. We also carry out plasma-surface simulations in order to study the impact interactionsmore » when these high velocity plasma jets impinge on target material surfaces. Scaling studies are carried out to establish some basic functional relationships between the target-stagnation conditions and the current discharged between the coaxial electrodes.« less

  20. Heavy ion acceleration in the radiation pressure acceleration and breakout afterburner regimes

    NASA Astrophysics Data System (ADS)

    Petrov, G. M.; McGuffey, C.; Thomas, A. G. R.; Krushelnick, K.; Beg, F. N.

    2017-07-01

    We present a theoretical study of heavy ion acceleration from ultrathin (20 nm) gold foil irradiated by high-intensity sub-picosecond lasers. Using two-dimensional particle-in-cell simulations, three laser systems are modeled that cover the range between femtosecond and picosecond pulses. By varying the laser pulse duration we observe a transition from radiation pressure acceleration (RPA) to the relativistic induced transparency (RIT) regime for heavy ions akin to light ions. The underlying physics of beam formation and acceleration is similar for light and heavy ions, however, nuances of the acceleration process make the heavy ions more challenging. A more detailed study involving variation of peak laser intensity I 0 and pulse duration τFWHM revealed that the transition point from RPA to RIT regime depends on the peak laser intensity on target and occurs for pulse duration {τ }{{F}{{W}}{{H}}{{M}}}{{R}{{P}}{{A}}\\to {{R}}{{I}}{{T}}}[{{f}}{{s}}]\\cong 210/\\sqrt{{I}0[{{W}} {{{cm}}}-2]/{10}21}. The most abundant gold ion and charge-to-mass ratio are Au51+ and q/M ≈ 1/4, respectively, half that of light ions. For ultrathin foils, on the order of one skin depth, we established a linear scaling of the maximum energy per nucleon (E/M)max with (q/M)max, which is more favorable than the quadratic one found previously. The numerical simulations predict heavy ion beams with very attractive properties for applications: high directionality (<10° half-angle), high fluxes (>1011 ions sr-1) and energy (>20 MeV/nucleon) from laser systems delivering >20 J of energy on target.

  1. The role of platelet and endothelial GARP in thrombosis and hemostasis.

    PubMed

    Vermeersch, Elien; Denorme, Frederik; Maes, Wim; De Meyer, Simon F; Vanhoorelbeke, Karen; Edwards, Justin; Shevach, Ethan M; Unutmaz, Derya; Fujii, Hodaka; Deckmyn, Hans; Tersteeg, Claudia

    2017-01-01

    Glycoprotein-A Repetitions Predominant protein (GARP or LRRC32) is present on among others human platelets and endothelial cells. Evidence for its involvement in thrombus formation was suggested by full knockout of GARP in zebrafish. To evaluate the role of GARP in platelet physiology and in thrombus formation using platelet and endothelial conditional GARP knock out mice. Platelet and endothelial specific GARP knockout mice were generated using the Cre-loxP recombination system. The function of platelets without GARP was measured by flow cytometry, spreading analysis and aggregometry using PAR4-activating peptide and collagen related peptide. Additionally, clot retraction and collagen-induced platelet adhesion and aggregation under flow were analyzed. Finally, in vivo tail bleeding time, occlusion time of the mesenteric and carotid artery after FeCl3-induced thrombosis were determined in platelet and endothelial specific GARP knock out mice. Platelet specific GARP knockout mice had normal surface GPIb, GPVI and integrin αIIb glycoprotein expression. Although GARP expression was increased upon platelet activation, platelets without GARP displayed normal agonist induced activation, spreading on fibrinogen and aggregation responses. Furthermore, absence of GARP on platelets did not influence clot retraction and had no impact on thrombus formation on collagen-coated surfaces under flow. In line with this, neither the tail bleeding time nor the occlusion time in the carotid- and mesenteric artery after FeCl3-induced thrombus formation in platelet or endothelial specific GARP knock out mice were affected. Evidence is provided that platelet and endothelial GARP are not important in hemostasis and thrombosis in mice.

  2. Mechanical valve obstruction: Review of diagnostic and treatment strategies

    PubMed Central

    Salamon, Jason; Munoz-Mendoza, Jerson; Liebelt, Jared J; Taub, Cynthia C

    2015-01-01

    Prosthetic valve obstruction (PVO) is a rare but feared complication of mechanical valve replacement. Diagnostic evaluation should focus on differentiating prosthetic valve thrombosis (PVT) from pannus formation, as their treatment options differ. History of sub-optimal anti-coagulation and post-op time course to development of PVO are useful clinical characteristics in differentiating thrombus from pannus formation. Treatment of PVT is influenced by the patient’s symptoms, valve location, degree of obstruction and thrombus size and may include thrombolysis or surgical intervention. Alternatively, pannus formation requires surgical intervention. The purpose of this article is to review the pathophysiology, epidemiology, diagnostic approach and treatment options for aortic and mitral valve PVO. PMID:26730292

  3. Accelerated Near-Threshold Fatigue Crack Growth Behavior of an Aluminum Powder Metallurgy Alloy

    NASA Technical Reports Server (NTRS)

    Piascik, Robert S.; Newman, John A.

    2002-01-01

    Fatigue crack growth (FCG) research conducted in the near threshold regime has identified a room temperature creep crack growth damage mechanism for a fine grain powder metallurgy (PM) aluminum alloy (8009). At very low DK, an abrupt acceleration in room temperature FCG rate occurs at high stress ratio (R = Kmin/Kmax). The near threshold accelerated FCG rates are exacerbated by increased levels of Kmax (Kmax less than 0.4 KIC). Detailed fractographic analysis correlates accelerated FCG with the formation of crack-tip process zone micro-void damage. Experimental results show that the near threshold and Kmax influenced accelerated crack growth is time and temperature dependent.

  4. Orbit selection of nanosatellite formation in term of fuel consumption

    NASA Astrophysics Data System (ADS)

    Pimnoo, Ammarin; Hiraki, Koju

    In nanosatellite formation mission design, orbit selection is a necessary factor. Fuel consumption is also necessary to maintain the orbit. Therefore, the best orbit should be the one of minimum fuel consumption for nanosatellite formation. The purpose of this paper is to provide a convenient way to estimate fuel consumption for a nanosatellite to keep formation flying. The formation is disturbed by J _{2} perturbation and other perturbing accelerations. Firstly, the Hill-Clohessy-Wiltshire equations are used in the analysis. Gaussian variation of parameters is included into the Hill’s equation to analyze the variation of Kaplerian orbital elements. The J _{2} perturbation and other perturbing accelerations such as atmospheric drag, solar-radiation pressure and third-body perturbations are considered. Thus, a linear model based on Hill’s equation is established to estimate fuel consumption. Finally, an example of the best orbit for formation flying with minimum fuel consumption shall be presented.

  5. Reduced Contact Hour Accelerated Courses and Student Learning

    ERIC Educational Resources Information Center

    Thornton, Barry; Demps, Julius; Jadav, Arpita

    2017-01-01

    Undergraduate instruction in the Davis College of Business at Jacksonville University utilizes two course delivery methods. Traditional daytime classes are 15 weeks long and have approximately 40 contact hours, while evening courses are offered in the Accelerated Degree program in a compressed 8-week format with 24 contact hours. The curriculum is…

  6. Mass-Discrepancy Acceleration Relation: A Natural Outcome of Galaxy Formation in Cold Dark Matter Halos.

    PubMed

    Ludlow, Aaron D; Benítez-Llambay, Alejandro; Schaller, Matthieu; Theuns, Tom; Frenk, Carlos S; Bower, Richard; Schaye, Joop; Crain, Robert A; Navarro, Julio F; Fattahi, Azadeh; Oman, Kyle A

    2017-04-21

    We analyze the total and baryonic acceleration profiles of a set of well-resolved galaxies identified in the eagle suite of hydrodynamic simulations. Our runs start from the same initial conditions but adopt different prescriptions for unresolved stellar and active galactic nuclei feedback, resulting in diverse populations of galaxies by the present day. Some of them reproduce observed galaxy scaling relations, while others do not. However, regardless of the feedback implementation, all of our galaxies follow closely a simple relationship between the total and baryonic acceleration profiles, consistent with recent observations of rotationally supported galaxies. The relation has small scatter: Different feedback implementations-which produce different galaxy populations-mainly shift galaxies along the relation rather than perpendicular to it. Furthermore, galaxies exhibit a characteristic acceleration g_{†}, above which baryons dominate the mass budget, as observed. These observations, consistent with simple modified Newtonian dynamics, can be accommodated within the standard cold dark matter paradigm.

  7. Solar Energetic Particle Events and CME Accelerations in the Low Corona: MLSO Observations

    NASA Astrophysics Data System (ADS)

    St Cyr, O. C.; Kahler, S. W.; Richardson, I. G.; Cane, H. V.; Xie, H.; Burkepile, J.

    2016-12-01

    The low solar corona (< 2.5 Rs) is the region in which maximum coronal mass ejection (CME) acceleration occurs and where Type II radio observations suggest that shock formation occurs (Mäkelä et al., 2015). It is therefore a key region for investigations of solar energetic particle (SEP) acceleration by CME-driven shocks. Observations very low in the corona are necessary to detect the rapid CME accelerations leading to shock formation and to assess the speeds of CMEs through the middle corona. However, these observations cannot be made by space borne coronagraphs in which CME trajectories above the occulting disk are usually characterized by a single (constant) speed: e.g., 80% of the speeds in the compilation of SMM CMEs (Burkepile and St. Cyr, 1993) and SOHO LASCO CMEs (St. Cyr et al., 2000). The Mk3/Mk4/K-Cor coronameters at the Mauna Loa Solar Observatory are able to measure the initial accelerations of CMEs low in the corona (i.e., < 2 Rs). We examine a subset of CMEs that were associated with SEP events between 1980-present. The subset is based on the CME launch occurring between 16 UT - 01 UT - the MLSO observing window. In most cases, the CME accelerations are significantly larger than those measured by spaceborne coronagraphs (e.g., SMM, Solwind, LASCO, SECCHI). We will present the preliminary results of a comparison of the SEP parameters with initial CME accelerations in the MLSO coronagraph field of view.

  8. Cardiopulmonary bypass-assisted surgery for the treatment of Xp11.2 translocation/TFE3 gene fusion renal cell carcinoma with a tumor thrombus within the inferior vena cava: A case report.

    PubMed

    Zhu, Guanchen; Qiu, Xuefeng; Chen, Xianchen; Liu, Guangxiang; Zhang, Gutian; Gan, Weidong; Guo, Hongqian

    2015-12-01

    Renal cell carcinoma (RCC) accounts for 85-90% of kidney cancers, which in turn account for 2-3% of all malignant tumors in adults. Xp11.2 translocation/TFE3 gene fusion RCC is currently classified as a distinct type of RCC. RCC is capable of invading the renal vein and inferior vena cava to form a tumor thrombus. The incidence of RCC with tumor thrombi within the renal vein or inferior vena cava is 7-10% in China. In the present case report, the patient underwent radical resection of the renal tumor and removal of the tumor thrombus, assisted by cardiopulmonary bypass, for the treatment of Xp11.2 translocation/TFE3 gene fusion RCC. The patient was followed-up for 12 months subsequent to treatment. The patient's renal function remained within the normal range, and computed tomography examination revealed no evidence of disease recurrence or metastases. The present case report aimed to provide a reference for the development of guidelines for the diagnosis and treatment of Xp11.2 translocation/TFE3 gene fusion RCC.

  9. Cardiopulmonary bypass-assisted surgery for the treatment of Xp11.2 translocation/TFE3 gene fusion renal cell carcinoma with a tumor thrombus within the inferior vena cava: A case report

    PubMed Central

    ZHU, GUANCHEN; QIU, XUEFENG; CHEN, XIANCHEN; LIU, GUANGXIANG; ZHANG, GUTIAN; GAN, WEIDONG; GUO, HONGQIAN

    2015-01-01

    Renal cell carcinoma (RCC) accounts for 85–90% of kidney cancers, which in turn account for 2–3% of all malignant tumors in adults. Xp11.2 translocation/TFE3 gene fusion RCC is currently classified as a distinct type of RCC. RCC is capable of invading the renal vein and inferior vena cava to form a tumor thrombus. The incidence of RCC with tumor thrombi within the renal vein or inferior vena cava is 7–10% in China. In the present case report, the patient underwent radical resection of the renal tumor and removal of the tumor thrombus, assisted by cardiopulmonary bypass, for the treatment of Xp11.2 translocation/TFE3 gene fusion RCC. The patient was followed-up for 12 months subsequent to treatment. The patient's renal function remained within the normal range, and computed tomography examination revealed no evidence of disease recurrence or metastases. The present case report aimed to provide a reference for the development of guidelines for the diagnosis and treatment of Xp11.2 translocation/TFE3 gene fusion RCC. PMID:26788164

  10. Gravitomagnetic Acceleration of Black Hole Accretion Disk Matter to Polar Jets

    NASA Astrophysics Data System (ADS)

    Poirier, John; Mathews, Grant

    2015-04-01

    It is shown that the motion of the neutral masses in an accretion disk orbiting a black hole creates a magnetic-like (gravitomagnetic) field that vertically accelerates neutral particles near the accretion disk away from the disk and then inward toward the axis of the accretion disk. Moreover, as the accelerated material nears the axis, a frame-dragging effect twists the trajectories around the axis thus contributing to the formation of a narrow polar jet emanating from the poles.

  11. Accelerated bone formation on photo-induced hydrophilic titanium implants: an experimental study in the dog mandible.

    PubMed

    Hirakawa, Yuko; Jimbo, Ryo; Shibata, Yasuaki; Watanabe, Ikuya; Wennerberg, Ann; Sawase, Takashi

    2013-08-01

    The purpose of this study was to investigate the effect of photo-induced hydrophilic titanium dioxide (TiO₂) on serum fibronectin (sFN) attachment, and further to evaluate initial osseointegration responses in the dog mandibles. To apply the anatase TiO₂ film, plasma source ion implantation (PSII) method followed by annealing was employed for the titanium disks and implants, which were then illuminated with UV-A for 24 h for the experimental groups. Non-deposited titanium disks and implants were prepared for the control group. Surface characterization was performed using the interferometer and contact angle analyzer. The attachments of sFN were evaluated using fluorescence emission analysis. Thereafter both groups of implants were placed in the mandible of six beagle dogs. Bone response was investigated with histological and histomorphometrical analyses after periods of 2 and 4 weeks. The experimental groups exhibited strong hydrophilicity under UV-A illumination and showed significant improvement in sFN attachment. And further, the experimental implants enhanced the bone formation with the bone-to-implant contact of 42.7% after 2 weeks of healing (control: 28.4%). The combined applications of plasma fibronectin and PSII to produce hydrophilic titanium surfaces could accelerate early osseointegration. © 2012 John Wiley & Sons A/S.

  12. Selective inhibition by a synthetic hirudin peptide of fibrin-dependent thrombosis in baboons

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Cadroy, Y.; Hanson, S.R.; Harker, L.A.

    1991-02-15

    To determine the importance of the thrombin substrate recognition exosite for fibrinogen binding in the formation of both arterial and venous thrombi the authors evaluated the antithrombotic effects of the tyrosine-sulfated dodecapeptide from residues 53-64 of hirudin (H peptide) in a nonhuman primate model. This peptide was studied because it inhibits thrombin cleavages of fibrinogen by simple competition without blocking enzyme catalytic-site function. When an exteriorized arteriovenous access shunt model was used in baboons (Papio anubis), thrombus formation was induced by placing a thrombogenic device made of (i) a segment of tubing coated covalently with type I collagen, which generatedmore » platelet-rich thrombi under arterial flow conditions, and (ii) two subsequent annular regions of flow expansion that produced fibrin-rich thrombi typically associated with venous valves and veins. Thrombus formation was quantified by measurements of {sup 111}In-labeled platelet and {sup 125}I-labeled fibrinogen deposition in both arterial-flow and venous-flow portions of the device. These finding suggest that, by competitive inhibition of fibrinogen binding to thrombin, fibrin-rich venous-type thrombus formation may be selectively prevented. This strategy may be therapeutically attractive for preserving normal platelet function when conventional anticoagulant therapy is contraindicated.« less

  13. Annular structures formed in a beam of ions during their collective acceleration in a system with dielectric anode

    NASA Astrophysics Data System (ADS)

    Lopatin, V. S.; Remnev, G. E.; Martynenko, A. A.

    2017-05-01

    We have studied the collective acceleration of protons and deuterons in an electron beam emitted from plasma formed at the surface of a dielectric anode insert. The experiments were performed with a pulsed electron accelerator operating at an accelerating voltage up to 1 MV, current amplitude up to 40 kA, and pulse duration of 50 ns. Reduction of the accelerating voltage pulse front width and optimization of the diode unit and drift region ensured the formation of several annular structures in the electron beam. As a result, up to 50% of the radioactivity induced in a copper target was concentrated in a ring with 4.5-cm diameter and 0.2-cm width. The formation of high energy density in these circular traces and the appearance of an axial component of the self-generated magnetic field of the electron beam are related with the increasing efficiency of acceleration of the most intense group of ions.

  14. Formation Flying for Distributed InSAR

    NASA Technical Reports Server (NTRS)

    Scharf, Daniel P.; Murray, Emmanuell A.; Ploen, Scott R.; Gromov, Konstantin G.; Chen, Curtis W.

    2006-01-01

    We consider two spacecraft flying in formation to create interferometric synthetic aperture radar (InSAR). Several candidate orbits for such in InSar formation have been previously determined based on radar performance and Keplerian orbital dynamics. However, with out active control, disturbance-induced drift can degrade radar performance and (in the worst case) cause a collision. This study evaluates the feasibility of operating the InSAR spacecraft as a formation, that is, with inner-spacecraft sensing and control. We describe the candidate InSAR orbits, design formation guidance and control architectures and algorithms, and report the (Delta)(nu) and control acceleration requirements for the candidate orbits for several tracking performance levels. As part of determining formation requirements, a formation guidance algorithm called Command Virtual Structure is introduced that can reduce the (Delta)(nu) requirements compared to standard Leader/Follower formation approaches.

  15. Antiplatelet Activity of Morus alba Leaves Extract, Mediated via Inhibiting Granule Secretion and Blocking the Phosphorylation of Extracellular-Signal-Regulated Kinase and Akt

    PubMed Central

    Rhee, Man Hee; Sung, Yoon-Young; Yang, Won-Kyung; Kim, Seung Hyung; Kim, Ho-Kyoung

    2014-01-01

    Ethnopharmacological Relevance. Morus alba L. leaves (MAE) have been used in fork medicine for the treatment of beriberi, edema, diabetes, hypertension, and atherosclerosis. However, underlying mechanism of MAE on cardiovascular protection remains to be elucidated. Therefore, we investigated whether MAE affect platelet aggregation and thrombosis. Materials and Methods. The anti-platelet activity of MAE was studied using rat platelets. The extent of anti-platelet activity of MAE was assayed in collagen-induced platelet aggregation. ATP and serotonin release was carried out. The activation of integrin α IIb β 3 and phosphorylation of signaling molecules, including MAPK and Akt, were investigated with cytofluorometer and immunoblotting, respectively. The thrombus formation in vivo was also evaluated in arteriovenous shunt model of rats. Results. HPLC chromatographic analysis revealed that MAE contained rutin and isoquercetin. MAE dose-dependently inhibited collagen-induced platelet aggregation. MAE also attenuated serotonin secretion and thromboxane A2 formation. In addition, the extract in vivo activity showed that MAE at 100, 200, and 400 mg/kg significantly and dose-dependently attenuated thrombus formation in rat arterio-venous shunt model by 52.3% (P < 0.001), 28.3% (P < 0.01), and 19.1% (P < 0.05), respectively. Conclusions. MAE inhibit platelet activation, TXB2 formation, serotonin secretion, aggregation, and thrombus formation. The plant extract could be considered as a candidate to anti-platelet and antithrombotic agent. PMID:24701244

  16. Radiobiological research at JINR's accelerators

    NASA Astrophysics Data System (ADS)

    Krasavin, E. A.

    2016-04-01

    The half-a-century development of radiobiological studies at the Joint Institute for Nuclear Research (JINR) is reviewed on a stage-by-stage basis. With the use of the institute's accelerators, some key aspects of radiation biology have been settled, including the relative biological effectiveness (RBE) of various types of ionizing radiation with different physical characteristics; radiation-induced mutagenesis mechanisms, and the formation and repair of genetic structure damage. Practical space radiobiology problems that can be solved using high-energy charged particles are discussed.

  17. Combined sustained release of BMP2 and MMP10 accelerates bone formation and mineralization of calvaria critical size defect in mice.

    PubMed

    Reyes, Ricardo; Rodríguez, Jose Antonio; Orbe, Josune; Arnau, María Rosa; Évora, Carmen; Delgado, Araceli

    2018-11-01

    The effect of dual delivery of bone morphogenetic protein-2 (BMP-2) and matrix metalloproteinase 10 (MMP10) on bone regeneration was investigated in a murine model of calvarial critical-size defect, hypothesizing that it would result in an enhanced bone formation. Critical-size calvarial defects (4 mm diameter) were created in mice and PLGA microspheres preloaded with either BMP-2, MMP10 or a microsphere combination of both were transplanted into defect sites at different doses. Empty microspheres were used as the negative control. Encapsulation efficiency was assessed and in vivo release kinetics of BMP-2 and MMP10 were examined over 14 days. Histological analyses were used to analyze bone formation after four and eight weeks. Combination with MMP10 (30 ng) significantly enhanced BMP-2 (600 ng)-mediated osteogenesis, as confirmed by the increase in percentage of bone fill (p < .05) at four weeks. Moreover, it also increased mineral apposition rate (p < .05), measured by double labeling with tetracycline and calceine. MMP10 accelerates bone repair by enhancing BMP-2-promoted bone healing and improving the mineralization rate. In conclusion combination of MMP10 and BMP-2 may become a promising strategy for repair and regeneration of bone defects.

  18. Effect of Blood Shear Forces on Platelet Mediated Thrombosis Inside Arterial Stenosis.

    NASA Astrophysics Data System (ADS)

    Maalej, Nabil

    Shear induced activation of platelets plays a major role in the onset of thrombosis in atherosclerotic arteries. Blood hemodynamics and its effect on platelet kinetics has been studied mainly in in vitro and in ex vivo experiments. We designed new in vivo methods to study blood hemodynamic effects on platelet kinetics in canine stenosed carotid arteries. A carotid artery-jugular vein anastomotic shunt was produced. Intimal damage and controlled variations in the degree of stenosis were produced on the artery. An inflatable cuff was placed around the jugular vein to control vascular resistance. An electromagnetic flowmeter was used to measure blood flow. Doppler ultrasound crystals were used to measure the velocity profiles inside and distal to the stenosis. Stenosis geometry was obtained using digital subtraction angiography and quantitative arteriography. Using these measurements we calculated the wall shear stress using the finite difference solution of the Navier-Stokes equations. To study platelet kinetics, autologous platelets were labeled with Indium Oxine and injected IV. A collimated Nal gamma counter was placed over the stenosis to detect radio-labeled platelet accumulation as platelet mediated thrombi formed in the stenosis. The radioactive count rate increased in an inverse parallel fashion to the decline in flow rate during thrombus formation. The platelet accumulation increased with the increase of percent stenosis and was maximal at the narrow portion of the stenosis. Acute thrombus formation leading to arterial occlusion was only observed for stenosis higher than 70 +/- 5%. Platelet accumulation rate was not significant until the pressure gradient across the stenosis exceeded 40 +/- 10 mmHg. Totally occlusive thrombus formation was only observed for shear stresses greater than a critical value of 100 +/- 10 Pa. Beyond this critical value acute platelet thrombus formation increased exponentially with shear. Increased shear stresses were found to

  19. Particle traps prevent adverse vascular and prothrombotic effects of diesel engine exhaust inhalation in men.

    PubMed

    Lucking, Andrew J; Lundbäck, Magnus; Barath, Stefan L; Mills, Nicholas L; Sidhu, Manjit K; Langrish, Jeremy P; Boon, Nicholas A; Pourazar, Jamshid; Badimon, Juan J; Gerlofs-Nijland, Miriam E; Cassee, Flemming R; Boman, Christoffer; Donaldson, Kenneth; Sandstrom, Thomas; Newby, David E; Blomberg, Anders

    2011-04-26

    In controlled human exposure studies, diesel engine exhaust inhalation impairs vascular function and enhances thrombus formation. The aim of the present study was to establish whether an exhaust particle trap could prevent these adverse cardiovascular effects in men. Nineteen healthy volunteers (mean age, 25±3 years) were exposed to filtered air and diesel exhaust in the presence or absence of a particle trap for 1 hour in a randomized, double-blind, 3-way crossover trial. Bilateral forearm blood flow and plasma fibrinolytic factors were assessed with venous occlusion plethysmography and blood sampling during intra-arterial infusion of acetylcholine, bradykinin, sodium nitroprusside, and verapamil. Ex vivo thrombus formation was determined with the use of the Badimon chamber. Compared with filtered air, diesel exhaust inhalation was associated with reduced vasodilatation and increased ex vivo thrombus formation under both low- and high-shear conditions. The particle trap markedly reduced diesel exhaust particulate number (from 150 000 to 300 000/cm(3) to 30 to 300/cm(3); P<0.001) and mass (320±10 to 7.2±2.0 μg/m(3); P<0.001), and was associated with increased vasodilatation, reduced thrombus formation, and an increase in tissue-type plasminogen activator release. Exhaust particle traps are a highly efficient method of reducing particle emissions from diesel engines. With a range of surrogate measures, the use of a particle trap prevents several adverse cardiovascular effects of exhaust inhalation in men. Given these beneficial effects on biomarkers of cardiovascular health, the widespread use of particle traps on diesel-powered vehicles may have substantial public health benefits and reduce the burden of cardiovascular disease.

  20. The role of platelet and endothelial GARP in thrombosis and hemostasis

    PubMed Central

    Vermeersch, Elien; Denorme, Frederik; Maes, Wim; De Meyer, Simon F.; Vanhoorelbeke, Karen; Edwards, Justin; Shevach, Ethan M.; Unutmaz, Derya; Fujii, Hodaka; Deckmyn, Hans; Tersteeg, Claudia

    2017-01-01

    Background Glycoprotein-A Repetitions Predominant protein (GARP or LRRC32) is present on among others human platelets and endothelial cells. Evidence for its involvement in thrombus formation was suggested by full knockout of GARP in zebrafish. Objectives To evaluate the role of GARP in platelet physiology and in thrombus formation using platelet and endothelial conditional GARP knock out mice. Methods Platelet and endothelial specific GARP knockout mice were generated using the Cre-loxP recombination system. The function of platelets without GARP was measured by flow cytometry, spreading analysis and aggregometry using PAR4-activating peptide and collagen related peptide. Additionally, clot retraction and collagen-induced platelet adhesion and aggregation under flow were analyzed. Finally, in vivo tail bleeding time, occlusion time of the mesenteric and carotid artery after FeCl3-induced thrombosis were determined in platelet and endothelial specific GARP knock out mice. Results Platelet specific GARP knockout mice had normal surface GPIb, GPVI and integrin αIIb glycoprotein expression. Although GARP expression was increased upon platelet activation, platelets without GARP displayed normal agonist induced activation, spreading on fibrinogen and aggregation responses. Furthermore, absence of GARP on platelets did not influence clot retraction and had no impact on thrombus formation on collagen-coated surfaces under flow. In line with this, neither the tail bleeding time nor the occlusion time in the carotid- and mesenteric artery after FeCl3-induced thrombus formation in platelet or endothelial specific GARP knock out mice were affected. Conclusions Evidence is provided that platelet and endothelial GARP are not important in hemostasis and thrombosis in mice. PMID:28278197

  1. Oral thrombin inhibitor aggravates platelet adhesion and aggregation during arterial thrombosis.

    PubMed

    Petzold, Tobias; Thienel, Manuela; Konrad, Ildiko; Schubert, Irene; Regenauer, Ron; Hoppe, Boj; Lorenz, Michael; Eckart, Annekathrin; Chandraratne, Sue; Lennerz, Carsten; Kolb, Christof; Braun, Daniel; Jamasbi, Janina; Brandl, Richard; Braun, Siegmund; Siess, Wolfgang; Schulz, Christian; Massberg, Steffen

    2016-11-30

    In patients with atrial fibrillation, oral anticoagulation with oral thrombin inhibitors (OTIs), in contrast to vitamin K antagonists (VKAs), associates with a modest increase in acute coronary syndromes (ACSs). Whether this observation is causatively linked to OTI treatment and, if so, whether OTI action is the result of a lower antithrombotic efficacy of OTI compared to VKA or reflects a yet undefined prothrombotic activity of OTI remain unclear. We analyzed platelet function in patients receiving OTI or dose-adapted VKA under static and flow conditions. In vivo, we studied arterial thrombosis in OTI-, VKA-, and vehicle-treated mice using carotid ligation and wire injury models. Further, we examined thrombus formation on human atherosclerotic plaque homogenates under arterial shear to address the relevance to human pathology. Under static conditions, aggregation in the presence of ristocetin was increased in OTI-treated blood, whereas platelet reactivity and aggregation to other agonists were only marginally affected. Under flow conditions, firm platelet adhesion and thrombus formation on von Willebrand factor, collagen, and human atherosclerotic plaque were increased in the presence of OTI in comparison to VKA. OTI treatment was associated with increased thrombus formation in injured carotid arteries of mice. Inhibition or ablation of GPIbα-thrombin interactions abolished the effect of OTI on thrombus formation, suggesting a mechanistic role of the platelet receptor GPIbα and its thrombin-binding site. The effect of OTI was also abrogated in the presence of aspirin. In summary, OTI treatment has prothrombotic activity that might contribute to the increase in ACS observed clinically in patients. Copyright © 2016, American Association for the Advancement of Science.

  2. The Relationship Between Pulsatile Flow Impingement and Intraluminal Thrombus Deposition in Abdominal Aortic Aneurysms.

    PubMed

    Lozowy, Richard J; Kuhn, David C S; Ducas, Annie A; Boyd, April J

    2017-03-01

    Direct numerical simulations were performed on four patient-specific abdominal aortic aneurysm (AAA) geometries and the resulting pulsatile blood flow dynamics were compared to aneurysm shape and correlated with intraluminal thrombus (ILT) deposition. For three of the cases, turbulent vortex structures impinged/sheared along the anterior wall and along the posterior wall a zone of recirculating blood formed. Within the impingement region the AAA wall was devoid of ILT and remote to this region there was an accumulation of ILT. The high wall shear stress (WSS) caused by the impact of vortexes is thought to prevent the attachment of ILT. WSS from impingement is comparable to peak-systolic WSS in a normal-sized aorta and therefore may not damage the wall. Expansion occurred to a greater extent in the direction of jet impingement and the wall-normal force from the continuous impact of vortexes may contribute to expansion. It was shown that the impingement region has low oscillatory shear index (OSI) and recirculation zones can have either low or high OSI. No correlation could be identified between OSI and ILT deposition since different flow dynamics can have similar OSI values.

  3. Interactions of Histophilus somni with Host Cells.

    PubMed

    Behling-Kelly, Erica; Rivera-Rivas, Jose; Czuprynski, Charles J

    2016-01-01

    Histophilus somni resides as part of the normal microflora in the upper respiratory tract of healthy cattle. From this site, the organism can make its way into the lower respiratory tract, where it is one of the important bacterial agents of the respiratory disease complex. If H. somni cells disseminate to the bloodstream, they frequently result in thrombus formation. A series of in vitro investigations have examined potential mechanisms that might contribute to such thrombus formation. Earlier work showed that H. somni can stimulate some bovine endothelial cells to undergo apoptosis. More recent studies indicate that H. somni stimulates endothelial cell tissue factor activity and disrupts intercellular junctions. The net effect is to enhance procoagulant activity on the endothelium surface and to make the endothelial monolayer more permeable to molecules, leukocytes, and perhaps H. somni cells. H. somni also activates bovine platelets, which also can enhance tissue factor activity on the endothelium surface. When exposed to H. somni, bovine neutrophils and mononuclear phagocytes form extracellular traps in vitro. Ongoing research is investigating how the interplay among endothelial cells, platelets, and leukocytes might contribute to the thrombus formation seen in infected cattle.

  4. Partially hydrolyzed guar gum supplement reduces high-fat diet increased blood lipids and oxidative stress and ameliorates FeCl3-induced acute arterial injury in hamsters

    PubMed Central

    Kuo, Dar-Chih; Hsu, Shih-Ping; Chien, Chiang-Ting

    2009-01-01

    Increased reactive oxygen species (ROS) and hyperlipidemia can promote arterial thrombus. We evaluated the potential of a partially hydrolyzed guar gum (PHGG) as dietary fiber on lipid profiles and FeCl3-induced arterial thrombosis in the high fat-diet fed hamsters. Our in vitro results found that PHGG is efficient to scavenge O2-•, H2O2, and HOCl. High fat-diet increased plasma triglyceride, total cholesterol, LDL, VLDL, methylguanidine and dityrosine level and accelerated FeCl3-induced arterial thrombosis formation (from 463 ± 51 to 303 ± 45 sec). Low dose PHGG supplement significantly decreased the total cholesterol, LDL, methylguanidine and dityrosine level and delayed the time for arterial thrombosis formation (528 ± 75 sec). High dose PHGG supplement decreased the level in triglyceride, total cholesterol, LDL and VLDL and further delayed the time for arterial thrombus (671 ± 36 sec). The increased Bax protein and decreased Bcl-2 and HSP-70 protein expression was found in the carotid and femoral arteries of high fat-diet hamsters. Low and high dose of PHGG supplement decreased Bax expression and increased Bcl-2 and HSP-70 protein expression. We found that FeCl3 significantly enhanced intercellular adhesion molecule-1 and 4-hydroxynonenal expression in the endothelial site of damaged artery after 150-sec FeCl3 stimulation. PHGG supplement decreased the endothelial ICAM-1 and 4-hydroxynonenal expression after 150-sec FeCl3 stimulation. Based on these results, we conclude that PHGG supplement can increase antioxidant protein expression and thus decrease oxidative stress induced arterial injury. PMID:19272178

  5. First muon acceleration using a radio-frequency accelerator

    NASA Astrophysics Data System (ADS)

    Bae, S.; Choi, H.; Choi, S.; Fukao, Y.; Futatsukawa, K.; Hasegawa, K.; Iijima, T.; Iinuma, H.; Ishida, K.; Kawamura, N.; Kim, B.; Kitamura, R.; Ko, H. S.; Kondo, Y.; Li, S.; Mibe, T.; Miyake, Y.; Morishita, T.; Nakazawa, Y.; Otani, M.; Razuvaev, G. P.; Saito, N.; Shimomura, K.; Sue, Y.; Won, E.; Yamazaki, T.

    2018-05-01

    Muons have been accelerated by using a radio-frequency accelerator for the first time. Negative muonium atoms (Mu- ), which are bound states of positive muons (μ+) and two electrons, are generated from μ+'s through the electron capture process in an aluminum degrader. The generated Mu- 's are initially electrostatically accelerated and injected into a radio-frequency quadrupole linac (RFQ). In the RFQ, the Mu- 's are accelerated to 89 keV. The accelerated Mu- 's are identified by momentum measurement and time of flight. This compact muon linac opens the door to various muon accelerator applications including particle physics measurements and the construction of a transmission muon microscope.

  6. Acute free-floating carotid artery thrombus causing stroke in a young patient: unique etiology and management using endovascular approach.

    PubMed

    Tan, Ai Peng; Taneja, Manish; Seah, Boon Heng; Leong, Hoe Nam; Venketasubramanian, Narayanaswamy

    2014-01-01

    Atherosclerotic disease accounts for 20%-30% of strokes in the general population. In young adults, it is an unexpected event and its causes involve diverse pathologies. Herein, we describe a unique case of acute embolic stroke in a young adult patient due to the presence of a large clot in the right common and internal carotid arteries, as a result of an extrinsic cause. Surgical clot retrieval was considered unsafe at that point in time in view of the active inflammatory changes surrounding the affected vessels. This was eventually treated with a novel endovascular technique, a unique alternative to open surgery, with excellent clinical outcome. To our knowledge, the penumbra system has never been used for thrombus removal in a nonacute setting. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  7. Electrostatic Steering Accelerates C3d:CR2 Association

    PubMed Central

    2016-01-01

    Electrostatic effects are ubiquitous in protein interactions and are found to be pervasive in the complement system as well. The interaction between complement fragment C3d and complement receptor 2 (CR2) has evolved to become a link between innate and adaptive immunity. Electrostatic interactions have been suggested to be the driving factor for the association of the C3d:CR2 complex. In this study, we investigate the effects of ionic strength and mutagenesis on the association of C3d:CR2 through Brownian dynamics simulations. We demonstrate that the formation of the C3d:CR2 complex is ionic strength-dependent, suggesting the presence of long-range electrostatic steering that accelerates the complex formation. Electrostatic steering occurs through the interaction of an acidic surface patch in C3d and the positively charged CR2 and is supported by the effects of mutations within the acidic patch of C3d that slow or diminish association. Our data are in agreement with previous experimental mutagenesis and binding studies and computational studies. Although the C3d acidic patch may be locally destabilizing because of unfavorable Coulombic interactions of like charges, it contributes to the acceleration of association. Therefore, acceleration of function through electrostatic steering takes precedence to stability. The site of interaction between C3d and CR2 has been the target for delivery of CR2-bound nanoparticle, antibody, and small molecule biomarkers, as well as potential therapeutics. A detailed knowledge of the physicochemical basis of C3d:CR2 association may be necessary to accelerate biomarker and drug discovery efforts. PMID:27092816

  8. Electrostatic Steering Accelerates C3d:CR2 Association.

    PubMed

    Mohan, Rohith R; Huber, Gary A; Morikis, Dimitrios

    2016-08-25

    Electrostatic effects are ubiquitous in protein interactions and are found to be pervasive in the complement system as well. The interaction between complement fragment C3d and complement receptor 2 (CR2) has evolved to become a link between innate and adaptive immunity. Electrostatic interactions have been suggested to be the driving factor for the association of the C3d:CR2 complex. In this study, we investigate the effects of ionic strength and mutagenesis on the association of C3d:CR2 through Brownian dynamics simulations. We demonstrate that the formation of the C3d:CR2 complex is ionic strength-dependent, suggesting the presence of long-range electrostatic steering that accelerates the complex formation. Electrostatic steering occurs through the interaction of an acidic surface patch in C3d and the positively charged CR2 and is supported by the effects of mutations within the acidic patch of C3d that slow or diminish association. Our data are in agreement with previous experimental mutagenesis and binding studies and computational studies. Although the C3d acidic patch may be locally destabilizing because of unfavorable Coulombic interactions of like charges, it contributes to the acceleration of association. Therefore, acceleration of function through electrostatic steering takes precedence to stability. The site of interaction between C3d and CR2 has been the target for delivery of CR2-bound nanoparticle, antibody, and small molecule biomarkers, as well as potential therapeutics. A detailed knowledge of the physicochemical basis of C3d:CR2 association may be necessary to accelerate biomarker and drug discovery efforts.

  9. A Model of RHIC Using the Unified Accelerator Libraries

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pilat, F.; Tepikian, S.; Trahern, C. G.

    1998-01-01

    The Unified Accelerator Library (UAL) is an object oriented and modular software environment for accelerator physics which comprises an accelerator object model for the description of the machine (SMF, for Standard Machine Format), a collection of Physics Libraries, and a Perl inte,face that provides a homo­geneous shell for integrating and managing these components. Currently available physics libraries include TEAPOT++, a collection of C++ physics modules conceptually derived from TEAPOT, and DNZLIB, a differential algebra package for map generation. This software environment has been used to build a flat model of RHIC which retains the hierarchical lat­tice description while assigning specificmore » characteristics to individual elements, such as measured field har­monics. A first application of the model and of the simulation capabilities of UAL has been the study of RHIC stability in the presence of siberian snakes and spin rotators. The building blocks of RHIC snakes and rotators are helical dipoles, unconventional devices that can not be modeled by traditional accelerator phys­ics codes and have been implemented in UAL as Taylor maps. Section 2 describes the RHIC data stores, Section 3 the RHIC SMF format and Section 4 the RHIC spe­cific Perl interface (RHIC Shell). Section 5 explains how the RHIC SMF and UAL have been used to study the RHIC dynamic behavior and presents detuning and dynamic aperture results. If the reader is not familiar with the motivation and characteristics of UAL, we include in the Appendix an useful overview paper. An example of a complete set of Perl Scripts for RHIC simulation can also be found in the Appendix.« less

  10. PARTICLE ACCELERATOR

    DOEpatents

    Teng, L.C.

    1960-01-19

    ABS>A combination of two accelerators, a cyclotron and a ring-shaped accelerator which has a portion disposed tangentially to the cyclotron, is described. Means are provided to transfer particles from the cyclotron to the ring accelerator including a magnetic deflector within the cyclotron, a magnetic shield between the ring accelerator and the cyclotron, and a magnetic inflector within the ring accelerator.

  11. Acceleration Modes and Transitions in Pulsed Plasma Accelerators

    NASA Technical Reports Server (NTRS)

    Polzin, Kurt A.; Greve, Christine M.

    2018-01-01

    Pulsed plasma accelerators typically operate by storing energy in a capacitor bank and then discharging this energy through a gas, ionizing and accelerating it through the Lorentz body force. Two plasma accelerator types employing this general scheme have typically been studied: the gas-fed pulsed plasma thruster and the quasi-steady magnetoplasmadynamic (MPD) accelerator. The gas-fed pulsed plasma accelerator is generally represented as a completely transient device discharging in approximately 1-10 microseconds. When the capacitor bank is discharged through the gas, a current sheet forms at the breech of the thruster and propagates forward under a j (current density) by B (magnetic field) body force, entraining propellant it encounters. This process is sometimes referred to as detonation-mode acceleration because the current sheet representation approximates that of a strong shock propagating through the gas. Acceleration of the initial current sheet ceases when either the current sheet reaches the end of the device and is ejected or when the current in the circuit reverses, striking a new current sheet at the breech and depriving the initial sheet of additional acceleration. In the quasi-steady MPD accelerator, the pulse is lengthened to approximately 1 millisecond or longer and maintained at an approximately constant level during discharge. The time over which the transient phenomena experienced during startup typically occur is short relative to the overall discharge time, which is now long enough for the plasma to assume a relatively steady-state configuration. The ionized gas flows through a stationary current channel in a manner that is sometimes referred to as the deflagration-mode of operation. The plasma experiences electromagnetic acceleration as it flows through the current channel towards the exit of the device. A device that had a short pulse length but appeared to operate in a plasma acceleration regime different from the gas-fed pulsed plasma

  12. Enhanced dimethyl phthalate biodegradation by accelerating phthalic acid di-oxygenation.

    PubMed

    Tang, Yingxia; Zhang, Yongming; Jiang, Ling; Yang, Chao; Rittmann, Bruce E

    2017-12-01

    The aerobic biodegradation of dimethyl phthalate (DMP) is initiated with two hydrolysis reactions that generate an intermediate, phthalic acid (PA), that is further biodegraded through a two-step di-oxygenation reaction. DMP biodegradation is inhibited when PA accumulates, but DMP's biodegradation can be enhanced by adding an exogenous electron donor. We evaluated the effect of adding succinate, acetate, or formate as an exogenous electron donor. PA removal rates were increased by 15 and 30% for initial PA concentrations of 0.3 and 0.6 mM when 0.15 and 0.30 mM succinate, respectively, were added as exogenous electron donor. The same electron-equivalent additions of acetate and formate had the same acceleration impacts on PA removal. Consequently, the DMP-removal rate, even PA coexisting with DMP simultaneously, was accelerated by 37% by simultaneous addition of 0.3 mM succinate. Thus, lowering the accumulation of PA by addition of an electron increased the rate of DMP biodegradation.

  13. Temporal evolution of the electric field accelerating electrons away from the auroral ionosphere.

    PubMed

    Marklund, G T; Ivchenko, N; Karlsson, T; Fazakerley, A; Dunlop, M; Lindqvist, P A; Buchert, S; Owen, C; Taylor, M; Vaivalds, A; Carter, P; André, M; Balogh, A

    2001-12-13

    The bright night-time aurorae that are visible to the unaided eye are caused by electrons accelerated towards Earth by an upward-pointing electric field. On adjacent geomagnetic field lines the reverse process occurs: a downward-pointing electric field accelerates electrons away from Earth. Such magnetic-field-aligned electric fields in the collisionless plasma above the auroral ionosphere have been predicted, but how they could be maintained is still a matter for debate. The spatial and temporal behaviour of the electric fields-a knowledge of which is crucial to an understanding of their nature-cannot be resolved uniquely by single satellite measurements. Here we report on the first observations by a formation of identically instrumented satellites crossing a beam of upward-accelerated electrons. The structure of the electric potential accelerating the beam grew in magnitude and width for about 200 s, accompanied by a widening of the downward-current sheet, with the total current remaining constant. The 200-s timescale suggests that the evacuation of the electrons from the ionosphere contributes to the formation of the downward-pointing magnetic-field-aligned electric fields. This evolution implies a growing load in the downward leg of the current circuit, which may affect the visible discrete aurorae.

  14. Mitral valve-sparing procedures and prosthetic heart valve failure: A case report

    PubMed Central

    Khan, Nasir A; Butany, Jagdish; Leong, Shaun W; Rao, Vivek; Cusimano, Robert J; Ross, Heather J

    2009-01-01

    Prosthetic heart valve dysfunction due to thrombus or pannus formation can be a life-threatening complication. The present report describes a 47-year-old woman who developed valvular cardiomyopathy after chorda-sparing mitral valve replacement, and subsequently underwent heart transplantation for progressive heart failure. The explanted mitral valve prosthesis showed significant thrombus and pannus leading to reduced leaflet mobility and valvular stenosis. The present report illustrates the role of the subvalvular apparatus and pannus in prosthesis dysfunction. PMID:19279993

  15. Graphene-assisted room-temperature synthesis of 2D nanostructured hybrid electrode materials: dramatic acceleration of the formation rate of 2D metal oxide nanoplates induced by reduced graphene oxide nanosheets.

    PubMed

    Sung, Da-Young; Gunjakar, Jayavant L; Kim, Tae Woo; Kim, In Young; Lee, Yu Ri; Hwang, Seong-Ju

    2013-05-27

    A new prompt room temperature synthetic route to 2D nanostructured metal oxide-graphene-hybrid electrode materials can be developed by the application of colloidal reduced graphene oxide (RGO) nanosheets as an efficient reaction accelerator for the synthesis of δ-MnO2 2D nanoplates. Whereas the synthesis of the 2D nanostructured δ-MnO2 at room temperature requires treating divalent manganese compounds with persulfate ions for at least 24 h, the addition of RGO nanosheet causes a dramatic shortening of synthesis time to 1 h, underscoring its effectiveness for the promotion of the formation of 2D nanostructured metal oxide. To the best of our knowledge, this is the first example of the accelerated synthesis of 2D nanostructured hybrid material induced by the RGO nanosheets. The observed acceleration of nanoplate formation upon the addition of RGO nanosheets is attributable to the enhancement of the oxidizing power of persulfate ions, the increase of the solubility of precursor MnCO3, and the promoted crystal growth of δ-MnO2 2D nanoplates. The resulting hybridization between RGO nanosheets and δ-MnO2 nanoplates is quite powerful not only in increasing the surface area of manganese oxide nanoplate but also in enhancing its electrochemical activity. Of prime importance is that the present δ-MnO2 -RGO nanocomposites show much superior electrode performance over most of 2D nanostructured manganate systems including a similar porous assembly of RGO and layered MnO2 nanosheets. This result underscores that the present RGO-assisted solution-based synthesis can provide a prompt and scalable method to produce nanostructured hybrid electrode materials. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Covariant Uniform Acceleration

    NASA Astrophysics Data System (ADS)

    Friedman, Yaakov; Scarr, Tzvi

    2013-04-01

    We derive a 4D covariant Relativistic Dynamics Equation. This equation canonically extends the 3D relativistic dynamics equation , where F is the 3D force and p = m0γv is the 3D relativistic momentum. The standard 4D equation is only partially covariant. To achieve full Lorentz covariance, we replace the four-force F by a rank 2 antisymmetric tensor acting on the four-velocity. By taking this tensor to be constant, we obtain a covariant definition of uniformly accelerated motion. This solves a problem of Einstein and Planck. We compute explicit solutions for uniformly accelerated motion. The solutions are divided into four Lorentz-invariant types: null, linear, rotational, and general. For null acceleration, the worldline is cubic in the time. Linear acceleration covariantly extends 1D hyperbolic motion, while rotational acceleration covariantly extends pure rotational motion. We use Generalized Fermi-Walker transport to construct a uniformly accelerated family of inertial frames which are instantaneously comoving to a uniformly accelerated observer. We explain the connection between our approach and that of Mashhoon. We show that our solutions of uniformly accelerated motion have constant acceleration in the comoving frame. Assuming the Weak Hypothesis of Locality, we obtain local spacetime transformations from a uniformly accelerated frame K' to an inertial frame K. The spacetime transformations between two uniformly accelerated frames with the same acceleration are Lorentz. We compute the metric at an arbitrary point of a uniformly accelerated frame. We obtain velocity and acceleration transformations from a uniformly accelerated system K' to an inertial frame K. We introduce the 4D velocity, an adaptation of Horwitz and Piron s notion of "off-shell." We derive the general formula for the time dilation between accelerated clocks. We obtain a formula for the angular velocity of a uniformly accelerated object. Every rest point of K' is uniformly accelerated, and

  17. Bone formation is not impaired by hibernation (disuse) in black bears Ursus americanus

    USGS Publications Warehouse

    Donahue, S.W.; Vaughan, M.R.; Demers, L.M.; Donahue, H.J.

    2003-01-01

    Disuse by bed rest, limb immobilization or space flight causes rapid bone loss by arresting bone formation and accelerating bone resorption. This net bone loss increases the risk of fracture upon remobilization. Bone loss also occurs in hibernating ground squirrels, golden hamsters, and little brown bats by arresting bone formation and accelerating bone resorption. There is some histological evidence to suggest that black bears Ursus americanus do not lose bone mass during hibernation (i.e. disuse). There is also evidence suggesting that muscle mass and strength are preserved in black bears during hibernation. The question of whether bears can prevent bone loss during hibernation has not been conclusively answered. The goal of the current study was to further assess bone metabolism in hibernating black bears. Using the same serum markers of bone remodeling used to evaluate human patients with osteoporosis, we assayed serum from five black bears, collected every 10 days over a 196-day period, for bone resorption and formation markers. Here we show that bone resorption remains elevated over the entire hibernation period compared to the pre-hibernation period, but osteoblastic bone formation is not impaired by hibernation and is rapidly accelerated during remobilization following hibernation.

  18. Morusinol extracted from Morus alba inhibits arterial thrombosis and modulates platelet activation for the treatment of cardiovascular disease.

    PubMed

    Lee, Jung-Jin; Yang, Hyun; Yoo, Yeong-Min; Hong, Seong Su; Lee, Dongho; Lee, Hyun-Jung; Lee, Hak-Ju; Myung, Chang-Seon; Choi, Kyung-Chul; Jeung, Eui-Bae

    2012-01-01

    Morus alba (white mulberry) has been used in traditional Chinese medicine as an anti-headache, diuretic, expectorant, and anti-diabetic agent. In previous studies, extracts of Morus alba demonstrated favorable biological properties, such as antioxidant activity, suppression of lipoxygenase (LOX)-1, cytotoxicity against cancer cells, and inhibition of the invasion and migration of cancer cells. This study further evaluated the effects of morusinol, a flavonoid derived from Morus alba root bark, on platelet aggregation and thromboxane B(2) (TXB(2) formation in vitro and thrombus formation in vivo. The antiplatelet potential of morusinol was measured using in vitro rabbit platelet aggregation and TXB(2) formation assays. Arterial thrombus formation was investigated using an in vivo ferric chloride (FeCl(3)-induced thrombosis model. Morusinol significantly inhibited collagen- and arachidonic acid-induced platelet aggregation and TXB(2) formation in cultured platelets in a concentration-dependent manner. Thrombus formation was reduced by 32.1, 42.0, and 99.0% for collagen-induced TXB(2) formation, and 8.0, 24.1, and 29.2% for arachadonic acid-induced TXB(2) formation, with 5, 10, and 30 µg/mL morusinol, respectively. Moreover, oral morusinol (20 mg/kg) or aspirin (20 mg/kg) for three days significantly increased the time to occlusion in vivo by 20.3±5.0 or 6.8±2.9 min, respectively, compared with the control (1% CMC, carboxymethyl cellulose). Taken together, these results indicate that morusinol may significantly inhibit arterial thrombosis in vivo due to antiplatelet activity. Thus, morusinol may exert beneficial effects on transient ischemic attacks or stroke via the modulation of platelet activation.

  19. Analyzing radial acceleration with a smartphone acceleration sensor

    NASA Astrophysics Data System (ADS)

    Vogt, Patrik; Kuhn, Jochen

    2013-03-01

    This paper continues the sequence of experiments using the acceleration sensor of smartphones (for description of the function and the use of the acceleration sensor, see Ref. 1) within this column, in this case for analyzing the radial acceleration.

  20. Coherex WAVECREST I Left Atrial Appendage Occlusion Study

    ClinicalTrials.gov

    2015-01-13

    Non-valvular Paroxysmal, Persistent, or Permanent Atrial Fibrillation; LAA Anatomy Amenable to Treatment by Percutaneous Technique; Anticoagulation Indication for Potential Thrombus Formation in the Left Atrium